This report describes hydrolethalus syndrome 1 (HLS1); HLS1 exhibits autosomal recessive inheritance. The human gene implicated in this disease is HYLS1, which is a core centriolar protein that may have a role in ciliogenesis. No gene orthologous to HYLS1 has been identified in Drosophila.
Multiple UAS constructs of the human Hsap\HYLS1 gene have been introduced into flies, including wild-type HYLS1 and a gene carrying a mutational lesion implicated in hydrolethalus syndrome. Variant(s) implicated in human disease tested (as transgenic human gene, HYLS1): the D211G variant form has been introduced into flies.
[updated Jul. 2017 by FlyBase; FBrf0222196]
[HYDROLETHALUS SYNDROME 1; HLS1](https://omim.org/entry/236680)
[HYLS1 CENTRIOLAR AND CILIOGENESIS-ASSOCIATED PROTEIN; HYLS1](https://omim.org/entry/610693)
This lethal syndrome was discovered in Finland in the course of studying the Meckel syndrome (see MIM:249000), which is frequent there (Salonen et al., 1981, pubmed:7028327). Like the Meckel syndrome, this disorder is characterized by polydactyly and central nervous system malformation, but unlike that syndrome, it does not show cystic kidney and liver and the CNS derangement is hydrocephalus not encephalocele. The pregnancy is characterized by hydramnios, which is often massive, and by preterm delivery. The ventricles are open to the subarachnoid space so that the hydrocephalus is external. The foramen magnum is keyhole-shaped. The polydactyly is postaxial in the hands and preaxial in the feet. A highly characteristic hallux duplex is seen in almost no other situation. The feet are clubbed. The mandible is always small and the nose poorly formed; the eyes are hypoplastic. About half the affected have a large atrioventricular communis defect of the heart. Stenosis of the airway and abnormal lobation of the lungs are also found. Prenatal diagnosis by ultrasonography is possible. The grandparents of affected persons come from a thinly populated area of eastern Finland. Salonen et al. (1981) described the syndrome in 28 newborns in 18 Finnish families. Polyhydramnios and stillbirth or neonatal death were the rule. [From MIM:236680, 2016.04.12]
Hydrolethalus 1 (HLS1), is caused by homozygous mutation in the HYLS1 gene. [From MIM:236680, 2016.04.12]
In a C. elegans model, the orthologous Hyls1 protein has been shown to interact with Sas4 and is stably incorporated into centrioles as they form via direct interaction with Sas4. In C. elegans, Sas4 is a core centriolar protein that is required for centriole assembly and centrosome function during cell division. Functional characterization of Hyls1 in C. elegans and Xenopus embryo ciliated epithelium revealed that Hyls1 was dispensable for centriole assembly and centrosome function, but that it was required for the formation of cilia. Immunohistochemical analysis showed that C. elegans Hyls1 localized to a discrete structure at the base of cilia. Mutation of a conserved aspartate corresponding to human asp211 had no effect on Hyls1 localization at the base of cilia, but it compromised the ability of Hyls1 to initiate ciliogenesis. These results suggest that HYLS1 is a core centriolar protein that acts in an early step in ciliogenesis, possibly in the prerequisite apical targeting and/or anchoring of centrioles at the plasma membrane (Dammermann et al., 2009, pubmed:19656802). [From MIM:610693, 2016.04.12]
Most Finnish cases of hydrolethalus syndrome 1 are associated with a 1416A-G transition in the HYLS1 gene, resulting in a D211G change in the HYLS1 protein (Mee, et al., 2005, pubmed:15843405). [From MIM:610693, 2016.04.12]
No gene orthologous to human HYLS1 in Drosophila (DIOPT)
