Genes in panel

Inborn errors of metabolism

Gene: CSGALNACT1

Amber List (moderate evidence)

CSGALNACT1 (chondroitin sulfate N-acetylgalactosaminyltransferase 1)
EnsemblGeneIds (GRCh38): ENSG00000147408
EnsemblGeneIds (GRCh37): ENSG00000147408
OMIM: 616615, Gene2Phenotype
CSGALNACT1 is in 3 panels

2 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoting from grey to amber, but with recommendation for green rating following GMS review as there are now 4 cases reported of biallelic variants in this gene in patients with mild skeletal dysplasia thought to result from disturbance of glycosaminoglycan synthesis.
Created: 13 Jan 2021, 3:42 p.m. | Last Modified: 13 Jan 2021, 3:42 p.m.
Panel Version: 2.23
As Zornitza Stark reports, 4 cases have been published

PMID: 27599773 Vodopiutz et al 2017 - infant with prenatal-onset disproportionate short stature, joint laxity, and radiographic findings typical for Desbuquois dysplasia was found to be compound-heterozygous for a large (55kb) intragenic deletion, and a p.Pro384Arg missense mutation in CSGALNACT1, each inherited from a parent.

PMID: 31325655 Meyer et al 2019 - 12 year old boy with a mild skeletal dysplasia, hypermobility of joints and axial malalignment of lower limbs and feet. He has consanguineous parents from Turkey. Exome sequencing revealed a biallelic frameshift mutation (NM_018371.4:c.372del, p.(His125Thrfs*9)) in CSGALNACT1. Csgalnact1−/− mice have reduced body length with shortened long bones.

PMID: 31705726 Mizumoto et al 2020 - two unrelated cases presenting with short stature with advanced bone age, facial dysmorphism, and mild language delay. P2 (male) was found by WES to be compound‐heterozygous for a missense variant (c.1294G>T (p.Asp432Tyr)) and an intragenic deletion of 84kb that removes exon 4. P3 (female) was found by WES to be homozygous for a missense variant in CSGALNACT1 (c.791A>G (p.Asn264Ser) due to complete paternal isodisomy for chromosome 8, which harbors CSGALNACT1. The healthy father was heterozygous for this variant and the healthy mother was WT CSGALNACT1. P3 was also homozygous for a VPS13B variant causing a frameshift due to paternal isodisomy 8. Recessive variants in this gene are associated with Cohen syndrome but her clinical features do not overlap with this syndrome and the variant only impacts a short alternate isoform. Functional studies with patient fibroblasts showed that biallelic loss‐of‐function mutations in CSGALNACT1 disturb glycosaminoglycan synthesis.
Created: 13 Jan 2021, 3:39 p.m. | Last Modified: 13 Jan 2021, 3:39 p.m.
Panel Version: 2.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Skeletal dysplasia, mild, with joint laxity and advanced bone age OMIM:618870; skeletal dysplasia, mild, with joint laxity and advanced bone age MONDO:0030029

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Four unrelated families reported. CSGALNACT1 is predicted to transfer GalNAc to both the tetrasaccharide linker and to growing CS chains in proteoglycans.
Sources: Expert list
Created: 22 Jul 2020, 8:44 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation; skeletal dysplasia

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert list
Phenotypes
  • Congenital disorder of glycosylation
  • Skeletal dysplasia, mild, with joint laxity and advanced bone age OMIM:618870
  • skeletal dysplasia, mild, with joint laxity and advanced bone age MONDO:0030029
Tags
Q2_21_rating
OMIM
616615
Clinvar variants
Variants in CSGALNACT1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

5 Aug 2021, Gel status: 2

Removed Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review was removed from gene: CSGALNACT1. Tag Q2_21_rating tag was added to gene: CSGALNACT1.

5 Aug 2021, Gel status: 2

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Arina Puzriakova (Genomics England Curator)

gene: CSGALNACT1 was added gene: CSGALNACT1 was added to Inborn errors of metabolism. Sources: Expert list,Expert Review Amber for-review tags were added to gene: CSGALNACT1. Mode of inheritance for gene: CSGALNACT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CSGALNACT1 were set to 31705726; 31325655; 31705726 Phenotypes for gene: CSGALNACT1 were set to Congenital disorder of glycosylation; Skeletal dysplasia, mild, with joint laxity and advanced bone age OMIM:618870; skeletal dysplasia, mild, with joint laxity and advanced bone age MONDO:0030029