Germline mutations in retinoma patients: relevance to low-penetrance and low-expressivity molecular basis.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_2FAE5A82FC9F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Germline mutations in retinoma patients: relevance to low-penetrance and low-expressivity molecular basis.
Périodique
Molecular Vision
Auteur(s)
Abouzeid H., Schorderet D.F., Balmer A., Munier F.L.
ISSN
1090-0535[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
15
Pages
771-777
Langue
anglais
Résumé
PURPOSE: To study phenotype-genotype correlation in patients who have retinoma, which is a benign tumor resembling the post irradiation regression pattern of retinoblastoma (RB). METHODS: We selected patients who had retinoma and positive family history for RB and patients who had retinoma in one eye and either retinoma or RB in the other eye. The study included 22 patients with available DNA: 18 from 11 families and four sporadic cases. DNA was extracted from peripheral blood leukocytes. The RB1 gene was screened by DHPLC and direct sequencing of the promoter and all the exons. RESULTS: We identified 17 occurrences of 11 distinct germline mutations in two sporadic and in 15 familial cases (nine families). The 11 identified mutations were located in exons 1, 10,11,13,14, and 19 to 23. Four of the identified mutations were not previously reported, including g.64407delT, g.153236A>T, g.156743delTCTG, and g.162078delA. Eight out the 11 mutations were truncating and three were nontruncating (missense). There was no correlation between the type of mutation and the number of tumor foci per eye (RB or retinomas). Highly heterogeneous intrafamilial expressivity was observed. CONCLUSIONS: To our knowledge, this study is the largest series of mutations of consecutive retinoma patients. The present data suggest that the type of inherited mutations underlying retinoma is undistinguishable from RB related ones, i.e., largely dominated by truncating mutants. This finding is in contrast with the RB1 genotypic spectrum of mutations associated with low-penetrance RB, i.e., nontruncating mutants. The molecular mechanism underlying low-penetrance and attenuated expressivity (retinomas) appeared to be distinct.
Mots-clé
Adolescent, Adult, Child, Child, Preschool, Female, Germ-Line Mutation, Humans, Infant, Male, Middle Aged, Pedigree, Penetrance, Retinal Neoplasms/genetics, Retinoblastoma/genetics, Retinoblastoma Protein/genetics
Pubmed
Web of science
Création de la notice
03/09/2009 9:22
Dernière modification de la notice
20/08/2019 13:14
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