文献类型：期刊文献

英文题名：Immune skeletal dysplasia with neurodevelopmental abnormalities caused by a novel variant of EXTL3 gene in a Chinese family

作者：Tian, Xinyuan[1,2];Zhang, Xiaoni[3];Zhang, Qinghua[1];Chen, Xue[1];Zhou, Bingbo[1];Ma, Panpan[1];Zheng, Lei[1];Hao, Shengju[1];Ling, Junhe[2];Zhang, Chuan[1];Hui, Ling[1]

第一作者：Tian, Xinyuan;田小雨

通信作者：Zhang, C[1];Hui, L[1]

机构：[1]Gansu Prov Matern & Child Care Hosp, Ctr Med Genet, Gansu Prov Clin Res Ctr Birth Defects & Rare Dis, Lanzhou, Peoples R China;[2]Gansu Univ Chinese Med, Sch Publ Hlth, Lanzhou, Peoples R China;[3]Gansu Prov Matern & Child Care Hosp, Ctr Early Childhood Dev, Lanzhou, Peoples R China

第一机构：Gansu Prov Matern & Child Care Hosp, Ctr Med Genet, Gansu Prov Clin Res Ctr Birth Defects & Rare Dis, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Matern & Child Care Hosp, Ctr Med Genet, Gansu Prov Clin Res Ctr Birth Defects & Rare Dis, Lanzhou, Peoples R China.

年份：2024

卷号：12

期号：1

外文期刊名：MOLECULAR GENETICS & GENOMIC MEDICINE

收录：;Scopus(收录号：2-s2.0-85178070296);WOS:【SCI-EXPANDED(收录号:WOS:001109841000001)】；

基金：This work was supported by the Science and Technology Program of Gansu Province (Grant No. 21JR7RA680), the National Key Research and Development Program of China (Grant No. 2016YFC1000307), the Lanzhou Science and Technology Plan Project (Grant No. 2021-1-182), the National Population and Reproductive Health Science Data Center (Grant No. 2005DKA32408), the Lanzhou Science and Technology Plan Project (Grant No. 2022-5-81), and the Lanzhou Talent Innovation and Entrepreneurship Project (Grant No. 2018-RC-95).

语种：英文

外文关键词：EXTL3 gene; immune skeletal dysplasia with neurodevelopmental abnormalities; immune system function abnormalities; neurodevelopmental deficits; skeletal abnormalities

摘要：Background: Immune skeletal dysplasia with neurodevelopmental abnormalities (ISDNA) is an extremely rare, autosomal recessive genetic disorder characterized by various skeletal abnormalities, neurodevelopmental deficits, and abnormal immune system function. ISDNA is caused by variation in the exostosin-like 3 (EXTL3) gene, located on chromosome 8p21.2, whose primary function is the biosynthesis of heparan sulfate (HS) skeleton structure. Only a few variations in the EXTL3 gene have been discovered so far. In these years of development, many pathogenic variants in genetic diseases with genetic and phenotypic heterogeneity have been investigated using whole-exome sequencing (WES) technology.Methods: In this research, a novel EXTL3 variant was first detected in a patient using WES, which was validated from Sanger sequencing in this family. Family history and clinical information were then collected through comprehensive medical examinations and genetic counseling. In silico prediction was then utilized to confirm the pathogenicity of the variant.Results: A novel homozygous variant, NM_001440: c.2015G>A (p.Arg672Gln) in the EXTL3 gene, was identified using WES, which has never been reported before. Sanger sequencing was performed to confirm that the variant segregated with the disease within the family.Conclusion: This research identified a novel pathogenic variant in the EXTL3 gene responsible for ISDNA in a Chinese family. It showed the potential diagnostic role of WES in ISDNA, expanded the EXTL3 gene variation spectrum, and demonstrated that the diagnosis of ISDNA using WES is feasible and effective. More comprehensive genetic counseling and precise prenatal diagnosis for the next pregnancy can also be provided to families with genetic disorders.