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Hydrolethalus syndrome 1 (HLS1)

Genes

  • HYLS1 - centriolar and ciliogenesis associated (HYLS1)

Summary

Hydrolethalus syndrome 1 is a severe complex malformation syndrome, which leads to death of the fetus in most cases in utero, or immediately after the birth. The causative gene is HYLS1, located at chromosome 11q24. It has been suggested that HYLS1 is a transcriptional regulator that shuffles between the cytoplasm and the nucleus. Other experiments have shown HYLS1 to be a conserved centriolar protein that is stably incorporated into centrioles and to have an essential role in cilia formation. In Hydrolethalus syndrome, a single amino acid substitution in protein encoded by HYLS1 impairs its function. The characteristic malformations in HYLS1 are external asymmetric hydrocephalus, a keyhole-shaped foramen magnum and polydactyly in all extremities. Other common findings are poorly developed mandible, small, often bifid nose and hypoplastic eyes. Atrioventricular communis defect of the heart is frequently found as well as abnormal lobation of the lungs. Careful clinical examination provides the diagnosis of the hydrolethalus syndrome distinct from Meckel syndrome. Prenatal diagnosis by ultrasound can often be established already at 12th week of gestation. A gene test is available.

Links

UMLS Concepts by OMIM 236680

C1856016 / HYDROLETHALUS SYNDROME 1 / HLS1
Other concept sources:
  • MTH NOCODE - HYDROLETHALUS SYNDROME 1
  • MSH C565504 - Hydrolethalus Syndrome 1

Selected publications

  • Mee L, Honkala H, Kopra O, Vesa J, Finnilä S, Visapää I, Sang TK, Jackson GR, Salonen R, Kestilä M, Peltonen L. Hydrolethalus syndrome is caused by a missense mutation in a novel gene HYLS1. Hum Mol Genet. 2005 Jun 1;14(11):1475-88 (Pubmed)
  • Honkala H, Lahtela J, Fox H, Gentile M, Pakkasjärvi N, Salonen R, Wartiovaara K, Jauhiainen M, Kestilä M. Unraveling the disease pathogenesis behind lethal hydrolethalus syndrome revealed multiple changes in molecular and cellular level. Pathogenetics. 2009 Apr 28;2(1):2 (Pubmed)
  • Dammermann A, Pemble H, Mitchell BJ, McLeod I, Yates JR 3rd, Kintner C, Desai AB, Oegema K: The hydrolethalus syndrome protein HYLS-1 links core centriole structure to cilia formation. Genes Dev. 2009 Sep 1;23(17):2046-59. (Pubmed)