A missense mutation (p.G274R) in gene ASPA causes Canavan disease in a Pakistani family.

[canavan disease]

Canavan disease (OMIM 271900 ) is an autosomal recessive lethal neurodegenerative disorder characterized by spongy degeneration of the brain . A highly consanguineous Pakistani family with Canavan disease was enrolled on the basis of diagnosis . All the affected individuals have mental retardation , megalocephaly and degradation of motor skills , poor head control , partial vision loss , weakness of the muscles and raised urinary concentration of N-acetyl aspartic acid in the urine . Blood samples were collected from affected as well as normal siblings and processed for DNA purification . Linkage analysis was performed by typing three short tandem repeat markers D 17 S 1583 (7 .19 Â cM ), D 17 S 1828 (10 .02 Â cM ) and D 17 S 919 (14 .69 Â cM ) for an already-reported gene /locus ASPA at chromosome 17 p 13 .2 causing Canavan disease . During linkage analysis , all the affected individuals were homozygous for short tandem repeat markers while the normal siblings were heterozygous showing co -segregation of the disease . Gene ASPA (NM _000049 ) was undertaken to sequence for mutation analysis . As a result of sequence analysis , we found missense substitution 740 A â†’G (p .G 274 R ) in exon 6 of gene ASPA . To our knowledge , this is the first report about Canavan disease on a Pakistani family .