A child with microcephaly, growth restriction, and increased sister chromatid exchange-2 caused by TOP3A gene variations
10.3760/cma.j.cn101070-20240906-00577
- VernacularTitle:TOP3A基因变异导致小头畸形-生长延迟-姐妹染色体互换率增高2型1例
- Author:
Yucan ZHENG
1
;
Mei LI
1
;
Yu JIN
1
;
Kunlong YAN
1
Author Information
1. 南京医科大学附属儿童医院消化科，南京 210008
- Publication Type:Journal Article
- Keywords:
TOP3A gene;
Microcephaly, growth restriction, and increased sister chromatid exchange-2;
Whole-exome sequencing
- From:
Chinese Journal of Applied Clinical Pediatrics
2025;40(6):461-464
- CountryChina
- Language:Chinese
-
Abstract:
The clinical features and genetic variation of a patient with microcephaly, growth restriction, and increased sister chromatid exchange-2, who was treated in the Department of Gastroenterology, Children′s Hospital of Nanjing Medical University in April 2024 were analyzed, and the pathogenic cause was identified.The clinical data of the patient were collected, and the genomic DNA was extracted from the peripheral blood of the proband and his parents.Gene detection was conducted through whole-exome sequencing, and candidate variants were verified by Sanger sequencing and bioinformatics analysis.The proband presented with intrauterine growth restriction, retarded growth and development, microcephaly, and premature ageing-like facial features.Gene sequencing showed novel compound heterozygous variations c. 1333T>C (p.C445R) and c. 2345dup (p.P783Afs*3) in the proband.Both variants are conserved, and various bioinformatics tools predict them to be deleterious.The compound heterozygous variant (c.1333T>C/c.2345dup) in the TOP3A gene is the likely etiology of the patient′s condition.These two novel variants expand the spectrum of known TOP3A gene variants and provide a basis for genetic counseling for the family.
