title: Phenotypic evolution of UNC80 loss of function.
abstract: 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.
authors: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, National Institutes of Health, Bethesda, Maryland.
authors: Elise
authors: E
authors: Valkanas
authors: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, National Institutes of Health, Bethesda, Maryland.
authors: Katherine
authors: K
authors: Schaffer
authors: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors: Christopher
authors: C
authors: Dunham
authors: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, National Institutes of Health, Bethesda, Maryland.
authors: Valerie
authors: V
authors: Maduro
authors: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.|Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors: Christèle
authors: C
authors: du Souich
authors: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.|Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors: Rosemarie
authors: R
authors: Rupps
authors: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, National Institutes of Health, Bethesda, Maryland.
authors: David R
authors: DR
authors: Adams
authors: Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.|Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors: Alireza
authors: A
authors: Baradaran-Heravi
authors: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, National Institutes of Health, Bethesda, Maryland.
authors: Elise
authors: E
authors: Flynn
authors: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, National Institutes of Health, Bethesda, Maryland.
authors: May C
authors: MC
authors: Malicdan
authors: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, National Institutes of Health, Bethesda, Maryland.|NHGRI, National Institutes of Health, Bethesda, Maryland.
authors: William A
authors: WA
authors: Gahl
authors: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, National Institutes of Health, Bethesda, Maryland.
authors: Camilo
authors: C
authors: Toro
authors: NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, National Institutes of Health, Bethesda, Maryland.|Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.|Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors: Cornelius F
authors: CF
authors: Boerkoel
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D005183:Failure to Thrive / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D010264:Paraplegia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D020871:RNA Stability / Q000235:genetics; D035781:Siblings
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C544680:Unc80 protein, human
keywords: emaciation; failure to thrive; growth restriction; intellectual disability; seizures