Skeletal dysplasia

Gene: GNPNAT1

I don't know

one consanguineous family described, 4 affected individuals, all homozygous for p.Glu76Lys. not seen in population dbs.
not a partiuclarly highly conserved residue, prediction software conflicting results. linkage supports. keep as amber.

Created: 30 Jan 2021, 12:30 p.m. | Last Modified: 30 Jan 2021, 12:30 p.m.

Panel Version: 2.80

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
rhizomelic short stature

Publications

• 32591345

I don't know

Comment on list classification: Amber rating as only one family, but some supporting functional data. Additional cases required to validate pathogenicity of GNPNAT1.

Created: 30 Jul 2020, 12:30 p.m. | Last Modified: 30 Jul 2020, 12:30 p.m.

Panel Version: 2.11

PMID: 32591345 (2020) - Four affected sibs from a consanguineous Pakistani family with skeletal dysplasia, characterised by severe short stature, rhizomelic shortening of the limbs, and metacarpal and metatarsal length irregularities in the hands and feet. WGS revealed a homozygous missense variant (c.226G>A; p.Glu76Lys) in GNPNAT1, which segregating with the phenotype.
Gnpnat1 gene knockdown in primary rat chondrocytes decreased cellular proliferation and expression of chondrocyte differentiation markers, indicating the importance of Gnpnat1 for growth plate chondrocyte proliferation and differentiation.
Sources: Literature

Created: 30 Jul 2020, 11:24 a.m. | Last Modified: 30 Jul 2020, 12:29 p.m.

Panel Version: 2.10

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Rhizomelic skeletal dysplasia

Publications

• 32591345