title: Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT, encoding an EGF domain-specific O-GlcNAc transferase.
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.
authors.affiliation: The Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev (NIBN) and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel.
authors.forename: Idan
authors.initials: I
authors.lastname: Cohen
authors.affiliation: Department of Plastic and Reconstructive Surgery, Soroka Medical Center, Beer-Sheva, Israel.
authors.forename: Eldad
authors.initials: E
authors.lastname: Silberstein
authors.affiliation: The Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev (NIBN) and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Perez
authors.affiliation: Division of Pediatrics, Soroka Medical Center, Beer-Sheva, Israel.
authors.forename: Daniella
authors.initials: D
authors.lastname: Landau
authors.affiliation: The Genetics Institute, Soroka Medical Center, Beer-Sheva, Israel.
authors.forename: Khalil
authors.initials: K
authors.lastname: Elbedour
authors.affiliation: 1] The Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev (NIBN) and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel [2] The Genetics Institute, Soroka Medical Center, Beer-Sheva, Israel.
authors.forename: Yshaia
authors.initials: Y
authors.lastname: Langer
authors.affiliation: The Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev (NIBN) and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel.
authors.forename: Rotem
authors.initials: R
authors.lastname: Kadir
authors.affiliation: The Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev (NIBN) and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Volodarsky
authors.affiliation: The Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev (NIBN) and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Sivan
authors.affiliation: The Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev (NIBN) and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel.
authors.forename: Ginat
authors.initials: G
authors.lastname: Narkis
authors.affiliation: 1] The Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev (NIBN) and Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel [2] The Genetics Institute, Soroka Medical Center, Beer-Sheva, Israel.
authors.forename: Ohad S
authors.initials: OS
authors.lastname: Birk
mesh_terms: D000293:Adolescent; D017398:Alternative Splicing; D002648:Child; D002675:Child, Preschool; D004476:Ectodermal Dysplasia / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017880:Limb Deformities, Congenital / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D008297:Male; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D012536:Scalp Dermatoses / Q000151:congenital* / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics
chemical_list: D004815:Epidermal Growth Factor; D017351:N-Acetylglucosaminyltransferases