Analysis of a child with SPONASTRIME dysplasia due to compound heterozygous variants of TONSL gene
10.3760/cma.j.cn511374-20230426-00244
- VernacularTitle:TONSL基因复合杂合变异所致海绵状脊椎干骺端发育不良1例患儿的分析
- Author:
Liping ZHU
1
;
Yuzeng HAN
;
Shiyan QIU
;
Na XU
;
Xin ZHANG
;
Yufen LI
;
Li YANG
Author Information
1. 临沂市人民医院儿科，临沂 276000
- Keywords:
TONSL gene;
SPONASTRIME dysplasia;
Spondyloepimetaphyseal dysplasia;
Short stature
- From:
Chinese Journal of Medical Genetics
2024;41(5):577-580
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical features and genetic etiology of a child with SPONASTRIME dysplasia (SD).Methods:A 9-month-old female who had presented at the Linyi People′s Hospital in August 2022 for short stature was selected as the study subject. Clinical data of the child were collected, and whole exome sequencing (WES) was carried out. Sanger sequencing was used for validating the candidate variants.Results:The child has manifested short stature, mid-face hypoplasia, joint laxity, internal knee rotation, irregularities in the metaphysis of long bones, and flat and concave lumbar vertebrae. WES revealed that she has harbored compound heterozygous variants of the TONSL gene, namely c.3088G>T (p.Glu1030*) and c. 3053G>A (p.Arg1018His), which were inherited from her phenotypically normal parents. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 3088G>T variant was classified as likely pathogenic (PVS1+ PM2_Supporting), whilst the c. 3053G>A was classified as a variant of uncertain significance (PM2_Supporting+ PM3+ PP3). Conclusion:The c. 3088G>T and c. 3053G>A compound heterozygous variants of the TONSL gene probably underlay the pathogenesis in this patient. Above finding has facilitated the clinical diagnosis and genetic counseling for her family.
