Department of Biotechnology and Informatics, BUITEMS, Quetta, Pakistan.
Mol Biol Rep. 2012 May;39(5):6197-201. doi: 10.1007/s11033-011-1438-2. Epub 2012 Jan 5.
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 D17S1583 (7.19 cM), D17S1828 (10.02 cM) and D17S919 (14.69 cM) for an already-reported gene/locus ASPA at chromosome 17p13.2 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 740A→G (p.G274R) in exon 6 of gene ASPA. To our knowledge, this is the first report about Canavan disease on a Pakistani family.
Canavan 病（OMIM 271900）是一种常染色体隐性致死性神经退行性疾病，其特征为脑内海绵样变性。根据诊断，我们纳入了一个高度近亲结婚的巴基斯坦 Canavan 病家族。所有受影响的个体均存在智力低下、大头畸形和运动技能退化、头控不佳、部分视力丧失、肌肉无力以及尿液中 N-乙酰天门冬氨酸浓度升高。采集受影响个体及其正常兄弟姐妹的血液样本，并进行 DNA 纯化处理。通过对已经报道的位于 17p13.2 染色体上的 ASPA 基因/基因座的三个短串联重复标记 D17S1583（7.19 cM）、D17S1828（10.02 cM）和 D17S919（14.69 cM）进行连锁分析，对 Canavan 病进行了分析。在连锁分析中，所有受影响的个体在短串联重复标记上均为纯合子，而正常兄弟姐妹则为杂合子，表明疾病的共分离。对 ASPA 基因（NM_000049）进行测序以进行突变分析。序列分析结果发现，基因 ASPA 的外显子 6 中存在错义替换 740A→G（p.G274R）。据我们所知，这是关于巴基斯坦家族的首例 Canavan 病报告。
