Recessive truncating @entity32855 mutations presenting as XXXX .

@entity1 @entity649 @entity16 @entity32855 @entity4148 @entity2057
OBJECTIVE: To identify the cause of @entity16 in a cohort of @entity1 with genetically unsolved @entity16 (57 families with a total of 74 members) in whom hitherto known disease genes had been excluded. METHODS: We used autozygosity mapping or haplotype analysis to delineate potential disease loci in informative families. For mutation detection, we used either whole-exome sequencing or Sanger sequencing of positional candidates. Subsequently, a larger cohort was specifically screened for @entity32855 mutations. The pathogenicity of a splice-site mutation was verified in cultured @entity1 skin fibroblasts on the messenger RNA level and by Western blot. RESULTS: We report on 5 @entity1 with @entity16 from 3 families who carried truncating mutations in @entity32855 . Contrary to the "classic" phenotype, they did not manifest with @entity649 , but with progressive @entity16 . Only one @entity1 required nocturnal mask ventilation, while 4 others maintained normal respiratory function by the age of 14, 18, 22, and 37 years. Three @entity1 were still able to walk independently. All @entity1 had a predominantly @entity16 with subsequent @entity2057 , but without obvious sensory symptoms. Two @entity1 had signs of @entity4148 . CONCLUSIONS: Mutations in @entity32855 should be considered in the molecular genetic workup of @entity1 with @entity16 , even in the absence of respiratory symptoms.
