Clinical phenotype and genetic analysis of a child with short stature and multiple skeletal dysplasia
10.3760/cma.j.cn511374-20230511-00277
- VernacularTitle:身材矮小伴多发性骨骼发育不良1例患儿的临床表型与遗传学分析
- Author:
Yongxue LYU
1
;
Fengfeng QI
;
Zhenghua FEI
;
Hanlu GAO
;
Chunjian GU
Author Information
1. 湖州市妇幼保健院儿童保健部，湖州 313000
- Keywords:
ACAN gene;
Frameshifting variant;
Familial short stature;
Skeletal malformation;
Midfacial dysplasia;
Pectus carinatum
- From:
Chinese Journal of Medical Genetics
2024;41(2):244-249
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the clinical phenotype and genetic basis for a child featuring familial short stature.Methods:A child who was admitted to Huzhou Maternal and Child Health Care Hospital on October 7, 2021 for growth retardation and pectus carinatum was selected as the study subject. Physical exam and medical imaging was performed. The child was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 1-year-old male, had manifested with slightly short stature ( Z = -2.03), midfacial dysplasia, and multiple skeletal dysplasia such as pectus carinatum, irregular vertebral morphology, and defect of lumbar anterior bones. His mother, maternal grandmother and great-maternal grandfather also had short stature. WES revealed that the child has harbored a heterozygous c. 2858dupA (p.Asp953GlufsTer476) frameshifting variant of the ACAN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 2858dup (p.Sp953Glufster476) variant was classified as likely pathogenic (PVS1+ PM2_Supporting). The patient has shown marked improved height after receiving 11 months of treatment with human recombinant growth hormone (supplemental dose) starting from 20 months of age. Conclusion:The ACAN: c. 2858dup (p.Asp953GlufsTer476) variant probably underlay the pathogenesis of short stature in this child.
