A note of caution on the diagnosis of Martin-Probst syndrome by the detection of the p.D59G mutation in the RAB40AL gene
| Autor: | Wojciech Drygas, Monika Ołdak, Agnieszka Sobczyk-Kopcioł, Rafał Płoski, Aleksandra Piwońska, Cezary Kowalewski, Agnieszka Pollak, Ewelina Ruszkowska |
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| Jazyk: | angličtina |
| Předmět: |
Adult
Male Pediatrics medicine.medical_specialty Hearing loss Hearing Loss Sensorineural Short Communication RAB40AL Martin-Probst syndrome Mitochondrial Proteins Neurodevelopmental disorder Intellectual Disability Genetic variation Intellectual disability medicine Humans Abnormalities Multiple Genetic Testing Pediatrics Perinatology and Child Health Genotyping Exome sequencing Genetic testing Genetics medicine.diagnostic_test business.industry Whole exome sequencing Genetic Variation Genetic Diseases X-Linked medicine.disease Pediatrics Perinatology and Child Health Mutation (genetic algorithm) Mutation ras Proteins p.D59G Female Poland medicine.symptom business |
| Zdroj: | European Journal of Pediatrics |
| ISSN: | 0340-6199 |
| DOI: | 10.1007/s00431-014-2452-x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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