Skeletal dysplasia

Gene: SLC13A1

I don't know

The article reports 5 children (two are fraternal twins) presenting with abnormal skeletal findings along with some dysmorphic facial features.
Either homozygous or compound heterozygous variants in SLC13A1 were identified in each child. The compound heterozygous variants were confirmed in trans.
Three missense and two nonsense variants were identified - p.(Gly448Asp), p.(Leu516Pro), and p.(Tyr582His) p.(Arg12*) and NM_022444.4:c.144G>A p.(Trp48*). These variants are present in gnomAD v4.1 and the nonsense variants are too common for AR gene association.

Created: 5 Jan 2025, 10:35 p.m. | Last Modified: 5 Jan 2025, 10:35 p.m.

Panel Version: 0.298

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
sulfation-related bone disorder MONDO:0019688

Publications

• doi: https://doi.org/10.1016/j.gimo.2024.101958

Comment on list classification: Lots of hets and 1 hom, authors claim "predisposing to degenerative bone and joint disease"

Created: 6 Oct 2022, 3:42 a.m. | Last Modified: 6 Oct 2022, 3:42 a.m.

Panel Version: 0.213

Red List (low evidence)

PMID: 36175384- 1 patient with a homozygous nonsense variant in SLC13A1. Patient has enlargements of the joints, and spondylo-epi-metaphyseal radiological abnormalities in early childhood, which improved with age. Also autistic features and hyposulfatemia and hypersulfaturia, and reduced serum cholesterol sulfate. However the variant in this individual (Arg12Ter) has 569 hets and 1 hom in gnomad.

Also this patient was homozygous for CFTR Ala455Gly which is a known pathogenic variant associated with a less severe CF phenotype.
Sources: Literature

Created: 6 Oct 2022, 3:20 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
sulfation-related bone disorder MONDO:0019688, SLC13A1-related

Publications

• 36175384