Biomaterial Database

[ZRS mutations in two Chinese Han families featuring triphalangeal thumbs and preaxial polydactyly]. 2016

Ximeng Zhao, and Wei Yang, and Miao Sun, and Xue Zhang

Department of Medical Genetics, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Science Peking Union Medical College School of Basic Medical Science, Beijing 100005, China. votivealice@aliyun.com; xuezhang@pumc.edu.cn.

OBJECTIVE To identify the causative mutations in two Chinese Han families featuring triphalangeal thumbs (TPT) and preaxial polydactyly (PPD). METHODS Blood samples were collected from 9 members (2 affected) from family 1 and 14 members (7 affected) from family 2. After genomic DNA was extracted, the ZPA regulatory sequence (ZRS) region was analyzed with real-time quantitative PCR (qPCR) and Sanger sequencing. For family 1, haplotypes compassing the ZRS were also analyzed with short tandem repeats (STR) and single nucleotide changes. RESULTS No copy number mutation around the ZRS region was found in both families. Two heterogeneous mutations in the ZRS (406A>G and 105C>G) were found to co-segregate with the TPT/PPD malformation in family 1 and 2, respectively. Neither mutation was detected in 200 healthy individuals. Haplotype analysis and Sanger sequencing of family 1 indicated that the first TPT/PPD patient in the family was both germline and somatic mosaic for the 406A>G mutation. CONCLUSIONS Two pathogenic ZRS mutations, 105C>G and 406A>G, have been identified in two Chinese Han families with TPT/PPD, among which the 406A>G mutation was de novo.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D012045	Regulatory Sequences, Nucleic Acid	Nucleic acid sequences involved in regulating the expression of genes.	Nucleic Acid Regulatory Sequences,Regulatory Regions, Nucleic Acid (Genetics),Region, Regulatory,Regions, Regulatory,Regulator Regions, Nucleic Acid,Regulatory Region,Regulatory Regions
D005260	Female		Females
D006228	Hand Deformities, Congenital	Alterations or deviations from normal shape or size which result in a disfigurement of the hand occurring at or before birth.	Congenital Hand Deformities,Congenital Hand Deformity,Deformities, Congenital Hand,Deformity, Congenital Hand,Hand Deformity, Congenital
D006239	Haplotypes	The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.	Haplotype
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013933	Thumb	The first digit on the radial side of the hand which in humans lies opposite the other four.	Thumbs
D017689	Polydactyly	A congenital anomaly of the hand or foot, marked by the presence of supernumerary digits.	Hyperdactyly,Polydactylia,Polydactylism,Hyperdactylies,Polydactylias,Polydactylies,Polydactylisms
D044466	Asian People	Persons having origins in any of the Asian racial groups of the Far East, Southeast Asia, or the Indian subcontinent including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam. Note that OMB category ASIAN is available for United States population groups. Race and ethnicity terms, as used in the federal government, are self-identified social construct and may include terms outdated and offensive in MeSH to assist users who are interested in retrieving comprehensive search results for studies such as in longitudinal studies.	Asian Continental Ancestry Group,Asian Person,Asiatic Race,Mongoloid Race,Asian Peoples,Asian Persons,Asiatic Races,Mongoloid Races,People, Asian,Person, Asian,Race, Asiatic,Race, Mongoloid