[ZRS mutations in two Chinese Han families featuring triphalangeal thumbs and preaxial polydactyly].
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.
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.
Ximeng
X
Zhao
Wei
W
Yang
Miao
M
Sun
Xue
X
Zhang
D044466:Asian People / Q000235:genetics*; D005260:Female; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D017689:Polydactyly / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D013933:Thumb / Q000002:abnormalities*