Genetic analysis of a congenital split‑hand/split‑foot malformation 4 pedigree

Yang,Xiao; Lin,Xinfu; Zhu,Yaobin; Luo,Jiewei; Lin,Genhui

doi:10.3892/mmr.2018.8838

Genetic analysis of a congenital split‑hand/split‑foot malformation 4 pedigree

Authors:
- Xiao Yang
- Xinfu Lin
- Yaobin Zhu
- Jiewei Luo
- Genhui Lin
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Affiliations: Teaching and Research Office of Medical Cosmetology, Department of Management, Fujian Health College, Fuzhou, Fujian 350001, P.R. China, Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China, Department of Traditional Chinese Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
Published online on: March 29, 2018 https://doi.org/10.3892/mmr.2018.8838
Pages: 7553-7558
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In the present study whole-exome sequencing using the Complete Genomics platform was employed to scan a proband from a split‑hand/split‑foot malformation (SHFM) 4 family. The missense mutation c.728G>A (p.Arg243Gln) in the TP63 gene was revealed to be associated with SHFM. Sanger sequencing confirmed the sequences of the proband and his father. The father was diagnosed with SHFM and harbored a CGG‑to‑CAG mutation in exon 5, which produced a R243Q substitution in the zinc binding site and dimerization site of TP63. The R243Q mutation was predicted to be pathogenic by PolyPhen‑2. The proband, who was diagnosed with four digit SHFM, exhibited a more severe phenotype. X‑ray analysis returned the following results: Absence of third phalange bilaterally and third metacarpus of the left hand; absence of the second toes bilaterally and partial third toes; and partial fusion of the second, third and metatarsal bones of the right side with deformity of the second metatarsal of the right side. Osteochondroma was present in the fourth proximal radial metacarpal of the left hand and the basal and proximal parts of the second metatarsal of the right side. The proband’s father had five digits in both feet. These results indicate that the R243Q mutation produces a novel phenotype named SHFM4. The present study revealed that the R243Q mutation in the TP63 gene produced a novel phenotype named SHFM4, thereby demonstrating the mutational overlap between ectrodactyly‑ectodermal dysplasia‑cleft syndrome and SHFM4.

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