Characterization of Clinical and Laboratory Profiles of the Deletional α2-Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA- -) in an Indian Population.

α-Thalassemia (α-thal) is characterized by large deletions involving the variable regions of α2 and/or α1 genes. Nondeletional mutations and polyadenylation (polyA) signal sequence motif mutations are less common. In this retrospective study, we describe a fragment length analysis-based polymerase chain reaction (PCR) assay for screening the T(Indian) (AATAAA > AATA- -; HBA2: c.*93_*94delAA) polyA signal deletion along with its clinical and laboratory presentation in 21 patients. Most of the patients were diagnosed in early adulthood with a clinical presentation ranging from asymptomatic in the heterozygous state to severe Hb H disease with a prominent hemolytic component in the homozygous state. On genetic analysis, 14 patients were found to be homozygotes, five were compound heterozygotes and two were heterozygotes. Thus, the T(Indian) polyA signal deletion is common in the Indian population and should be screened for in patients with nondeletional α-thal mutations.

Molecular Heterogeneity of Osteopetrosis in India: Report of 17 Novel Variants.

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. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01732-4.