title: Evidence against RAB40AL being the locus for Martin-Probst X-linked deafness-intellectual disability syndrome.
abstract: RAB40AL has been reported as the locus for Martin-Probst syndrome (MPS), an X-linked deafness-intellectual disability syndrome. The report was based on segregation of a missense change p.D59G with the disease in a single family and in vitro localization studies. We found the p.D59G 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 Polish population, using allele-specific PCR and direct DNA sequencing for verification, identified p.D59G in 8/405 males and 12/405 females. High prevalence of the p.D59G variant (2.47%) is typical for a common genetic variation observed in asymptomatic individuals. Our data question the role of RAB40AL mutation as a disease-causing change and the involvement of RAB40AL in MPS. Considering an increasing use of next-generation sequencing in the clinical setting, our finding is of practical diagnostic importance.
authors.affiliation: Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland; Institute of Physiology and Pathology of Hearing, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Ołdak
authors.forename: Aneta
authors.initials: A
authors.lastname: Ścieżyńska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Młynarski
authors.forename: Maciej
authors.initials: M
authors.lastname: Borowiec
authors.forename: Ewelina
authors.initials: E
authors.lastname: Ruszkowska
authors.forename: Kamil
authors.initials: K
authors.lastname: Szulborski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pollak
authors.forename: Joanna
authors.initials: J
authors.lastname: Kosińska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Mueller-Malesińska
authors.forename: Piotr
authors.initials: P
authors.lastname: Stawiński
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005820:Genetic Testing; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011044:Poland; D017422:Sequence Analysis, DNA; D018631:ras Proteins / Q000235:genetics*
chemical_list: D024101:Mitochondrial Proteins; C466300:RAB40AL protein, human; D018631:ras Proteins
keywords: Martin-Probst syndrome; RAB40AL; deafness; intellectual disability; nonpathogenic; whole-exome sequencing