| First Author | Shen Q | Year | 2018 |
| Journal | Gene | Volume | 658 |
| Pages | 96-104 | PubMed ID | 29477871 |
| Mgi Jnum | J:261959 | Mgi Id | MGI:6159178 |
| Doi | 10.1016/j.gene.2018.02.054 | Citation | Shen Q, et al. (2018) Identification of two novel PCDHA9 mutations associated with Hirschsprung's disease. Gene 658:96-104 |
| abstractText | Hirschsprung's disease (HSCR) is a complex disorder with multiple pathogenic gene mutations. Protocadherin alpha 9 (PCDHA9) was identified as a potential candidate gene for HSCR by whole-exome sequencing in a Chinese family. Sanger sequencing in 298 HSCR cases revealed two sporadic Chinese patients with a novel missence PCDHAlpha9 mutation (NM_031857; c.1280C>T[p.Ala427Val]) and one sporadic Chinese patient with another novel missence PCDHAlpha9 mutation (c.1425C>G[p.Phe475Leu]).The silico predictions and 3D modeling suggest the deleterious effect of identified mutations on protein function. Immunohistochemistry analysis showed PCDHAlpha9 was predominantly expressed in the myenteric plexus of human colon tissues. For mouse embryos, PCDHAlpha9 was expressed in the stomach but rarely seen in the intestine during E10.5-12.5, then obviously expressed in the intestinal mucosa at E13.5 and extensively expressed in intestinal muscularis and mucosa at E14.5. Moreover, the down-regulation of PCDHAlpha9 in the SH-SY5Y cell line promoted the proliferation and migration rate but inhibited the apoptotic rate. In summary, PCDHAlpha9 is potentially related to HSCR and the clustered protocadherins (Pcdhs) may involve in the enteric nervous system (ENS) ontogeny. |
