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PLoS One. 2014 Jul 1;9(7):e101152. doi: 10.1371/journal.pone.0101152. eCollection 2014.

Genome-wide linkage study suggests a susceptibility locus for isolated bilateral microtia on 4p15.32-4p16.2.

Author information

  • 1Beijing Institute of Genomics, Chinese Academy of Sciences and Key Laboratory of Genome Science and Information, Chinese Academy of Sciences, Beijing, P. R. China; Department of Cardiology, Beijing Anzhen Hospital of the Capital University of Medical Sciences, Beijing, P. R. China.
  • 2Department of Ear Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Beijing, P.R. China.
  • 3Beijing Institute of Genomics, Chinese Academy of Sciences and Key Laboratory of Genome Science and Information, Chinese Academy of Sciences, Beijing, P. R. China.

Abstract

Microtia is a congenital deformity where the external ear is underdeveloped. Genetic investigations have identified many susceptibility genes of microtia-related syndromes. However, no causal genes were reported for isolated microtia, the main form of microtia. We conducted a genome-wide linkage analysis on a 5-generation Chinese pedigree with isolated bilateral microtia. We identified a suggestive linkage locus on 4p15.32-4p16.2 with parametric LOD score of 2.70 and nonparametric linkage score (Zmean) of 12.28 (simulated occurrence per genome scan equal to 0.46 and 0.47, respectively). Haplotype reconstruction analysis of the 4p15.32-4p16.2 region further confined the linkage signal to a 10-Mb segment located between rs12505562 and rs12649803 (9.65-30.24 cM; 5.54-15.58 Mb). Various human organ developmental genes reside in this 10-Mb susceptibility region, such as EVC, EVC2, SLC2A9, NKX3-2, and HMX1. The coding regions of three genes, EVC known for cartilage development and NKX3-2, HMX1 involved in microtia, were selected for sequencing with 5 individuals from the pedigree. Of the 38 identified sequence variants, none segregates along with the disease phenotype. Other genes or DNA sequences of the 10-Mb region warrant for further investigation. In conclusion, we report a susceptibility locus of isolated microtia, and this finding will encourage future studies on the genetic basis of ear deformity.

PMID:
24983964
[PubMed - in process]
PMCID:
PMC4077761
Free PMC Article
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