Pseudo low penetrance in retinoblastoma. Fortuitous familial aggregation of sporadic cases caused by independently derived mutations in two large pedigrees

Détails

ID Serval
serval:BIB_33926D26CB76
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Pseudo low penetrance in retinoblastoma. Fortuitous familial aggregation of sporadic cases caused by independently derived mutations in two large pedigrees
Périodique
Archives of Ophthalmology
Auteur(s)
Munier  F. L., Wang  M. X., Spence  M. A., Thonney  F., Balmer  A., Pescia  G., Donoso  L. A., Murphree  A. L.
ISSN
0003-9950 (Print)
Statut éditorial
Publié
Date de publication
11/1993
Volume
111
Numéro
11
Pages
1507-11
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov
Résumé
OBJECTIVE: The disparate occurrence of few cases of retinoblastoma in the same extended pedigree confronts us with the unsolved problem of a low-penetrant autosomal-dominant trait vs fortuitous familial aggregation of sporadic cases. Determination as to whether the disease arises from a common inherited mutation or sporadic mutations has important implications for genetic counseling. This is illustrated in this report of two presumed low-penetrant retinoblastoma pedigrees characterized by two distantly affected relatives connected through apparently healthy carriers. DESIGN: We mathematically modeled the inheritance patterns and calculated the a priori relative probabilities of heredity with low penetrance vs chance occurrence of independent mutations for each pedigree. The derived odds clearly show that the disease, which occurred twice in each family, most likely resulted from unrelated mutations. To prove this, extensive DNA testing was conducted, including determination of intragenic RB1 DNA sequence polymorphisms and screening for mutation using the polymerase chain reaction coupled with single-strand conformation polymorphism analysis. PATIENTS: All living key members from both pedigrees were included. RESULTS: Consistent with our initial expectation, there was no common intragenic haplotype or common germ-line mutation that segregated with the disease phenotype in either of these two families. CONCLUSIONS: We therefore conclude that collateral incidence of retinoblastoma in these two pedigrees occurred by chance and not according to autosomal-dominant inheritance with low penetrance. Furthermore, our data provide the first evidence, to our knowledge, that related individuals may have independent mutations involving an identical gene locus, giving rise to an artefactual inheritance pattern.
Mots-clé
Child, Preschool DNA, Neoplasm/genetics Eye Neoplasms/*genetics Female Genes, Retinoblastoma Humans Infant Linkage (Genetics)/genetics Male Models, Biological *Mutation Pedigree Polymerase Chain Reaction Polymorphism, Genetic Probability Retinoblastoma/*genetics
Pubmed
Web of science
Création de la notice
28/01/2008 13:53
Dernière modification de la notice
20/08/2019 14:19
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