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Phenotypic evolution of UNC80 loss of function
Author(s) -
Valkanas Elise,
Schaffer Katherine,
Dunham Christopher,
Maduro Valerie,
du Souich Christèle,
Rupps Rosemarie,
Adams David R.,
BaradaranHeravi Alireza,
Flynn Elise,
Malicdan May C.,
Gahl William A.,
Toro Camilo,
Boerkoel Cornelius F.
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37929
Subject(s) - failure to thrive , loss function , exome sequencing , nonsense , genetics , phenotype , gain of function , biology , nonsense mutation , hereditary spastic paraplegia , mutation , gene , missense mutation
Failure to thrive arises as a complication of a heterogeneous group of disorders. We describe two female siblings with spastic paraplegia and global developmental delay but also, atypically for the HSPs, poor weight gain classified as failure to thrive. After extensive clinical and biochemical investigations failed to identify the etiology, we used exome sequencing to identify biallelic UNC80 mutations (NM_032504.1:c.[3983‐3_3994delinsA];[2431C>T]. The paternally inherited NM_032504.1:c.3983‐3_3994delinsA is predicted to encode p.Ser1328Argfs*19 and the maternally inherited NM_032504.1:c.2431C>T is predicted to encode p.Arg811*. No UNC80 mRNA was detectable in patient cultured skin fibroblasts, suggesting UNC80 loss of function by nonsense mediated mRNA decay. Further supporting the UNC80 mutations as causative of these siblings’ disorder, biallelic mutations in UNC80 have recently been described among individuals with an overlapping phenotype. This report expands the disease spectrum associated with UNC80 mutations. © 2016 Wiley Periodicals, Inc.