In:
Nature Communications, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2016-02-08)
Abstract:
Craniofacial microsomia (CFM) is a rare congenital anomaly that involves immature derivatives from the first and second pharyngeal arches. The genetic pathogenesis of CFM is still unclear. Here we interrogate 0.9 million genetic variants in 939 CFM cases and 2,012 controls from China. After genotyping of an additional 443 cases and 1,669 controls, we identify 8 significantly associated loci with the most significant SNP rs13089920 (logistic regression P =2.15 × 10 −120 ) and 5 suggestive loci. The above 13 associated loci, harboured by candidates of ROBO1 , GATA3 , GBX2 , FGF3 , NRP2 , EDNRB , SHROOM3 , SEMA7A , PLCD3 , KLF12 and EPAS1 , are found to be enriched for genes involved in neural crest cell (NCC) development and vasculogenesis. We then perform whole-genome sequencing on 21 samples from the case cohort, and identify several novel loss-of-function mutations within the associated loci. Our results provide new insights into genetic background of craniofacial microsomia.
Type of Medium:
Online Resource
ISSN:
2041-1723
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2016
detail.hit.zdb_id:
2553671-0
Permalink