title: Molecular characterisation and prenatal diagnosis of Asparto-acylase deficiency (Canavan disease)--report of two novel and two known mutations from the Indian subcontinent.
abstract: OBJECTIVE
  To establish a technique for mutation identification and prenatal screening in confirmed cases of Canavan disease.
  
  
  METHODS
  Mutations in ASPA gene were identified by sequencing. Six exons of ASPA gene were amplified using intronic primers flanking the exons and then sequenced on ABI 3500Dx automated unit. This technique was used to identify mutations in three cases of Canavan disease. Prenatal diagnosis was performed in two families.
  
  
  RESULTS
  Two reported mutations c.162 C > A (p.Asn54Lys) and c.859 G > A (p.Ala287Thr) were identified in two different cases of Canavan disease. Third case was compound heterozygous for two novel mutations (c.728 T > G, p.Ile243Ser; c.902 T > C, p.Leu301Pro). Prenatal diagnosis was performed in three pregnancies in two families, two affected fetuses and one unaffected fetus were identified.
  
  
  CONCLUSIONS
  Molecular characterization of Canavan disease helps identify the cause at genetic level, thus confirming diagnosis and enabling identification of carriers in the family. Though enzyme assay and NAA measurement allows diagnosis and prenatal diagnosis of Canavan diasease, molecular methods have the advantage of bringing accuracy in prenatal testing with an earlier result. This is the first case report of mutation studies in Canavan disease from Indian subcontinent.
authors.affiliation: Center of Medical Genetics, Sir Ganga Ram Hospital, New Delhi, India. Bijarnia@gmail.com
authors.forename: Sunita
authors.initials: S
authors.lastname: Bijarnia
authors.forename: Sudha
authors.initials: S
authors.lastname: Kohli
authors.forename: Ratna Dua
authors.initials: RD
authors.lastname: Puri
authors.forename: Rintu J
authors.initials: RJ
authors.lastname: Jacob
authors.forename: Renu
authors.initials: R
authors.lastname: Saxena
authors.forename: Anil
authors.initials: A
authors.lastname: Jalan
authors.forename: Eric A
authors.initials: EA
authors.lastname: Sistermans
authors.forename: Saqib
authors.initials: S
authors.lastname: Mahmood
authors.forename: Ishwar Chander
authors.initials: IC
authors.lastname: Verma
mesh_terms: D000581:Amidohydrolases / Q000235:genetics*; D017825:Canavan Disease / Q000175:diagnosis* / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D009154:Mutation; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*
chemical_list: D000581:Amidohydrolases; C019751:aspartoacylase