Skeletal dysplasia

Gene: ALG9

Green List (high evidence)

Bi-allelic variants and CDG: At least 7 unrelated families reported. Clinical features include failure to thrive, dysmorphic features, seizures, hepatic and/or renal cysts; three patients died in utero from a lethal skeletal dysplasia. The severe end of the spectrum is referred to as Gillessen-Kaesbach-Nishimura syndrome and is characterised by skeletal dysplasia, dysmorphic facial features, and variable visceral abnormalities, including polycystic kidneys, diaphragmatic hernia, lung hypoplasia, and congenital heart defects. It may be lethal in utero or early in life.

Mono-allelic variants and polycystic kidney disease: Two individuals with mono-allelic variants reported with polycystic kidney disease, and ALG9 LOF variants over-represented in a population-based cohort, additional individual reported as part of a large cohort. However, penetrance and expressivity seem variable, and also it is unclear whether parents of children affected by the AR CDG have renal cysts. MODERATE evidence for gene-disease association.

Created: 25 Nov 2020, 9:34 a.m. | Last Modified: 25 Nov 2020, 9:34 a.m.

Panel Version: 0.5452

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation, type Il, MIM#608776; Gillessen-Kaesbach-Nishimura syndrome, MIM# 263210; Polycystic kidney disease

Publications

• 28932688
• 25966638
• 26453364
• 30676690