Genetic analysis of a fetus with Rhizomelic skeletal dysplasia
10.3760/cma.j.cn511374-20230523-00309
- VernacularTitle:肢根型骨发育不良1例胎儿的遗传学分析
- Author:
Yang DING
1
;
Ting WANG
;
Jingjing XIANG
Author Information
1. 南京医科大学附属苏州医院·苏州市立医院生殖与遗传中心，苏州 215002
- Keywords:
Rhizomelic skeletal dysplasia;
LBR gene;
Pelger-Huёt anomaly;
Whole exome sequencing
- From:
Chinese Journal of Medical Genetics
2024;41(7):844-848
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical features and genetic basis for a fetus featuring Rhizomelic skeletal dysplasia.Methods:A fetus diagnosed at the Reproductive and Genetic Center of Suzhou Municipal Hospital in November 2020 was selected as the study subject. Whole exome sequencing (WES) was carried out for the fetus and its parents. Candidate variants were verified by Sanger sequencing. Peripheral blood smears of both parents were also examined.Results:The fetus was found to have a small chest and short limbs, which had suggested skeletal dysplasia. Genetic testing revealed that the fetus has harbored compound heterozygous variants of the LBR gene, including a paternally derived c. 1687+ 1G>A and a maternally derived c. 1757G>A (p.Arg586His). The blood smear of the father showed Pelger-Huёt anomaly with hyposegmentation of neutrophil nuclei, while the neutrophils of the mother appeared to be normal. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), the c. 1757G>A (p.Arg586His) variant was classified as likely pathogenic (PM3_Strong+ PM2_Supporting+ PP3), and so was the c. 1687+ 1G>A variant (PVS1-Moderate+ PM3+ PM2-Supporting+ PP4). Conclusion:The compound heterozygous variants of the LBR gene probably underlay the pathogenesis of skeletal dysplasia in this fetus.
