Identification of rare PTCH1 nonsense variant causing orofacial cleft in a Chinese family and an up-to-date genotype-phenotype analysis

Wenjie Zhong; Huaxiang Zhao; Wenbin Huang; Mengqi Zhang; Qian Zhang; Yue Zhang; Chong Chen; Zulihumaer Nueraihemaiti; Dilifeire Tuerhong; Huizhe Huang; Gulibaha Maimaitili; Feng Chen; Jiuxiang Lin

doi:10.1016/j.gendis.2019.12.010

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Identification of rare PTCH1 nonsense variant causing orofacial cleft in a Chinese family and an up-to-date genotype-phenotype analysis

更新时间：2022-06-24

- Identification of rare PTCH1 nonsense variant causing orofacial cleft in a Chinese family and an up-to-date genotype-phenotype analysis
- Genes & Diseases Vol. 8, Issue 5, (2021)
- 作者机构：
  
  1. Department of Orthodontics, Peking University School and Hospital of Stomatology,Beijing,PR China,100081
  2. Central Laboratory, Peking University School and Hospital of Stomatology,Beijing,PR China,100081
  3. Department of Stomatology, The Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi,PR China,830000
  4. Xinjiang Medical University,Urumqi,PR China,830000
  5. Chongqing Medical University,Chongqing,PR China,400016
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2019.12.010
  CLC：
- Published：2021，
  
  Published Online：1 September 2021，
扫描看全文
Wenjie Zhong, Huaxiang Zhao, Wenbin Huang, et al. Identification of rare PTCH1 nonsense variant causing orofacial cleft in a Chinese family and an up-to-date genotype-phenotype analysis. [J]. Genes & Diseases 8(5).(2021)
DOI：

Wenjie Zhong, Huaxiang Zhao, Wenbin Huang, et al. Identification of rare PTCH1 nonsense variant causing orofacial cleft in a Chinese family and an up-to-date genotype-phenotype analysis. [J]. Genes & Diseases 8(5).(2021) DOI： 10.1016/j.gendis.2019.12.010.

摘要

Abstract

The Patched 1 (

PTCH1

) gene encodes a membrane receptor involved in the Hedgehog (Hh) signaling pathway

an abnormal state of which may result in congenital defects or human tumors. In this study

we conducted whole-exome sequencing on a three-generation Chinese family characterized with variable penetrance of orofacial clefts. A rare heterozygous variant in the

PTCH1

gene (c.2833C

T p.R945X) was identified as a disease-associated mutation. Structural modeling revealed a truncation starting from the middle of the second extracellular domain of PTCH1 protein. This may damage its ligand recognition and sterol transportation abilities

thereby affecting the Hh signaling pathway. Biochemical assays indicated that the R945X protein had reduced stability compared to the wild-type

in vitro

. In addition

we reviewed the locations and mutation types of

PTCH1

variants in individuals with clefting phenotypes

and analyzed the associations between clefts and locations or types of variants within

PTCH1

. Our findings provide further evidence that

PTCH1

variants result in orofacial clefts

and contributed to genetic counseling and clinical surveillance in this family.

关键词

Keywords

Cleft lip with or without palateClinical geneticsGenotype-phenotype analysisPTCH1Whole-exome sequencing

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Related Institution

Department of Nephrology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics

Department of Nephrology, Chengdu Women and Children Central Hospital

Department of Nephrology, Sheen Children's Hospital

Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University

Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology

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