A 3.06-Mb interstitial deletion on 12p11.22-12.1 caused brachydactyly type E combined with pectus carinatum

作     者：Jia Huang Hong-Yan Liu Rong-Rong Wang Hai Xiao Dong Wu Tao Li Ying-Hai Jiang Xue Zhang Huang Jia;Liu Hong-Yan;Wang Rong-Rong;Xiao Hai;Wu Dong;Li Tao;Jiang Ying-Hai;Zhang Xue

作者机构：The Research Center for Medical GenomicsKey Laboratory of Medical Cell BiologyChinese Ministry of EducationCollege of Basic Medical ScienceChina Medical UniversityShenyangLiaoning 110122China Institute of Medical GeneticsHenan Provincial People's HospitalPeople's Hospital of Zhengzhou UniversitySchool of Clinical MedicineHenan UniversityZhengzhouHenan 450003China McKusick-Zhang Center for Genetic MedicineState Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2019年第132卷第14期

页      面：1681-1688页

核心收录：

学科分类：1002[医学-临床医学] 10[医学] 

基　　金：supported by grants from the National Key Research and Development Program of China the CAMS Innovation Fund for Medical Sciences (CIFMS) Medical Science and Technology Key Projects of Henan Province Technology Key Projects of Henan Province Health Bureau 

主　　题：Brachydactyly type E Parathyroid-hormone-like hormone Pectus carinatum Short stature Copy number variation 

摘      要：Background:Brachydactyly,a developmental disorder,refers to shortening of hands/feet due to small or missing metacarpals/ metatarsals and/or phalanges.Isolated brachydactyly type E (BDE),characterized by shortened metacarpals and/or metatarsals,consists in a small proportion of patients with Homeobox D13 (HOXD13) or parathyroid-hormone-like hormone (PTHLH) mutations.BDE is often accompanied by other anomalies that are parts of many congenital syndromes.In this study,we investigated a Chinese family presented with BDE combined with pectus carinatum and short stature.Methods:A four-generation Chinese family was recruited in June 2016.After informed consent was obtained,venous blood was collected,and genomic DNA was extracted by standard procedures.Whole-exome sequencing was performed to screen pathogenic mutation,array comparative genomic hybridization (Array-CGH) analysis was used to analyze copy number variations,and quantitative real-time polymerase chain reaction (PCR),stride over breakpoint PCR (gap-PCR),and Sanger sequencing were performed to confirm the candidate variation.Results:A 3.06-Mb deletion (chr12:25473650-28536747) was identified and segregated with the phenotype in this family.The deletion region encompasses 23 annotated genes,one of which is PTHLH which has been reported to be causative to the BDE.PTHLH is an important regulator of endochondral bone development.The affected individuals showed bilateral,severe,and generalized brachydactyly with short stature,pectus carinatum,and prematurely fusion of epiphyses.The feature of pectus carinatum has not been described in the PTHLH-related BDE patients previously.Conclusions:The haploinsufficiency of PTHLH might be responsible for the disease in this family.This study has expanded the knowledge on the phenotypic presentation of PTHLH variation.