Open AccessWhole genome sequencing reveals translocation breakpoints disrupting TP63 gene underlying split hand/foot malformation in a Chinese family
Author(s) -
Peng Ying,
Yang Shuting,
Xi Hui,
Hu Jiancheng,
Jia Zhengjun,
Pang Jialun,
Liu Jing,
Yu Wenxian,
Tang Chengyuan,
Wang Hua
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1604
Subject(s) - sanger sequencing , genetics , proband , biology , copy number variation , exome sequencing , ectrodactyly , snp array , genetic counseling , penetrance , breakpoint , chromosomal translocation , single nucleotide polymorphism , dna sequencing , genome , gene , genotype , mutation , phenotype , ectodermal dysplasia
Background Split hand/foot malformation (SHFM) is a congenital limb developmental disorder, which impairs the fine activities of hand/foot in the affected individuals seriously. SHFM is commonly inherited as an autosomal dominant disease with incomplete penetrance. Chromosomal aberrations such as copy number variations and translocations have been linked to SHFM. This study aimed to identify the genetic cause for three patients with bilateral hand and foot malformation in a Chinese family. Methods Karyotyping, single‐nucleotide polymorphism (SNP) array, whole exome sequencing, whole genome sequencing, and Sanger sequencing were applied to identify the pathogenic variant. Results Karyotyping revealed that the three patients had balanced reciprocal translocation, 46, XX, t(3;15) (q29;q22). SNP array identified no pathogenic copy number variation in the proband. Trio‐WES (fetus–mother–father) sequencing results revealed no pathogenic variants in the genes related to SHFM. Whole‐genome low‐coverage mate‐pair sequencing (WGL‐MPS), breakpoint PCR, and Sanger sequencing identified the breakpoints disrupting TP63 in the patients, but not in healthy family members. Conclusion This study firstly reports that a translocation breakpoint disrupting TP 63 contributes to the SHFM in a Chinese family, which expands our knowledge of genetic risk and counseling underlying SHFM. It provides a basis for genetic counseling and prenatal diagnosis (preimplantation genetic diagnosis) for this family.