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

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Abstract

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.

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Acknowledgments

We wish to thank all the participants during this research. This study was supported by Higher Education Commission (HEC) of Pakistan through research grant (20-1138/R&d/08/2383) under program of NRPU.

Electronic databases

Online Mendelian inheritance in Man (http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim). Marshfield genetic map (http://research.marshfieldclinic.org/). Primer3 web site (http://frodo.wi.mit.edu.cgi-bin/primer3_www.cgi).

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Authors and Affiliations

  1. Department of Biotechnology and Informatics, BUITEMS, Quetta, Pakistan

    Rashida Hussain, Naseebullah Kakar, Abdul Hameed Baloch, Muhammad Azam Kakar & Jamil Ahmad

  2. Sardar Bahadur Khan Women University, Brewery Road, Quetta, Pakistan

    Rashida Hussain

  3. Centre for Applied Molecular Biology (CAMB), Lahore, Pakistan

    Shakeela Daud

  4. Institute of Biochemistry and Biotechnology, UVAS, Lahore, Pakistan

    Shakeela Daud

  5. Mayo Hospital, Lahore, Pakistan

    Adeel Ahmad

  6. University of the Balochistan, Quetta, Pakistan

    Abdul Malik Tareen

Authors
  1. Rashida Hussain
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  2. Shakeela Daud
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  3. Naseebullah Kakar
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  4. Adeel Ahmad
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  5. Abdul Hameed Baloch
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  6. Abdul Malik Tareen
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  7. Muhammad Azam Kakar
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  8. Jamil Ahmad
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Corresponding author

Correspondence to Jamil Ahmad.

Additional information

Rashida Hussain and Shakeela Daud have contributed equally to this study.

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Hussain, R., Daud, S., Kakar, N. et al. A missense mutation (p.G274R) in gene ASPA causes Canavan disease in a Pakistani family. Mol Biol Rep 39, 6197–6201 (2012). https://doi.org/10.1007/s11033-011-1438-2

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  • DOI: https://doi.org/10.1007/s11033-011-1438-2

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