Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase

Cohen, I; Silberstein, E; Perez, Y; Landau, D; Elbedour, K; Langer, Y; Kadir, R; Volodarsky, M; Sivan, S; Narkis, G; Birk, OS

HERO ID

3539481

Reference Type

Journal Article

Year

2014

Language

English

PMID

23860037

HERO ID 3539481
In Press No
Year 2014
Title Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase
Authors Cohen, I; Silberstein, E; Perez, Y; Landau, D; Elbedour, K; Langer, Y; Kadir, R; Volodarsky, M; Sivan, S; Narkis, G; Birk, OS
Journal European Journal of Human Genetics
Volume 22
Issue 3
Page Numbers 374-378
Abstract Autosomal recessive Adams-Oliver syndrome was diagnosed in three remotely related Bedouin consanguineous families. Genome-wide linkage analysis ruled out association with known Adams-Oliver syndrome genes, identifying a single-homozygosity ∼1.8-Mb novel locus common to affected individuals (LOD score 3.37). Whole-exome sequencing followed by Sanger sequencing identified only a single mutation within this locus, shared by all affected individuals and found in patients from five additional apparently unrelated Bedouin families: a 1-bp deletion mutation in a predicted alternative splice variant of EOGT, leading to a putative truncated protein. RT-PCR demonstrated that the EOGT-predicted alternative splice variant is ubiquitously expressed. EOGT encodes EGF-domain-specific O-linked N-acetylglucosamine transferase, responsible for extracellular O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and is essential for epithelial cell-matrix interactions. F-actin staining in diseased fibroblasts showed apparently intact cell cytoskeleton and morphology, suggesting the EOGT mutation acts not through perturbation of cytoskeleton but through other mechanisms yet to be elucidated.
Doi 10.1038/ejhg.2013.159
Pmid 23860037
Wosid WOS:000331393700017
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English