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. TCIRG1 was the most involved gene (n = 14) followed by TNFRSF11A (n = 4) and CLCN7 (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 TCIRG1. 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.

骨石症是一组临床和遗传异质性遗传性骨疾病，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测和治疗决策。我们调查了 31 名无关的印度裔患者石骨症的遗传原因。通过桑格测序或下一代测序对 48 个样本进行遗传变异筛查，其中包括 31 个来自指示患者的样本、16 个来自父母的样本和 1 个绒毛膜绒毛样本。在该研究的 31 名患者中，有 26 名患者共鉴定出 30 种变异，其中包括 29 种独特变异。TCIRG1是最相关的基因 (n = 14)，其次是TNFRSF11A (n = 4) 和CLCN7 (n = 3)。总共鉴定出 17 个新变体。1个家庭进行产前诊断，胎儿TCIRG1显示纯合c.807+2T>G变异。石骨症的分子诊断有助于治疗决策，包括是否需要干细胞移植，并为受影响的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发现变异的患者的遗传病因。