A human case of SLC35A3‐related skeletal dysplasia. Issue 10 (4th August 2017)

• Record Type: Journal Article
• Authors: Edmondson, Andrew C.; Bedoukian, Emma C.; Deardorff, Matthew A.; McDonald‐McGinn, Donna M.; Li, Xueli; He, Miao; Zackai, Elaine H.
• Is Part Of: American journal of medical genetics. Volume 173:Issue 10(2017)
• Page Start: 2758
• Page End: 2762
• Publication Date: 2017-08-04
• Subjects: congenital disorder of glycosylation -- skeletal dysplasia -- vertebral anomaly; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.38374
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : 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.