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Evidence Against RAB 40 AL Being the Locus for M artin– P robst X ‐Linked Deafness–Intellectual Disability Syndrome
Author(s) -
Ołdak Monika,
Ścieżyńska Aneta,
Młynarski Wojciech,
Borowiec Maciej,
Ruszkowska Ewelina,
Szulborski Kamil,
Pollak Agnieszka,
Kosińska Joanna,
MuellerMalesińska Małgorzata,
Stawiński Piotr,
Szaflik Jacek P.,
Płoski Rafał
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22620
Subject(s) - missense mutation , biology , exome sequencing , genetics , locus (genetics) , intellectual disability , allele , asymptomatic , exome , dna sequencing , population , disease , fragile x syndrome , gene , mutation , medicine , environmental health
RAB 40 AL has been reported as the locus for M artin– P robst syndrome ( MPS ), an X ‐linked deafness–intellectual disability syndrome. The report was based on segregation of a missense change p. D 59 G with the disease in a single family and in vitro localization studies. We found the p. D 59 G variant by whole‐exome sequencing in two patients; however, the diagnosis of MPS was excluded in both cases. Furthermore, screening of control DNA samples ( n = 810) from a general P olish population, using allele‐specific PCR and direct DNA sequencing for verification, identified p. D 59 G in 8/405 males and 12/405 females. High prevalence of the p. D 59 G variant (2.47%) is typical for a common genetic variation observed in asymptomatic individuals. Our data question the role of RAB 40 AL mutation as a disease‐causing change and the involvement of RAB 40 AL in MPS . Considering an increasing use of next‐generation sequencing in the clinical setting, our finding is of practical diagnostic importance.