Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics · 2026
[Clinical characteristics and genetic analysis of a child with Dyggve-Melchior-Clausen syndrome due to variant of DYM gene].
СтатьяКлинический случайАннотация на английскомНазвание и аннотация: Перевод в очереди
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Liu Haiyi, Zhang Qianwen, Chang Guoying, Yang Fan, Li Juan, Li Qun, Gu Shili, Wang Zhigang, Yao Ruen, Yu Tingting, Wang Xiumin
Аннотация
OBJECTIVE: To analyze the clinical phenotype and genetic etiology of patients with Dyggve-Melchior-Clausen syndrome (DMC syndrome).
METHODS: A child with DMC syndrome diagnosed at Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University in August 2020 was selected as study subject. A retrospective analysis was carried out to collect the proband's clinical data. Peripheral blood samples was collected from the proband and his parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out. Candidate variants were validated within the family by Sanger sequencing. Pathogenicity of candidate variants was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the center (Ethics No.: SCMCIRB-K2023024-1).
RESULTS: The proband, a 5-year-and-7-month-old girl, presented with short stature (height: -5.5 s) and intellectual disability. Physical examination revealed microcephaly (head circumference: -3.5 s), coarse facial features, long philtrum, pigeon chest, and brachydactyly of both hands. Laboratory findings revealed normal serum insulin-like growth factor-1 (IGF-1) levels (168 ng/mL). Imaging analysis demonstrated dysplasia of corpus callosum and spondyloepiphyseal dysplasia in the proband. WES revealed that she has harbored compound heterozygous variants of the DYM gene, namely c.312-313del (p.His104Glnfs*29) and c.1274A>T (p.Tyr425Phe). Both variants were unreported previously and inherited from her parents who were phenotypically normal. Based on guidelines from the ACMG, the DYM gene variant c.312-313del (p.His104Glnfs*29) was classified as pathogenic (PVS1+PM2_Supporting+PP3+PP4_supporting), while the c.1274A>T (p.Tyr425Phe) variant was classified as likely pathogenic (PM2_Supporting+PP3+PP1+PP4_supporting). By following the pre-set literature search strategy, a total of 20 articles were included, which involved a total of 73 cases of DYM gene variants leading to DMC syndrome. Among these, only one family case was documented in China. Together with proband from this study, a total of 74 DMC syndrome patients due DYM gene variants were included for a comprehensive analysis of clinical phenotypes and genetic characteristics. The age at the time of reporting ranged from 1 to 60 years. The main clinical manifestations included intellectual disability, short stature, and spondyloepiphyseal dysplasia, followed by microcephaly and coarse facial features. By genetic testing, c.1877delA variant was the most common mutation at the nucleotide level.
CONCLUSION: The c.312-313del/c.1274A>T compound heterozygous variants of the DYM gene probably underlay the pathogenesis of DMC syndrome in this proband. Above finding has expanded the mutational and phenotypic spectra of the DMC syndrome.
METHODS: A child with DMC syndrome diagnosed at Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University in August 2020 was selected as study subject. A retrospective analysis was carried out to collect the proband's clinical data. Peripheral blood samples was collected from the proband and his parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out. Candidate variants were validated within the family by Sanger sequencing. Pathogenicity of candidate variants was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the center (Ethics No.: SCMCIRB-K2023024-1).
RESULTS: The proband, a 5-year-and-7-month-old girl, presented with short stature (height: -5.5 s) and intellectual disability. Physical examination revealed microcephaly (head circumference: -3.5 s), coarse facial features, long philtrum, pigeon chest, and brachydactyly of both hands. Laboratory findings revealed normal serum insulin-like growth factor-1 (IGF-1) levels (168 ng/mL). Imaging analysis demonstrated dysplasia of corpus callosum and spondyloepiphyseal dysplasia in the proband. WES revealed that she has harbored compound heterozygous variants of the DYM gene, namely c.312-313del (p.His104Glnfs*29) and c.1274A>T (p.Tyr425Phe). Both variants were unreported previously and inherited from her parents who were phenotypically normal. Based on guidelines from the ACMG, the DYM gene variant c.312-313del (p.His104Glnfs*29) was classified as pathogenic (PVS1+PM2_Supporting+PP3+PP4_supporting), while the c.1274A>T (p.Tyr425Phe) variant was classified as likely pathogenic (PM2_Supporting+PP3+PP1+PP4_supporting). By following the pre-set literature search strategy, a total of 20 articles were included, which involved a total of 73 cases of DYM gene variants leading to DMC syndrome. Among these, only one family case was documented in China. Together with proband from this study, a total of 74 DMC syndrome patients due DYM gene variants were included for a comprehensive analysis of clinical phenotypes and genetic characteristics. The age at the time of reporting ranged from 1 to 60 years. The main clinical manifestations included intellectual disability, short stature, and spondyloepiphyseal dysplasia, followed by microcephaly and coarse facial features. By genetic testing, c.1877delA variant was the most common mutation at the nucleotide level.
CONCLUSION: The c.312-313del/c.1274A>T compound heterozygous variants of the DYM gene probably underlay the pathogenesis of DMC syndrome in this proband. Above finding has expanded the mutational and phenotypic spectra of the DMC syndrome.