%0 Journal Article
%T Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy
%A Ali Al£¿Asmari
%A Ayman£¿W. El-Hattab
%A Baylor-Hopkins Center for Mendelian Genomics
%A Charles£¿A. LeDuc
%A Davut Pehlivan
%A Donna Muzny
%A Ender Karaca
%A Eric Boerwinkle
%A Gozde Yesil
%A James£¿R. Lupski
%A Jill£¿A. Rosenfeld
%A Jill£¿V. Hunter
%A John£¿W. Belmont
%A Mohammad£¿K. Eldomery
%A Mohammed£¿A. Saleh
%A Richard£¿A. Gibbs
%A Shalini£¿N. Jhangiani
%A Wendy£¿K. Chung
%A Wu-Lin Charng
%A Yaping Yang
%A Yavuz Bayram
%A Zeynep Coban-Akdemir
%J Archive of "American Journal of Human Genetics".
%D 2016
%R 10.1016/j.ajhg.2016.01.011
%X The paradigm of a single gene associated with one specific phenotype and mode of inheritance has been repeatedly challenged. Genotype-phenotype correlations can often be traced to different mutation types, localization of the variants in distinct protein domains, or the trigger of or escape from nonsense-mediated decay. Using whole-exome sequencing, we identified homozygous variants in EMC1 that segregated with a phenotype of developmental delay, hypotonia, scoliosis, and cerebellar atrophy in three families. In addition, a de novo heterozygous EMC1 variant was seen in an individual with a similar clinical and MRI imaging phenotype. EMC1 encodes a member of the endoplasmic reticulum (ER)-membrane protein complex (EMC), an evolutionarily conserved complex that has been proposed to have multiple roles in ER-associated degradation, ER-mitochondria tethering, and proper assembly of multi-pass transmembrane proteins. Perturbations of protein folding and organelle crosstalk have been implicated in neurodegenerative processes including cerebellar atrophy. We propose EMC1 as a gene in which either biallelic or monoallelic variants might lead to a syndrome including intellectual disability and preferential degeneration of the cerebellum
%K Whole-exome sequencing
%K EMC1
%K endoplasmic reticulum (ER)-membrane complex
%K mitochondrial membrane
%K inter-organellar communication
%K intracellular transport
%K neurodegeneration
%K cerebellar atrophy
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800043/