[PDF][PDF] Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5
MJ McMillin, AE Beck, JX Chong, KM Shively… - The American Journal of …, 2014 - cell.com
MJ McMillin, AE Beck, JX Chong, KM Shively, KJ Buckingham, HIS Gildersleeve, MI Aracena…
The American Journal of Human Genetics, 2014•cell.comGordon syndrome (GS), or distal arthrogryposis 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
mechanosensitive 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 …
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
mechanosensitive 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 …
Gordon syndrome (GS), or distal arthrogryposis 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 mechanosensitive 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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