Mutations inPOMT1 are found in a minority of patients with Walker-Warburg syndrome

Autor: Wafaa Eyaid, Greg Enns, Adria Bodell, G. Shashidhar Pai, Leela Job, William B. Dobyns, Christine K. Lee, Christopher A. Walsh, Bernard S. Chang, Lieven Lagae, Sophie Currier, Lihadh Al-Gazali
Rok vydání: 2005
Předmět:
Zdroj: American Journal of Medical Genetics Part A. :53-57
ISSN: 1552-4833
1552-4825
Popis: Department of Human Genetics, Neurology and Pediatrics, University of Chicago, Chicago, IllinoisWalker–Warburg syndrome (WWS) is an autoso-mal recessive disorder of infancy characterizedby hydrocephalus, agyria, retinal dysplasia, con-genital muscular dystrophy, and over migrationof neurons through a disrupted pial surfaceresulting in leptomeningeal heterotopia. Alth-ough previous work identified mutations in theo-mannosyl transferase, POMT1, in 6 out of 30WWS families [Beltran-Valero de Bernabe et al.,2002], the incidence of POMT1 mutations in WWSis not known. We sequenced the entire codingregion of POMT1 in 30 consecutive, unselectedpatients with classic WWS. Two novel heterozy-gous mutations were found in two patients fromnon-consanguineous parents, whereas 28 otherpatientsfailedtoshowanyPOMT1mutations.Onepatient was found to be heterozygous for atransition, g.1233T>A, which predicts p.Y352X.A second patient was found also to be heterozy-gous for a transition g.1790C>G, which predictsp.S537R. As an additional determination of thefrequency of the POMT1 mutations in WWS, wetested for linkage of WWS to POMT1 in sixconsanguineous families. All six demonstratedheterozygosity and negative LOD scores at thePOMT1 locus. From these data we show thatPOMT1 is an uncommon cause of WWS, the inci-dence of coding region mutations in this popula-tion of WWS being less than 7%. We conclude thatwhile the incidence of POMT1 mutations in WWScan be as high as 20% as reported by Beltran-ValerodeBernabeetal.[2002]anditcanbeaslowas 7%, as reported here.
Databáze: OpenAIRE
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