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Dommering CJ, Garvelink MM, Moll AC, et al.
Reproductive behavior of individuals with increased risk of having a child with retinoblastoma.
Clin Genet. 2012; 81(3):216-23 [PubMed] Related Publications
To investigate reproductive behavior of individuals at increased risk of having a child with retinoblastoma (Rb), we conducted a cross-sectional questionnaire survey among 118 counselees visiting the Clinical Genetics Department of the National Rb Center in the Netherlands. The recurrence risk for counselees ranged from <1% to 50%. The response rate was 69%. Of 43 respondents considering having children after becoming aware of their increased risk, Rb influenced reproductive behavior for 25 (58%), of whom 14 had a recurrence risk <3%. Twenty of these 25 decided against having more children and 5 used prenatal diagnosis. Eighteen of the 43 respondents did not use any of the alternative reproductive options and had children (or more children), although half indicated having had doubts about their decisions. Multiple logistic regression showed that only perceived risk (p = 0.003) was significantly associated with Rb influencing reproductive behavior. Of 17 respondents planning children (or more children), 11 (65%) considered using one of the alternative reproductive options. We conclude that reproductive behavior is greatly influenced by Rb and that perceived risk, not objective risk, is the most important factor of influence. It is important to offer individuals at increased risk continued access to genetic counseling, even when this risk is small.

Related: Retinoblastoma


Castéra L, Gauthier-Villars M, Dehainault C, et al.
Mosaicism in clinical practice exemplified by prenatal diagnosis in retinoblastoma.
Prenat Diagn. 2011; 31(11):1106-8 [PubMed] Related Publications


Related: Retinoblastoma RB1


Serrano C, Alonso J, Gómez-Mariano G, et al.
Low penetrance hereditary retinoblastoma in a family: what should we consider in the genetic counselling process and follow up?
Fam Cancer. 2011; 10(3):617-21 [PubMed] Related Publications
Hereditary retinoblastoma (Rb) is a high penetrance autosomal dominant disease showing not only an increased risk of suffering bilateral Rb but also other second neoplasms. However, some families show a low-penetrance phenotype with reduced expressivity and incomplete penetrance of the retinoblastoma gene (RB1). Given the lack of specific guidelines for the follow-up of adult patients with hereditary Rb, the authors present a case report of a family with a low-penetrance phenotype and review the recommended surveillance in this setting, stressing the difficulties found in the genetic counselling process and follow up. Thus, since patients are at an increased risk, lifelong regular medical surveillance to detect any second malignancy at a stage that can be cured is required. In addition, avoidance of DNA-damaging agents and genetic testing should be considered for a throughout management of these families.

Related: Retinoblastoma RB1


Dommering CJ, van den Heuvel MR, Moll AC, et al.
Reproductive decision-making: a qualitative study among couples at increased risk of having a child with retinoblastoma.
Clin Genet. 2010; 78(4):334-41 [PubMed] Related Publications
Little is known about the reproductive decision-making process of couples with an increased risk of having a child with retinoblastoma (Rb). A qualitative study was conducted to explore the impact of prospective risk on reproductive decisions, factors influencing these decisions, and the needs of couples with regard to reproductive counselling. Fourteen couples of childbearing age who received genetic counselling between 2002 and 2006 participated in semi-structured interviews in 2008. The risk of having a child with Rb ranged from less than 1% to 50%. In most cases, the diagnosis of Rb influenced subsequent family planning. Prenatal diagnosis was used by two couples, while others refrained from having more children. Reproductive decisions were influenced by the burden of the disease for the patient and family members, the impact of ophthalmological screening under anaesthesia, and couples' perceived risk, which did not always relate to their actual risk. Reproductive choices with regard to the number of children wanted changed over time. Our findings indicate topics to be discussed during genetic counselling of couples at increased risk for a child with Rb. We suggest continued access to genetic counselling also after the initial diagnosis and treatment.

Related: Retinoblastoma


Parma DL, Dalamon VK, Fernández C, et al.
[The relevance of molecular biology studies in the genetic counselling of Argentine retinoblastoma families].
Arch Soc Esp Oftalmol. 2009; 84(11):557-62 [PubMed] Related Publications
OBJECTIVE: Evaluate the relevance of RB1 mutations detection in the genetic counselling of Argentine retinoblastoma families.
METHODS: We included in this study 34 Argentine families with bilateral and unilateral Retinoblastoma (Rb). 130 DNA samples from leukocytes, tumors and chorionic villus were analyzed by indirect and direct molecular biology assays like Southern blot, segregation of polymorphisms BamHI, Rbi4, XbaI y Rb 1.20 (PCR-RFLP, PCR-STR), PCR-heteroduplex and sequencing of RB1 gene.
RESULTS: Molecular biology analysis was informative in 18 out of 34 families studied (53%), 56% with bilateral and 44% with unilateral Rb. DNA tumor samples of 11 patients were available and could be studied by loss of heterozygosity (LOH) detection, that allowed us to identify the mutated RB1 allele in 9 (82%) patients. When tumor samples were not analized, the studies were informative only in 9 out of 23 patients (39%); we used direct mutation detection in 17 (41% informative) and indirect assays in 20 (60% informative) patients.
CONCLUSIONS: The results prove the necessity to have DNA tumor, when the patient has been enucleated, and emphasize the importance of direct mutation detection in families with early sporadic Rb without tumor sample. The RB1 molecular biology contributed to the adequate genetic counselling of Argentine patients and relatives and their appropriate early treatment planning (Arch Soc Esp Oftalmol 2009; 84: 557-562).

Related: Retinoblastoma RB1


Barbosa RH, Vargas FR, Lucena E, et al.
Constitutive RB1 mutation in a child conceived by in vitro fertilization: implications for genetic counseling.
BMC Med Genet. 2009; 10:75 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The purpose of this study was to identify mutations associated with bilateral retinoblastoma in a quadruplet conceived by in vitro fertilization, and to trace the parental origin of mutations in the four quadruplets and their father.
METHODS: Mutational screening was carried out by sequencing. Genotyping was carried out for determining quadruplet zygosity.
RESULTS: The proband was a carrier of a novel RB1 constitutive mutation (g.2056C>G) which was not detected in her father or her unaffected sisters, and of two other mutations (g.39606 C>T and g.174351T>A) also present in two monozygotic sisters. The novel mutation probably occurred de novo while the others were of likely maternal origin. The novel mutation, affecting the Kozak consensus at the 5'UTR of RB1 and g.174351T>A were likely associated to retinoblastoma in the proband.
CONCLUSION: Molecular diagnosis of retinoblastoma requires genotypic data of the family for determining hereditary transmission. In the case of children generated by IVF with oocytes from an anonymous donor which had been stored in a cell repository, this might not be successfully accomplished, making precise diagnosis impracticable for genetic counseling.

Related: Chromosome 13 Retinoblastoma RB1


MacCarthy A, Birch JM, Draper GJ, et al.
Retinoblastoma in Great Britain 1963-2002.
Br J Ophthalmol. 2009; 93(1):33-7 [PubMed] Related Publications
AIM: This paper describes the epidemiology and family history status of 1601 children with retinoblastoma in Great Britain diagnosed 1963-2002 and summarises the practical consequences for diagnosis and counselling of developments in molecular genetics.
METHODS: Incidence rates were analysed according to year of diagnosis and tumour laterality. Cases were classified as heritable or non-heritable on the basis of laterality and family history of the disease.
RESULTS: There were 998 unilateral cases, 581 bilateral and 22 of unknown laterality. Bilateral cases tended to be diagnosed at a younger age than unilateral. All bilateral cases are regarded as heritable, and 35% had a family history of the disease. 7% of the unilateral cases had a family history and are therefore heritable. Thus, at least (41%) of our cases are heritable. This is an underestimate, since these data on family history are incomplete. For unilateral cases aged below 1 year, the reported incidence rate increased significantly (p<0.0001) by about 2.5% per year; for the age group 1-4 years, the average increase was about 0.5% per year (not significant).

Related: Retinoblastoma


Barbosa RH, Vargas FR, Aguiar FC, et al.
Hereditary retinoblastoma transmitted by maternal germline mosaicism.
Pediatr Blood Cancer. 2008; 51(5):598-602 [PubMed] Related Publications
BACKGROUND: Investigating transmission of a constitutive, g78238C > T (R552X), RB1 mutation in four affected children descended from three different unaffected fathers and an unaffected mother.
PROCEDURES: Sequence data analyses and allele-specific PCR assays were used to investigate the presence of the mutation in four affected children, five unaffected sibs (or half-sibs), and the unaffected mother. Haplotyping was carried out for confirming that the children descended from different fathers.
RESULTS: Haplotyping excluded the possibility of paternal transmission of a de novo mutation and provided evidence of maternal germline mosaicism. The mutation was apparently absent in blood- and buccal cell-DNA of the mother who also showed a normal fundoscopy.
CONCLUSIONS: Our findings indicated that mosaicism was restricted to the maternal germline. The mutational event must have occurred at least 4 weeks post-conception, unlike the early mutational events of most mosaics, occurring between fertilization and the 8th day of conception. The implications of these findings are discussed in view that genetic counselling should discriminate between germline mosaicism and de novo events in pseudo-low-penetrant hereditary retinoblastoma.

Related: Retinoblastoma RB1


Clarke SA, Sheppard L, Eiser C
Mothers' explanations of communicating past health and future risks to survivors of childhood cancer.
Clin Child Psychol Psychiatry. 2008; 13(1):157-70 [PubMed] Related Publications
Mothers of survivors of Retinoblastoma (Rb) experience unique challenges communicating with their child about the condition. Children are mostly diagnosed within their first year but the consequences continue into young adult life. Here 39 mothers of Rb survivors (23 males, mean age = 10.26 years) were interviewed about their experiences. Mothers were asked about communication with their children about Rb, and future health risks. Interviews were analysed using thematic analysis. Mothers reported that they had informed children about past diagnosis and treatment but had spoken less about genetic risk or risk of secondary cancer. The child's age and information-seeking behaviour were associated with mothers' disclosure, along with mothers' perceptions that information would facilitate child coping. Findings suggest that mothers may need more guidance during follow-up care in communicating about the disease and its consequences for future health. Medical staff should also take extra care to ensure that mothers are aware of genetic counselling services and how to access them before the child is discharged from specialist care.

Related: Retinoblastoma


Ramprasad VL, Madhavan J, Murugan S, et al.
Retinoblastoma in India : microsatellite analysis and its application in genetic counseling.
Mol Diagn Ther. 2007; 11(1):63-70 [PubMed] Related Publications
OBJECTIVES: This study was conducted with two objectives. The first was to estimate the frequency of loss of heterozygosity (LOH) of the RB1 gene as a mechanism in disease causation in tumors of patients from India. The second objective was to employ RB1 molecular deletion and microsatellite-based linkage analysis as laboratory tools, while counseling families with a history of retinoblastoma (RB).
METHODS: DNA was extracted from peripheral blood and tumors of 54 RB patients and their relatives. Eight fluorescent microsatellite markers, both intragenic and flanking the RB1 gene, were used. After PCR amplification, samples were run on an ABI PRISM 310 genetic analyzer for LOH, deletion detection, and haplotype generation.
RESULTS: LOH was found in conjunction with tumor formation in 72.9% of RB patients (39/54 patients; p=0.001; 95% CI 0.6028, 0.8417); however, we could not associate various other clinical parameters of RB patients with the presence or absence of RB1 LOH. Seven germline deletions (13% of RB patients) were identified, and the maternal allele was more frequently lost (p=0.01). A disease co-segregating haplotype was detected in two hereditary autosomal dominant cases.
CONCLUSION: LOH of the RB1 gene could play an important role in tumor formation. Large deletions involving RB1 were observed, and a disease co-segregating haplotype was used for indirect genetic testing. This is the first report from India where molecular testing has been applied for RB families in conjunction with genetic counseling. In tertiary ophthalmic practice in India, there is an emerging trend towards the application of genetical knowledge in clinical practice.

Related: Eye Cancer Retinoblastoma


Kontic M, Palacios I, Gámez A, et al.
New RB1 oncogenic mutations and intronic polymorphisms in Serbian retinoblastoma patients: genetic counseling implications.
J Hum Genet. 2006; 51(10):909-13 [PubMed] Related Publications
The purpose of this work was to identify germ line RB1 mutations in 16 Serbian retinoblastoma patients for genetic counselling. Mutation analysis was carried out by PCR directed sequencing of the 27 exons. Loss of heterozygosity for two RB1 intragenic markers was also analyzed in 14 tumour samples. Five new RB1 oncogenic mutations (g.2078 del C, g.77047_48 del GC, g.78117_8 del TT, g.160797 del T, and g.64439+2 T>C) and two recurrences (R445X and Q383X) have been found in this study. In addition, four intronic variants were observed germ line in some unilateral patients. Two of these variants (g.44668-15T/G, and g.166204-8T/A) are discussed as potential oncogenic mutation candidates. The results show the relevance of studies aimed to investigate the role of intronic variants in exon splicing regulation. Such studies will help to disclose hidden retinoblastoma susceptibilities, important for accurate genetic counselling.

Related: Polymorphisms Retinoblastoma RB1


Alonso J, Palacios I, Gámez A, et al.
[Molecular diagnosis of retinoblastoma: molecular epidemiology and genetic counseling].
Med Clin (Barc). 2006; 126(11):401-5 [PubMed] Related Publications
BACKGROUND AND OBJECTIVE: Retinoblastoma, a prototype of hereditary cancer, is the most common intraocular tumor in children and a potential cause of blindness from therapeutic eye ablation, second tumors in germ line mutation carriers, and even death when untreated. The molecular scanning of RB1 in search of germ line mutations in 213 retinoblastoma patients from Spain, Cuba, Colombia and Serbia, has led to the detection of 106 mutations whose knowledge is important for genetic counselling and characterization of phenotypic-genotypic relations.
PATIENTS AND METHOD: Mutational study (PCR-sequentiation and microsatellites analysis) in patients with retinoblastoma, from Spain, Cuba, Colombia and Serbia.
RESULTS: 45% of mutations, including most of the frame shift (FS), missense (MS) and splicing (SP), were new, while all nonsense mutations (NS) corresponded to hypermutable sites in RB1. Germ line mutations were found in 22% of unilateral sporadic patients. The incidence of SP plus MS mutations in this group of patients was greater (p = 0.018) than in bilateral patients. The frequency of SP mutations was higher (p = 0.0003) in Spain and France than in Germany and United Kingdom, while the incidence of NS mutations was lower (p = 0.0006). SP mutations were associated with the low penetrance phenotype and were also overrepresented (p = 0.018) in patients with delayed retinoblastoma onset.
CONCLUSIONS: Mutational scanning of unilateral patients is important for genetic counselling and may help decipher the molecular mechanisms leading to low penetrance or expressivity. The functional characterization of mutations associated with low-penetrance or expressivity phenotypes and the molecular classification of tumors using multiple expression profiling is important for a better understanding of the retinoblastoma pathogenesis.

Related: Retinoblastoma RB1


Sampieri K, Hadjistilianou T, Mari F, et al.
Mutational screening of the RB1 gene in Italian patients with retinoblastoma reveals 11 novel mutations.
J Hum Genet. 2006; 51(3):209-16 [PubMed] Related Publications
Retinoblastoma (RB, OMIM#180200) is the most common intraocular tumour in infancy and early childhood. Constituent mutations in the RB1 gene predispose individuals to RB development. We performed a mutational screening of the RB1 gene in Italian patients affected by RB referred to the Medical Genetics of the University of Siena. In 35 unrelated patients, we identified germline RB1 mutations in 6 out of 9 familial cases (66%) and in 7 out of 26 with no family history of RB (27%). Using the single-strand conformational polymorphism (SSCP) technique, 11 novel mutations were detected, including 3 nonsense, 5 frameshift and 4 splice-site mutations. Only two of these mutations (1 splice site and 1 missense) were previously reported. The mutation spectrum reflects the published literature, encompassing predominately nonsense or frameshift and splicing mutations. RB1 germline mutation was detected in 37% of our cases. Gross rearrangements outside the investigated region, altered DNA methylation, or mutations in non-coding regions, may be the cause of disease in the remainder of the patients. Some cases, e.g. a case of incomplete penetrance, or variable expressivity ranging from retinoma to multiple tumours, are discussed in detail. In addition, a case of pre-conception genetic counselling resolved by rescue of banked cordonal blood of the affected deceased child is described.

Related: Retinoblastoma


Joseph B, Shanmugam MP, Srinivasan MK, Kumaramanickavel G
Retinoblastoma: genetic testing versus conventional clinical screening in India.
Mol Diagn. 2004; 8(4):237-43 [PubMed] Related Publications
INTRODUCTION: Genetic testing is increasingly being used to evaluate susceptibility to hereditary diseases because it is a cost effective screening method. Predictive testing for retinoblastoma can help to save the vision and avoid unnecessary (and invasive) eye examinations for probands and their close relatives. This study was undertaken to evaluate the cost effectiveness of the retinoblastoma genetic screening strategy established in our hospital.
STUDY DESIGN: Cytogenetic study of peripheral blood, mutational, and methylation analyses from the tumor DNA of 25 patients with retinoblastoma was undertaken. The cost for retinoblastoma (RB1) gene screening was calculated based on the cost of the chemicals and consumables used and the clinical examination charges at our hospital. A comparison was made between the cost of genetic screening and clinical testing for retinoblastoma. Retinoblastoma patients underwent clinical management and genetic testing at Sankara Nethralaya, Chennai, India.
RESULTS: By adopting a genetic screening strategy, a 3.5-fold cost saving was seen for a proband while a 6-fold saving was seen for a family with two sibs compared to the cost of clinical examination. The clinical examination fee and cost of genetic screening for a proband was dollarUS536 and dollarUS152, respectively, while for a nuclear family with two sibs the costs were dollarUS1071 and dollarUS175, respectively.
DISCUSSION: Savings for a family will be higher if indirect costs, such as savings in travel times to and from the hospital and labor savings, were taken into account. Cost will be a major factor in determining the implementation of genetic screening for RB1 gene in the clinical practice.
CONCLUSION: In our study in India, genetic screening for retinoblastoma was cheaper than conventional screening and was useful in the genetic counseling of the families.

Related: Retinoblastoma RB1


Abramson DH, Schefler AC
Update on retinoblastoma.
Retina. 2004; 24(6):828-48 [PubMed] Related Publications


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Sugano K, Yoshida T, Izumi H, et al.
Outpatient clinic for genetic counseling and gene testing of retinoblastoma.
Int J Clin Oncol. 2004; 9(1):25-30 [PubMed] Related Publications
We report on the genetic counseling and gene testing of patients with retinoblastoma who visited the National Cancer Center Hospital, Tokyo, from April 1997 through September 2003. During this period, 73 probands visited the clinic, and gene testing was performed in 51 individuals. Germline mutations of the RBI gene were detected in 20 individuals (39%); the frequencies were 82% (9/11) in bilateral/familial retinoblastoma, 50% (2/4) in unilateral/familial retinoblastoma, 50% (8/16) in bilateral/nonfamilial retinoblastoma, and 5% (1/20) in unilateral/nonfamilial retinoblastoma. Gene testing is indicated in the medical practice of hereditary retinoblastoma for familial risk assessment, while prior counseling is important for an understanding of the risks and benefits of gene testing. With improvements in patient prognosis, counseling for adult survivors is increasing in importance. Assessment of genetic risk to the offspring and prevention of secondary cancer are the primary issues of concern. Presymptomatic diagnosis of infants is effective for the proper assessment of the genetic risk and for making follow-up schedules for the detection of the tumor at an early stage.

Related: Retinoblastoma


Munier F, Balmer A, Schorderet DF
[Diagnosis, treatment, and familial management of retinoblastoma].
Rev Med Suisse Romande. 2000; 120(5):443-7 [PubMed] Related Publications


Related: Retinoblastoma


Kostyk E, Pietrzyk JJ
[Genetic background of retinoblastoma].
Med Wieku Rozwoj. 1999 Jan-Mar; 3(1):33-40 [PubMed] Related Publications
Retinoblastoma is a malignant tumour of the eye ball, which develops as a result of the mutation of both alleles of RB-1 gene. Molecular mechanisms and their implications in clinical diagnosis and genetic counselling in retinoblastoma families are discussed.

Related: Retinoblastoma RB1


Pam VA, Mohammed I, Olali CA
Retinoblastoma in an adult: a case report.
West Afr J Med. 1998 Oct-Dec; 17(4):280-3 [PubMed] Related Publications
A case of retinoblastoma in an adult with a family history of retinoblatoma is presented. To our knowledge, this is presumably the first case of retinoblastoma recorded in an adult in Northern Nigeria. The differential diagnosis, genetics, and importance of counselling and early presentation are discussed.

Related: Retinoblastoma


Girardet A, Beaufrere L, Tuffery S, et al.
[Retinoblastoma: importance of genetic counseling].
J Fr Ophtalmol. 1998; 21(4):295-301 [PubMed] Related Publications


Related: Bone Cancers Chromosome 13 Osteosarcoma Retinoblastoma


Huang Q, Dryja TP, Yandell DW
[Gene diagnosis and genetic counselling of Rb gene mutations in retinoblastoma patients and their family members].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 1998; 15(2):65-8 [PubMed] Related Publications
OBJECTIVE: To develop a diagnostic test for direct identification of disease-causing mutation in the patients with retinoblastoma and correct prediction of carrier- status in unaffected adults and newborns in the RB kindred.
METHODS: Southern blot hybridized by Rb cDNA and other intragenic probes were used to detect big deletions or rearrangements at Rb gene locus. SSCP analysis and direct sequencing of primer-directed enzymatic amplification to identify point mutations as small as a single nucleotide change. RFLPs and VNTRs within the Rb gene were used as genetic markers for haplotype analysis.
RESULTS: The probands from 79 RB kindreds were identified to have Rb gene mutation, including 25 somatic mutations and 54 germline mutations (36 new germline mutations, 15 inherited mutations and 3 mosaicisms). The WBC DNAs from their family members were also analyzed for determining origin and carrier of mutation.
CONCLUSION: The direct identification of causing- cancer mutations by combining SSCP analysis and direct DNA sequencing showed many advantages than other indirect methods such as haplotype analysis. It can distinguish hereditary RB from nonhereditary RB and identify the unaffected carriers without family history and informes affected family member. This method is helpful in gene diagnosis and genetic counselling.

Related: Retinoblastoma


Sippel KC, Fraioli RE, Smith GD, et al.
Frequency of somatic and germ-line mosaicism in retinoblastoma: implications for genetic counseling.
Am J Hum Genet. 1998; 62(3):610-9 [PubMed] Free Access to Full Article Related Publications
Although mosaicism can have important implications for genetic counseling of families with hereditary disorders, information regarding the incidence of mosaicism is available for only a few genetic diseases. Here we describe an evaluation of 156 families with retinoblastoma; the initial oncogenic mutation in the retinoblastoma gene had been identified in these families. In 15 ( approximately 10%) families, we were able to document mosaicism for the initial mutation in the retinoblastoma gene, either in the proband or in one of the proband's parents. The true incidence of mosaicism in this group of 156 families is probably higher than our findings indicate; in some additional families beyond the 15 we identified, mosaicism was likely but could not be proven, because somatic or germ-line DNA from key family members was unavailable. Germ-line DNA from two mosaic fathers was analyzed: in one of these, the mutation was detected in both sperm and leukocyte DNA; in the other, the mutation was detected only in sperm DNA. Our data suggest that mosaicism is more common than is generally appreciated, especially in disorders such as retinoblastoma, in which a high proportion of cases represent new mutations. The possibility of mosaicism should always be considered during the genetic counseling of newly identified families with retinoblastoma. As demonstrated here, genetic tests of germ-line DNA can provide valuable information that is not available through analysis of somatic (leukocyte) DNA.

Related: Retinoblastoma


Servodidio CA, Abramson DH
Genetic teaching for the retinoblastoma patient.
Insight. 1996; 21(4):120-4; quiz 125-6 [PubMed] Related Publications
Retinoblastoma is the most common primary intraocular tumor in children. Retinoblastoma can be hereditary (familial) or nonhereditary (nonfamilial). Nurses who have an understanding of the genetic patterns for retinoblastoma can participate in the counseling of these patients. A chart is provided as a tool for teaching patients about family patterns of retinoblastoma.

Related: Retinoblastoma


Cowell JK, Cragg H
Constitutional nonsense germline mutations in the RB1 gene detected in patients with early onset unilateral retinoblastoma.
Eur J Cancer. 1996; 32A(10):1749-52 [PubMed] Related Publications
The 'two-hit' hypothesis for the development of the childhood eye cancer, retinoblastoma (Rb), predicts that bilaterally affected individuals will carry germline mutations. The second suggestion is that patients with early presentation of unilateral tumours also carry predisposing mutations. We have used SSCP analysis to study the 27 individual exons of the RB1 gene in constitutional DNA from 3 patients whose tumours were treated under the age of 12 months. Bandshifts on SSCP gels were detected in 2 of these patients which, on sequencing, were shown to be a C-->T transition converting a CGAarg to a TGAstop codon in exon 17 and an 8 bp deletion in exon 20 resulting in a downstream stop codon. The mutations seen in these patients are reminiscent of those seen in patients with hereditary Rb and confirms that at least some early onset unilateral cases carry constitutional mutations, which has important implications for genetic screening and counselling of these individuals.

Related: Eye Cancer Retinoblastoma


Munier FL, Thonney F, Balmer A, et al.
Sex mutation ratio in retinoblastoma and retinoma: relevance to genetic counseling.
Klin Monbl Augenheilkd. 1996; 208(5):400-3 [PubMed] Related Publications
PURPOSE AND METHOD: The parental origin of initial somatic and germline mutations (M1) in the retinoblastoma gene (RB1) was explored in 36 retinoblastoma (Rb) and 5 retinoma patients, of which 16 were presumably non-hereditary and 25 were hereditary. By this approach the male:female mutation ratio was determined by the gender quotient of mutation origin.
RESULTS: The male to female mutation ratio in hereditary Rb was 19:2, which is consistent with a significant bias towards paternal origin of germline mutation. This ratio was of 5:2 in non-hereditary Rb which is not significant.
DISCUSSION: Together with the published data, these results support a preferential paternal mutagenesis in hereditary Rb, but appear to reject paternal genomic imprinting at the RB1 locus as previously proposed in non-hereditary Rb. Genetic counseling in sporadic Rb may be substantially improved by the identification of the parental origin of initial mutation.

Related: Eye Cancer Retinoblastoma


Minoda K
[Genetics of retinoblastoma].
Nihon Rinsho. 1995; 53(11):2774-8 [PubMed] Related Publications
Recent advancement of molecular genetics has enabled us to perform presymptomatic prediction for hereditary retinoblastoma, based on RB gene diagnosis. We used PCR combined with SSCP and heteroduplex analysis to screen leukocyte DNA, exon by exon, in patients with bilateral retinoblastoma. Germline mutations were detected in the 22 of the 33 cases, and, in 16 cases, the mutations were identified by sequencing. Among 2 families with those hereditary retinoblastoma presymptomatic prediction by the method described above was applied for 2 newborn babies, resulting in both success. It is expected that gene diagnosis will be applied for not only bilateral but also unilateral cases for genetic counseling.

Related: Eye Cancer Retinoblastoma


Lendi B, Pescia G, Thonney F, et al.
[Clinical applications of molecular diagnosis of retinoblastoma ain 15 families].
Klin Monbl Augenheilkd. 1995; 206(5):336-8 [PubMed] Related Publications
PURPOSE: In 40% retinoblastoma (Rb) results from a hereditary mutation of the Rb susceptibility gene (RB1). In this study, we tested the usefulness of intragenic DNA analysis for ophthalmologic follow-up in affected families.
METHODS: Molecular analysis was performed on 103 DNA samples of 15 Rb families. We used 7 intragenic polymorphic markers and one within the ESD gene for mutation linkage analysis.
FINDINGS: DNA analysis was informative in 88% of relatives at risk of developing Rb. Among them, the presence of a mutated RB1 allele was excluded in 46%, while 29% were unaffected carriers and 25% had inherited the Rb predisposition.
CONCLUSION: In the majority of familial Rb, the DNA analysis allows the identification of children carrying a RB1 mutation and who will need a close ophthalmologic follow-up under general anesthesia. When the mutated gene is absent, ophthalmological examination under narcosis is unnecessary. Finally, identification of asymptomatic carriers improve the accuracy of genetic counselling.

Related: Eye Cancer Retinoblastoma


Zhang Q, Minoda K
Mutation detection and genetic counseling in retinoblastoma using heteroduplex analysis.
Jpn J Ophthalmol. 1995; 39(4):432-7 [PubMed] Related Publications
Gene diagnosis is essential for confident presymptomatic prediction, genetic counseling, and early management of hereditary retinoblastoma. In screening the leukocyte DNA of three patients with bilateral retinoblastoma for RB1-gene heterozygous germline mutations, we identified mutations involving exon 3 or 18 of the RB1 gene by using heteroduplex analysis and sequencing. In one case the mutation was a 2 bp GT deletion resulting in the loss of the exon 18 splicing-donor; another mutation was a G-to-T transversion at codon 580 in exon 18, which converts Arg to a stop codon. The third mutation involved in 1 bp deletion at codon 96 in exon 3, which leads to a premature stop codon at codon 110. We used information from this heteroduplex technique for genetic counseling and presymptomatic prediction. A newborn was identified as normal, using gene diagnosis; his 15-month follow-up confirmed our prediction.

Related: Eye Cancer Retinoblastoma


Servodidio CA, Abramson DH
Genetic teaching for the retinoblastoma patient.
Insight. 1994; 19(4):20-3, 25 [PubMed] Related Publications
Retinoblastoma is the most common primary intraocular tumor in children. Retinoblastoma can be hereditary (familial) or nonhereditary (nonfamilial). Nurses who have an understanding of the genetic patterns for retinoblastoma can participate in the counseling of these patients. A chart is provided as a tool for teaching patients about family patterns of retinoblastoma.

Related: Eye Cancer Retinoblastoma


Zajaczek S, Górski B, Débniak T, et al.
[VNTR-PCR in diagnosis of inherited Rb gene mutation].
Klin Oczna. 1994 Aug-Sep; 96(8-9):290-2 [PubMed] Related Publications
Molecular genetic analysis of DNA by PCR-VNTR was performed in a family with hereditary retinoblastoma presenting some difficulties in pedigree analysis. PCR-VNTR allowed to perform a more accurate counselling in this family. Analysis of the way of transmission, carrier status exclusion (in two persons) and confirmation (in one) was possible only by VNTR-PCR.

Related: Eye Cancer Retinoblastoma



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