A Chinese patient with Rothmund–Thomson syndrome

• Published in: Molecular genetics & genomic medicine 2024-01, Vol.12 (1), p.e2347-n/a
• Main Authors: Zeng, Juan, Li, Jiayi, Liu, Yuwei, Liang, Rui, Wang, Lin, Zhou, Qing, Sun, Jinghua, Liu, Zhongzhen, Wang, Wen‐Jing, Zhu, Sujun
• Format: Article
• Language: English
• Subjects: Amniotic fluid; Birth weight; China; Cohort analysis; Erythema; Fetuses; Frameshift Mutation; Gene sequencing; Genes; Genetic screening; Genetic testing; Genomes; Genomics; Hair; Hereditary diseases; Humans; Low birth weight; Mutation; Nonsense mutation; pathogenic compound heterozygous mutations; Phenotype; Phenotypes; Placenta; Polymorphism; Pregnancy; Prenatal diagnosis; Proteins; RECQL4; Rothmund-Thomson syndrome; Rothmund-Thomson Syndrome - diagnosis; Rothmund-Thomson Syndrome - genetics; Rothmund-Thomson Syndrome - pathology; Ultrasonic imaging; Umbilical cord; Whole genome sequencing
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.2347

Introduction Rothmund–Thomson syndrome (RTS) is a rare autosomal recessive disorder that has been reported in all ethnicities, with several identifiable pathogenic variants. There have been reported cases indicating that RTS may lead to low birth weight in fetuses, but specific data on the fetal period are lacking. Genetic testing for RTS II is currently carried out by identifying pathogenic variants in RECQL4. Methods In order to determine the cause, we performed whole‐genome sequencing (WGS) analysis on the patient and his parents. Variants detected by WGS were confirmed by Sanger sequencing and examined in family members. Results After analyzing the WGS data, we found a heterozygous nonsense mutation c.2752G>T (p.Glu918Ter) and a novel frameshift insertion mutation c.1547dupC (p.Leu517AlafsTer23) of RECQL4, which is a known pathogenic/disease‐causing variant of RTS. Further validation indicated these were compound heterozygous mutations from parents. Conclusion Our study expands the mutational spectrum of the RECQL4 gene and enriches the phenotype spectrum of Chinese RTS patients. Our information can assist the patient's parents in making informed decisions regarding their future pregnancies. This case offers a new perspective for clinicians to consider whether to perform prenatal diagnosis. Rothmund–Thomson syndrome (RTS) is associated with intrauterine growth restriction during pregnancy. This case offers a new perspective for clinicians to consider whether to perform prenatal diagnosis and expands the mutational spectrum of the RECQL4 gene. Our information can assist the patient's parents in making informed decisions regarding their future pregnancies.