期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 94, 期 5, 页码 734-744出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2014.03.015
关键词
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资金
- NIH National Human Genome Research Institute [1U54HG006493, 1RC2HG005608, 5R000HG004316]
- NIH National Institute of Child Health and Human Development [1R01HD048895, 5K23HD057331]
- Life Sciences Discovery Fund [2065508, 0905001]
- Washington Research Foundation
Gordon syndrome (GS), or distal arthrogyposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechano-sensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher's exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition.
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