A B3GALT6 variant in patient originally described as Al-Gazali syndrome and implicating the endoplasmic reticulum quality control in the mechanism of some β3GalT6-pathy mutations

A. Ben-Mahmoud, S. Ben-Salem, M. Al-Sorkhy, A. John, B. R. Ali, L. Al-Gazali

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Al-Gazali syndrome encompasses several clinical features including prenatal growth retardation, large joints contractures with camptodactyly, bilateral talipes equinovarus, small mouth, anterior segment anomalies of the eyes, and early lethality. Recently, a baby with features very similar to Al-Gazali syndrome was found to have compound heterozygous variants in B3GALT6. This gene encodes Beta-1,3-galactosyltransferase 6 (β3GalT6), an essential component of the glycosaminoglycan synthesis pathway. Pathogenic variants in B3GALT6 have also been shown to cause Ehlers-Danlos syndrome spondylodysplastic type (spEDS-B3GALT6) and spondyloepimetaphyseal dysplasia with joint laxity type I (SEMD-JL1). In 2017, a new international classification of EDS included these 2 conditions together with the child reported to have features similar to Al-Gazali syndrome under spondylodysplastic EDS (spEDS). We report a disease-causing variant c.618C > G, p.(Cys206Trp) in 1 patient originally described as Al-Gazali syndrome and reported in 1999. We evaluated the involvement of the endoplasmic reticulum-associated protein degradation, in the pathogenesis of 13 B3GALT6 variants. Retention in endoplasmic reticulum was evident in 6 of them while the c.618C > G, p.(Cys206Trp) and the other 6 variants trafficked normally. Our findings confirm the involvement of B3GALT6 in the pathogenesis of Al-Gazali syndrome and suggest that Al-Gazali syndrome represents the severe end of the spectrum of the phenotypes caused by pathogenic variants in this gene.

Original languageEnglish
Pages (from-to)1148-1158
Number of pages11
JournalClinical Genetics
Volume93
Issue number6
DOIs
Publication statusPublished - Jun 2018

Keywords

  • Al-Gazali syndrome
  • B3GALT6 variant
  • ER quality control
  • defective GAGs synthesis
  • β3GalT6-pathy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'A B3GALT6 variant in patient originally described as Al-Gazali syndrome and implicating the endoplasmic reticulum quality control in the mechanism of some β3GalT6-pathy mutations'. Together they form a unique fingerprint.

Cite this