Description:
<jats:title>Abstract</jats:title><jats:p>Osteogenesis imperfecta (OI) is a group of inherited disorders with increased bone fragility and wide genetic heterogeneity. We report the outcome of clinical exome sequencing validated by Sanger sequencing in clinically diagnosed 54 OI patients in Indian population. In 52 patients, we report 20 new variants involving both dominant and recessive OI‐specific genes and correlate these with phenotypes. <jats:italic>COL1A1</jats:italic> and <jats:italic>COL1A2</jats:italic> gene variants were identified in 44.23%, of which 28.84% were glycine substitution abnormalities. Two novel compound heterozygous variants in the <jats:italic>FKBP10</jats:italic> gene were seen in two unrelated probands. A novel heterogeneous duplication of chromosomal region <jats:italic>chr17: 48268168–48278884</jats:italic> from exons 1–33 of the <jats:italic>COL1A1</jats:italic> gene was found in one proband. In five probands, there were additional variants in association with OI. These were <jats:italic>ANO5</jats:italic> in association with <jats:italic>CRTAP</jats:italic> in two probands of the same family causing gnathodiaphyseal dysplasia, <jats:italic>COL5A2</jats:italic> with <jats:italic>LEPRE1</jats:italic> causing Ehlers Danlos syndrome, <jats:italic>COL11A1</jats:italic> in addition to <jats:italic>COL1A1</jats:italic> causing Stickler syndrome, and a previously unreported combination of <jats:italic>SLC34A1</jats:italic> gene variant with <jats:italic>FKBP10</jats:italic> leading to Fanconi renal tubular syndrome type II. Our findings demonstrate the efficacy of clinical exome sequencing in screening OI patients, classifying its subtypes, and identifying associated disorders in consanguineous populations.</jats:p>