A note of caution on the diagnosis of Martin-Probst syndrome by the detection of the p.D59G mutation in the RAB40AL gene

作者：Oldak Monika^*; Ruszkowska Ewelina; Pollak Agnieszka; Sobczyk Kopciol Agnieszka; Kowalewski Cezary; Piwonska Aleksandra; Drygas Wojciech; Ploski Rafal

来源：European Journal of Pediatrics, 2015, 174(5): 693-696.

DOI：10.1007/s00431-014-2452-x

• RAB40AL
• p.D59G
• Mutation
• Martin-Probst syndrome
• Whole exome sequencing

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.
Conclusion: 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.

• 出版日期2015-5