Mutational analysis of GSC, HOXA2 and PRKRA in 106 Chinese patients with microtia

Int J Pediatr Otorhinolaryngol. 2017 Feb:93:78-82. doi: 10.1016/j.ijporl.2016.12.026. Epub 2016 Dec 26.

Abstract

Objective: Microtia is defined as a developmental malformation characterized by a small, abnormal shaped auricle, with atresia or stenosis of the auditory canal. Genes responsible for nonsyndromic microtia have remained elusive. We therefore report a mutational analysis of GSC, HOXA2 and PRKRA in 106 congenital microtia patients without any combined malformation to explore the relationship between GSC, HOXA2, PRKRA and nonsyndromic microtia.

Methods: A total of 106 patients with a clinical diagnosis of congenital microtia and a control group (100 unaffected controls) were recruited through the Eye and ENT Hospital of Fudan University in China. Genomic DNA was extracted following a standard protocol. DNA sequencing analysis was performed in all exons and the exon-intron borders of GSC, HOXA2 and PRKRA.

Results: We identified 5 genomic variants in GSC, HOXA2 and PRKRA. As to the GSC, we obtained a reported variant g.994C > T in exon 2, which resulted in no change of protein. Our results revealed that g.994C > T was also detected in 10 control cases. We also detected 2 novel variants, g.90G > A and g.114A > C, in the 5'UTR of HOXA2. No class 5 or 4 genomic variant of PRKRA was identified in our microtia patients. Additionally, two previously reported SNVs in GSC and PRKRA were also presented.

Conclusions: We suggest that g.994C > T is a new SNV, which is different from the previous report. Further study is needed to prove the function of 2 novel variants in the 5'UTR of HOXA2, and to explore the possible mechanism of these variants in the occurrence of microtia.

Keywords: Chinese; GSC gene; HOXA2 gene; Microtia; PRKRA gene.

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Child
  • Child, Preschool
  • China
  • Congenital Microtia / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Markers
  • Goosecoid Protein / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Infant
  • Male
  • Mutation*
  • RNA-Binding Proteins / genetics*

Substances

  • GSC protein, human
  • Genetic Markers
  • Goosecoid Protein
  • HOXA2 protein, human
  • Homeodomain Proteins
  • PRKRA protein, human
  • RNA-Binding Proteins