title: Seventeen Novel Mutations in PCCA and PCCB Genes in Indian Propionic Acidemia Patients, and Their Outcomes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1 Center of Medical Genetics, Sir Ganga Ram Hospital , New Delhi, India .|2 Amity Institute of Biotechnology, Amity University , Noida, India .
authors.forename: Deepti
authors.initials: D
authors.lastname: Gupta
authors.affiliation: 1 Center of Medical Genetics, Sir Ganga Ram Hospital , New Delhi, India .
authors.forename: Sunita
authors.initials: S
authors.lastname: Bijarnia-Mahay
authors.affiliation: 1 Center of Medical Genetics, Sir Ganga Ram Hospital , New Delhi, India .
authors.forename: Sudha
authors.initials: S
authors.lastname: Kohli
authors.affiliation: 1 Center of Medical Genetics, Sir Ganga Ram Hospital , New Delhi, India .
authors.forename: Renu
authors.initials: R
authors.lastname: Saxena
authors.affiliation: 1 Center of Medical Genetics, Sir Ganga Ram Hospital , New Delhi, India .
authors.forename: Ratna Dua
authors.initials: RD
authors.lastname: Puri
authors.affiliation: 3 Department of Health Science, University of Fukui , Fukui, Japan .
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shigematsu
authors.affiliation: 4 Department of Pediatrics, Shimane University School of Medicine , Izumo, Japan .
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: 5 Department of Pediatrics, Tohoku University School of Medicine , Sendai, Japan .
authors.forename: Osamu
authors.initials: O
authors.lastname: Sakamoto
authors.affiliation: 6 Department of Pediatrics, All India Institute of Medical Sciences , New Delhi, India .
authors.forename: Neerja
authors.initials: N
authors.lastname: Gupta
authors.affiliation: 6 Department of Pediatrics, All India Institute of Medical Sciences , New Delhi, India .
authors.forename: Madhulika
authors.initials: M
authors.lastname: Kabra
authors.affiliation: 7 Department of Genetics and Fetal Medicine, Fortis Hospitals , Delhi, India .
authors.forename: Seema
authors.initials: S
authors.lastname: Thakur
authors.affiliation: 2 Amity Institute of Biotechnology, Amity University , Noida, India .
authors.forename: Roumi
authors.initials: R
authors.lastname: Deb
authors.affiliation: 1 Center of Medical Genetics, Sir Ganga Ram Hospital , New Delhi, India .
authors.forename: Ishwar Chander
authors.initials: IC
authors.lastname: Verma
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D043586:Methylmalonyl-CoA Decarboxylase / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D056693:Propionic Acidemia / Q000201:enzymology / Q000235:genetics*; D021122:Protein Subunits; D017384:Sequence Deletion
chemical_list: D021122:Protein Subunits; D043586:Methylmalonyl-CoA Decarboxylase