title: Mutational analysis of GSC, HOXA2 and PRKRA in 106 Chinese patients with microtia.
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.
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Zhengzhou University, Henan, China. Electronic address: haoshaojuan666@163.com.
authors.forename: Shaojuan
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, China.
authors.forename: Chenlong
authors.initials: C
authors.lastname: Li
authors.affiliation: Birth Defect & Pathology Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Birth Defect & Pathology Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Birth Defect & Pathology Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China; Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, China. Electronic address: ty.zhang2006@aliyun.com.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China; D065817:Congenital Microtia / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers; D051956:Goosecoid Protein / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: C497992:GSC protein, human; D005819:Genetic Markers; D051956:Goosecoid Protein; C520321:HOXA2 protein, human; D018398:Homeodomain Proteins; C104647:PRKRA protein, human; D016601:RNA-Binding Proteins
keywords: Chinese; GSC gene; HOXA2 gene; Microtia; PRKRA gene