Callosome

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 on this panel as only the hydrolethalus phenotype has been reported in association with absent corpus callosum in the setting of very severe brain malformation.

Created: 7 Aug 2020, 12:06 a.m. | Last Modified: 7 Aug 2020, 12:06 a.m.

Panel Version: 0.179

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hydrolethalus syndrome (MIM#236680)

Publications

• 15843405
• 18648327
• 19400947
• 19656802
• 32509774
• 26830932