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A human case of SLC35A3 ‐related skeletal dysplasia
Author(s) -
Edmondson Andrew C.,
Bedoukian Emma C.,
Deardorff Matthew A.,
McDonaldMcGinn Donna M.,
Li Xueli,
He Miao,
Zackai Elaine H.
Publication year - 2017
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.38374
Subject(s) - camptodactyly , medicine , missense mutation , exome sequencing , brachydactyly , dysplasia , anatomy , pathology , genetics , phenotype , short stature , biology , pediatrics , gene
Researchers have identified a subset of Holstein having a range of skeletal deformities, including vertebral anomalies, referred to as complex vertebral malformation due to mutations in the SLC35A3 gene. Here, we report the first case in humans of SLC35A3 ‐related vertebral anomalies. Our patient had prenatally diagnosed anomalous vertebrae, including butterfly, and hemivertebrae throughout the spine, as well as cleft palate, micrognathia, patent foramen ovale, patent ductus arteriosus, posterior embryotoxon, short limbs, camptodactyly, talipes valgus, rocker bottom feet, and facial dysmorphism including proptosis, nevus flammeus, and a cupped left ear. Clinical exome sequencing revealed a novel missense homozygous mutation in SLC35A3 . Follow‐up biochemical analysis confirmed abnormal protein glycosylation, consistent with a defective Golgi UDP‐GlcNAc transporter, validating the mutations. Congenital disorders of glycosylation, including SLC35A3‐CDG, can present as a wide phenotypic spectrum, including skeletal dysplasia. Previously reported patients with SLC35A3‐CDG have been described with syndromic autism, epilepsy, and arthrogryposis.