title: A note of caution on the diagnosis of Martin-Probst syndrome by the detection of the p.D59G mutation in the RAB40AL gene.
abstract: Martin-Probst syndrome (MPS) is an X-linked multisystem neurodevelopmental disorder, reported to be caused by the p.D59G mutation in RAB40AL. Whereas evidence against the pathogenic role of p.D59G has been published, the presence of RAB40AL p.D59G continues to be used as a support for MPS diagnosis. Our purpose was to provide further arguments for excluding pathogenicity of RAB40AL p.D59G. We detected p.D59G in two healthy males ascertained as family members of p.D59G carriers who underwent whole exome sequencing for diagnostic reasons. Furthermore, we found that p.D59G was present in 2.86% (4/140) of randomly selected Polish males with higher education.
  
  
  CONCLUSIONS
  Our findings are inconsistent with a causative effect of RAB40AL p.D59G on cognitive impairment combined with severe to profound bilateral hearing loss but indicate that p.D59G is a common genetic variation. Our data emphasize the need for genotyping large sample sizes of diverse populations as a basic tool in determining variant pathogenicity.
authors.affiliation: Department of Genetics, Institute of Physiology and Pathology of Hearing, Mokra 17, Kajetany, 05-830, Nadarzyn, Poland, m.oldak@ifps.org.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Ołdak
authors.forename: Ewelina
authors.initials: E
authors.lastname: Ruszkowska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pollak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Sobczyk-Kopcioł
authors.forename: Cezary
authors.initials: C
authors.lastname: Kowalewski
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Piwońska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Drygas
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D000328:Adult; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis* / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011044:Poland; D018631:ras Proteins / Q000235:genetics*
chemical_list: D024101:Mitochondrial Proteins; C466300:RAB40AL protein, human; D018631:ras Proteins