Arunachalam Arun Kumar, Aboobacker Fouzia N, Sampath Eswari, Devasia Anup J, Korula Anu, George Biju, Edison Eunice Sindhuvi
Department of Haematology, Christian Medical College, Vellore, Tamil Nadu 632517 India.
Indian J Hematol Blood Transfus. 2024 Jul;40(3):494-503. doi: 10.1007/s12288-023-01732-4. Epub 2024 Jan 12.
Osteopetrosis is a clinically and genetically heterogeneous group of inherited bone disorders that is caused by defects in osteoclast formation or function. Treatment options vary with the disease severity and an accurate molecular diagnosis helps in prognostication and treatment decisions. We investigated the genetic causes of osteopetrosis in 31 unrelated patients of Indian origin. Screening for the genetic variants was done by Sanger sequencing or next generation sequencing in 48 samples that included 31 samples from index patients, 16 from parents' and 1 chorionic villus sample. A total of 30 variants, including 29 unique variants, were identified in 26 of the 31 patients in the study. was the most involved gene (n = 14) followed by (n = 4) and (n = 3). A total of 17 novel variants were identified. Prenatal diagnosis was done in one family and the foetus showed homozygous c.807 + 2T > G variant in . Molecular diagnosis of osteopetrosis aids in therapeutic decisions including the need for a stem cell transplantation and gives a possible option of performing prenatal diagnosis in affected families. Further studies would help in understanding the genetic etiology in patients where no variants were identified.
The online version contains supplementary material available at 10.1007/s12288-023-01732-4.
骨硬化症是一组临床和遗传异质性的遗传性骨疾病，由破骨细胞形成或功能缺陷引起。治疗方案因疾病严重程度而异，准确的分子诊断有助于预后评估和治疗决策。我们调查了31名印度裔无关患者骨硬化症的遗传原因。通过桑格测序或下一代测序对48个样本进行基因变异筛查，其中包括31个索引患者样本、16个父母样本和1个绒毛膜绒毛样本。在该研究的31名患者中的26名患者中，共鉴定出30个变异，包括29个独特变异。 是受累最多的基因（n = 14），其次是 （n = 4）和 （n = 3）。共鉴定出17个新变异。在一个家庭中进行了产前诊断，胎儿在 中显示纯合的c.807+2T>G变异。骨硬化症的分子诊断有助于治疗决策，包括是否需要进行干细胞移植，并为受影响家庭提供了进行产前诊断的可能选择。进一步的研究将有助于了解未鉴定出变异的患者的遗传病因。
在线版本包含可在10.1007/s12288-023-01732-4获取的补充材料。
