![]() Human subjects involved had legal capacity to give voluntary consent. The protocol was approved by the Institutional Review Board of National Cheng Kung University Hospital (IRB Approval No. The clinical investigations were conducted according to the principles expressed in the Nuremberg Code and Declaration of Helsinki. The cellular function of primary cells derived from the patients was compared with that of normal subjects. This mutation site is first reported as a pathogenic mutation. Schwartz–Jampel syndrome is a rare autosomal recessive disease with a prevalence of G on HSPG2 causing a p.Cys375Trp change in domain II of the perlecan core protein from two familial cases. Patients with this mutation showed more neuromuscular instability and relatively mild skeletal abnormality comparing with previously reported cases. At cellular levels, mutant primary fibroblasts had reduced levels of secreted perlecan and impaired migration ability but normal capability of proliferation. Short exercise test for myotonia showed Fournier pattern I. Needle electromyography revealed extensive complex repetitive discharges and multiple polyphasic motor unit action potentials in axial and limb muscles at rest. ![]() Various in silico software applications predicted the mutation to be pathogenic. The pathogenic nature of this missense mutation was demonstrated by in silico pathogenicity assessment, clinical presentations, and cellular function of primary fibroblast derived from patients. This mutation carried by the asymptomatic parents was previously registered in a single-nucleotide polymorphism database of the National Institutes of Health as a coding sequence variant rs543805444. Herein, we identified a new pathogenic mutation site (NM_005529.6:c.1125C>G p.Cys375Trp) of HSPG2 leading to Schwartz–Jampel syndrome by whole-exome sequencing. Its cardinal symptoms are skeletal dysplasia and neuromuscular hyperactivity. Schwartz–Jampel syndrome is a rare autosomal recessive disease caused by mutation in the heparan sulfate proteoglycan 2 ( HSPG2) gene. 6Institute of Basic Medical Sciences and Department of Biochemistry and Molecular Biology, National Cheng Kung University College of Medicine, Tainan, Taiwan.5Department of Genomic Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.4Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.3Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.2Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.1Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.Po-Yu Lin 1, Jia-Horung Hung 2,3, Chao-Kai Hsu 4,5, Yao-Tsung Chang 6 and Yuan-Ting Sun 1,5 *
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