Yunis-Varón syndrome gene identification links this skeletal dysplasia with neurological involvement to phosphoinositide metabolism

Posted by & filed under Part 16: LYSOSOMAL DISORDERS, Part 22: CONNECTIVE TISSUE, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

Yunis-Varón syndrome is a skeletal dyplasia with features of cleidocranial dysplasia, with digital hypoplasia and severe neurological involvement (http://omim.org/entry/216340). Through exome sequencing, we identified three families with mutations of FIG4, encoding a phosphoinositide phosphatase. This enzyme had previously been implicated in Charcot-Marie-Tooth type 4J (CMT-4J). While CMT-4J is usually caused by a combination of a truncating mutation and a missense mutation leaving residual activity of the enzyme, we show that the mutations causing Yunis-Varón syndrome essentially abolish the activity of FIG4. A mouse model of FIG4 deficiency reproduces some, but not all skeletal features of the disease.

Campeau PM, Lenk GM, Lu JT, Bae Y, Burrage L, Turnpenny P, Román Corona-Rivera J, Morandi L, Mora M, Reutter H, Vulto-van Silfhout AT, Faivre L, Haan E, Gibbs RA, Meisler MH, Lee BH.
Yunis-Varón syndrome is caused by mutations in FIG4, encoding a phosphoinositide phosphatase.
Am J Hum Genet. 2013 May 2;92(5):781-91. doi: 10.1016/j.ajhg.2013.03.020. Epub 2013 Apr 25. PubMed PMID: 23623387; PubMed Central PMCID: PMC3644641.

Posted by Philippe Campeau, MD
Assistant Professor, Department of Molecular and Human Genetics, Baylor College of Medicine

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