Deepti Gupta1,2, Sunita Bijarnia-Mahay1, Sudha Kohli1, Renu Saxena1, Ratna Dua Puri1, Yosuke Shigematsu3, Seiji Yamaguchi4, Osamu Sakamoto5, Neerja Gupta6, Madhulika Kabra6, Seema Thakur7, Roumi Deb2, Ishwar Chander Verma1. 1. 1 Center of Medical Genetics, Sir Ganga Ram Hospital , New Delhi, India . 2. 2 Amity Institute of Biotechnology, Amity University , Noida, India . 3. 3 Department of Health Science, University of Fukui , Fukui, Japan . 4. 4 Department of Pediatrics, Shimane University School of Medicine , Izumo, Japan . 5. 5 Department of Pediatrics, Tohoku University School of Medicine , Sendai, Japan . 6. 6 Department of Pediatrics, All India Institute of Medical Sciences , New Delhi, India . 7. 7 Department of Genetics and Fetal Medicine, Fortis Hospitals , Delhi, India .
Abstract
AIMS: The goal of this study was to identify mutations in the propionyl-CoA carboxylase alpha subunit (PCCA) and propionyl-CoA carboxylase beta subunit (PCCB) genes, and to assess their effects on propionic academia (PA) patients. METHODOLOGY: Twenty-five Indian children with PA were enrolled in this study. Bidirectional Sanger sequencing was performed on both the coding and flanking regions of the PCCA and PCCB genes and the chromatograms were analyzed. Bioinformatic tools were used to classify novel variations into pathogenic or benign. RESULTS: The majority of the cases (19/25, 76%) were of the early-onset (<90 days of age) type and 5 were of the late-onset type. The majority of patients had mutations in the PCCA gene (18/25). A total of 26 mutations were noted: 20 in the PCCA gene and 6 in PCCB gene. Seventeen mutations were novel (14 in PCCA and 3 in PCCB). The SNP c.937C>T (p.Arg313Ter), was noted in 9/36 (25%) alleles in the PCCA gene. All of the children were symptomatic and only three survived who are doing well with no major disabilities. CONCLUSION: The spectrum of mutations in the PCCA and PCCB genes among Indians is distinct from other populations. The absence of a common mutation signifies the heterogeneity and admixture of various subpopulations. These findings also suggest that individuals of Indian origin may not benefit from the mutation-based "carrier screening panels" offered by many genetic laboratories.
AIMS: The goal of this study was to identify mutations in the propionyl-CoA carboxylase alpha subunit (PCCA) and propionyl-CoA carboxylase beta subunit (PCCB) genes, and to assess their effects on propionic academia (PA) patients. METHODOLOGY: Twenty-five Indian children with PA were enrolled in this study. Bidirectional Sanger sequencing was performed on both the coding and flanking regions of the PCCA and PCCB genes and the chromatograms were analyzed. Bioinformatic tools were used to classify novel variations into pathogenic or benign. RESULTS: The majority of the cases (19/25, 76%) were of the early-onset (<90 days of age) type and 5 were of the late-onset type. The majority of patients had mutations in the PCCA gene (18/25). A total of 26 mutations were noted: 20 in the PCCA gene and 6 in PCCB gene. Seventeen mutations were novel (14 in PCCA and 3 in PCCB). The SNP c.937C>T (p.Arg313Ter), was noted in 9/36 (25%) alleles in the PCCA gene. All of the children were symptomatic and only three survived who are doing well with no major disabilities. CONCLUSION: The spectrum of mutations in the PCCA and PCCB genes among Indians is distinct from other populations. The absence of a common mutation signifies the heterogeneity and admixture of various subpopulations. These findings also suggest that individuals of Indian origin may not benefit from the mutation-based "carrier screening panels" offered by many genetic laboratories.