Independent constitutional germline mutations occurring in the RB1 gene in cousins with bilateral retinoblastoma

B. Bia, J. K. Cowell

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The inheritance of a genetic susceptibility to the development of retinoblastoma generally follows an autosomal mode of inheritance with high penetrance. Rare families, however, show evidence of incomplete, penetrance where individuals can transmit the mutant gene without being affected themselves. In these families formal proof of this dogma requires the identification of the predisposing mutation. In this study we have identified the mutations in cousins with bilateral (hereditary) disease. Using SSCP and DNA sequencing, different constitutional mutations were detected in the affected cousins in this pedigree. One cousin carries a C→T mutation in exon 8 generating a stop codon directly which was also present in his affected mother whereas the other cousin carries an 8 base pair deletion in exon 20. Neither half of the family carried the same mutation as the other. The mother of the patient with the 8 bp deletion carried neither of the mutations. Thus, we have demonstrated that the retinoblastomas in this family have developed as a result of independent, sporadic genetic events which occurred coincidentally in the same extended family rather than being due to a common mutation which manifests as incompletely penetrant. These observations have important implications for genetic counselling in this type of family.

Original languageEnglish (US)
Pages (from-to)977-979
Number of pages3
JournalOncogene
Volume11
Issue number5
StatePublished - Jan 1 1995

Fingerprint

Retinoblastoma
Germ-Line Mutation
Mutation
Genes
Penetrance
Exons
Mothers
Single-Stranded Conformational Polymorphism
Inborn Genetic Diseases
Terminator Codon
Genetic Counseling
Pedigree
Genetic Predisposition to Disease
DNA Sequence Analysis
Base Pairing

Keywords

  • Mutations
  • RB1 gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Independent constitutional germline mutations occurring in the RB1 gene in cousins with bilateral retinoblastoma. / Bia, B.; Cowell, J. K.

In: Oncogene, Vol. 11, No. 5, 01.01.1995, p. 977-979.

Research output: Contribution to journalArticle

@article{ded1acae0e0b4fcda5ae0266e1b8cd2e,
title = "Independent constitutional germline mutations occurring in the RB1 gene in cousins with bilateral retinoblastoma",
abstract = "The inheritance of a genetic susceptibility to the development of retinoblastoma generally follows an autosomal mode of inheritance with high penetrance. Rare families, however, show evidence of incomplete, penetrance where individuals can transmit the mutant gene without being affected themselves. In these families formal proof of this dogma requires the identification of the predisposing mutation. In this study we have identified the mutations in cousins with bilateral (hereditary) disease. Using SSCP and DNA sequencing, different constitutional mutations were detected in the affected cousins in this pedigree. One cousin carries a C→T mutation in exon 8 generating a stop codon directly which was also present in his affected mother whereas the other cousin carries an 8 base pair deletion in exon 20. Neither half of the family carried the same mutation as the other. The mother of the patient with the 8 bp deletion carried neither of the mutations. Thus, we have demonstrated that the retinoblastomas in this family have developed as a result of independent, sporadic genetic events which occurred coincidentally in the same extended family rather than being due to a common mutation which manifests as incompletely penetrant. These observations have important implications for genetic counselling in this type of family.",
keywords = "Mutations, RB1 gene",
author = "B. Bia and Cowell, {J. K.}",
year = "1995",
month = "1",
day = "1",
language = "English (US)",
volume = "11",
pages = "977--979",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Independent constitutional germline mutations occurring in the RB1 gene in cousins with bilateral retinoblastoma

AU - Bia, B.

AU - Cowell, J. K.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - The inheritance of a genetic susceptibility to the development of retinoblastoma generally follows an autosomal mode of inheritance with high penetrance. Rare families, however, show evidence of incomplete, penetrance where individuals can transmit the mutant gene without being affected themselves. In these families formal proof of this dogma requires the identification of the predisposing mutation. In this study we have identified the mutations in cousins with bilateral (hereditary) disease. Using SSCP and DNA sequencing, different constitutional mutations were detected in the affected cousins in this pedigree. One cousin carries a C→T mutation in exon 8 generating a stop codon directly which was also present in his affected mother whereas the other cousin carries an 8 base pair deletion in exon 20. Neither half of the family carried the same mutation as the other. The mother of the patient with the 8 bp deletion carried neither of the mutations. Thus, we have demonstrated that the retinoblastomas in this family have developed as a result of independent, sporadic genetic events which occurred coincidentally in the same extended family rather than being due to a common mutation which manifests as incompletely penetrant. These observations have important implications for genetic counselling in this type of family.

AB - The inheritance of a genetic susceptibility to the development of retinoblastoma generally follows an autosomal mode of inheritance with high penetrance. Rare families, however, show evidence of incomplete, penetrance where individuals can transmit the mutant gene without being affected themselves. In these families formal proof of this dogma requires the identification of the predisposing mutation. In this study we have identified the mutations in cousins with bilateral (hereditary) disease. Using SSCP and DNA sequencing, different constitutional mutations were detected in the affected cousins in this pedigree. One cousin carries a C→T mutation in exon 8 generating a stop codon directly which was also present in his affected mother whereas the other cousin carries an 8 base pair deletion in exon 20. Neither half of the family carried the same mutation as the other. The mother of the patient with the 8 bp deletion carried neither of the mutations. Thus, we have demonstrated that the retinoblastomas in this family have developed as a result of independent, sporadic genetic events which occurred coincidentally in the same extended family rather than being due to a common mutation which manifests as incompletely penetrant. These observations have important implications for genetic counselling in this type of family.

KW - Mutations

KW - RB1 gene

UR - http://www.scopus.com/inward/record.url?scp=0029142469&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029142469&partnerID=8YFLogxK

M3 - Article

C2 - 7675457

AN - SCOPUS:0029142469

VL - 11

SP - 977

EP - 979

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 5

ER -