Clinical characteristics of a SPONASTRIME-type spondyloepimetaphyseal dysplasia family and analysis of TONSL gene mutation
10.3760/cma.j.cn311282-20221212-00687
- VernacularTitle:一个SPONASTRIME型脊椎干骺端发育不良家系的临床特点及TONSL基因突变分析
- Author:
Mali LI
1
;
Jia LI
;
Shichao QIU
;
Chao LIU
;
Na SONG
;
Zhihua WANG
Author Information
1. 西安市儿童医院内分泌遗传代谢科 710003
- Keywords:
Spondyloepimetaphyseal dysplasia;
Special facial features;
Growth hormone deficiency;
Gene mutation
- From:
Chinese Journal of Endocrinology and Metabolism
2023;39(10):826-832
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To provide molecular evidence for clinical diagnosis and genetic counseling by analyzing the clinical characteristics and identifying the pathogenic genes in a SPONASTRIME-type spondyloepimetaphyseal dysplasia(SEMDSP)family.Methods:Clinical data of the family members was collected and analyzed. Case 2 was identified as the proband for whole-exome sequencing and variant analysis. Suspected variants were validated across family numbers using Sanger sequencing.Results:The two affected individuals in this family, a brother and a sister, both presented as short stature. The initial diagnosis for the sister(case 1)was made at the age of 4 years and 2 months(height: 88.6 cm), and for the brother(case 2)at 4 years and 4 months(height: 81.6 cm). Both individuals exhibited distinctive facial features, including frontal bossing, midface hypoplasia with depressed nasal bridge, upturned nostrils, ocular hypertelorism, and epicanthus, thick hair, short lingual frenulum, stubby fingers and palms, and absence of scoliosis. The parents displayed normal phenotypes. Laboratory tests indicated growth hormone deficiency in both affected individuals. Imaging studies revealed significant bone age delay in case 2, while case 1 showed longitudinal striations at the distal radius but with bone age matching their actual age(5 years and 11 months). Despite receiving recombinant human growth hormone treatment, both patients had inadequate responses. Genetic testing identified compound heterozygous mutations in the TONSL gene shared by the two siblings. These mutations included a paternally inherited c. 1291-14_1291-11delCCTC and a maternally inherited c. 1909_1920delACGCTGCAGCAG. Notably, SEMDSP families have not been reported in China, and the c. 1909_1920delACGCTGCAGCAG mutation is a novel variant.Conclusion:Two patients were diagnosed as spondyloepimetaphyseal dysplasia, SPONASTRIME type, and the compound heterozygous variant was the genetic cause of this family.
