Hydrocephalus_Ventriculomegaly

Gene: HYLS1

I don't know

A recurring homozygous missense variant p.Asp211Gly has been identified in at least 64 cases of hydrolethalus syndrome, described as a Finnish founder mutation (PMID: 15843405, PMID: 18648327). Functional studies in human and patient cells have shown mislocalisation of the protein to the nucleus (PMID: 15843405, PMID: 19400947). Functional studies in c. elegans showed that this variant impaired ciliogenesis (PMID: 19656802). Functional studies in drosophila showed that deletion of HYLS1 led to cilia dysfunction (PMID: 32509774). 2 homozygous living siblings (stop-loss, extension variant p.Ter300TyrextTer11) both diagnosed with Joubert syndrome. Patients had molar tooth signs and dysplasia of cerebellar vermis (PMID: 26830932). No other variants have been reported as pathogenic in this gene. Amber rating given only single founder variant reported with a hydrocephalus phenotype with supporting functional data from multiple animal models indicative of ciliopathy.

Created: 6 Aug 2020, 11:47 p.m. | Last Modified: 6 Aug 2020, 11:47 p.m.

Panel Version: 0.21

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hydrolethalus syndrome (MIM#236680)

Publications

• 15843405
• 18648327
• 19400947
• 19656802
• 32509774