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Molecular Biology Reports

, Volume 39, Issue 5, pp 6197–6201 | Cite as

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

  • Rashida Hussain
  • Shakeela Daud
  • Naseebullah Kakar
  • Adeel Ahmad
  • Abdul Hameed Baloch
  • Abdul Malik Tareen
  • Muhammad Azam Kakar
  • Jamil Ahmad
Article

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.

Keywords

Canavan disease ASPA gene Pakistani family ASPA mutation 

Notes

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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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Rashida Hussain
    • 1
    • 2
  • Shakeela Daud
    • 3
    • 4
  • Naseebullah Kakar
    • 1
  • Adeel Ahmad
    • 5
  • Abdul Hameed Baloch
    • 1
  • Abdul Malik Tareen
    • 6
  • Muhammad Azam Kakar
    • 1
  • Jamil Ahmad
    • 1
  1. 1.Department of Biotechnology and InformaticsBUITEMSQuettaPakistan
  2. 2.Sardar Bahadur Khan Women UniversityQuettaPakistan
  3. 3.Centre for Applied Molecular Biology (CAMB)LahorePakistan
  4. 4.Institute of Biochemistry and BiotechnologyUVASLahorePakistan
  5. 5.Mayo HospitalLahorePakistan
  6. 6.University of the BalochistanQuettaPakistan

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