Mutation analysis of ASPM gene in two Pakistani Famillies with autosomal recessive primary microcephaly

Paper Details

Research Paper 01/03/2019
Views (221) Download (9)
current_issue_feature_image
publication_file

Mutation analysis of ASPM gene in two Pakistani Famillies with autosomal recessive primary microcephaly

Hina Mir, Abdul Haleem Shah, Ayesha Haleem Shah, Wasim Ahmad
Int. J. Biosci.14( 3), 488-492, March 2019.
Certificate: IJB 2019 [Generate Certificate]

Abstract

Autosomal recessive primary microcephaly (MCPH) is a disorder of fetal brain growth, with reduced head circumference. The affected individuals exhibit reduced occipital-frontal head circumference (>2 SD) and mild-to-severe mental retardation. Autosomal recessive primary microcephaly is genetically heterogeneous and 18 loci have been reported to date. Mutations in ASPM gene are the most common cause of MCPH in the majority of the cases. The objective of the study was to search for pathogenic mutations in two Pakistani families with autosomal recessive primary microcephaly. In the current investigation, we have identified a previously reported mutation in ASPM gene. DNA samples of all available affected and unaffected individuals were PCR amplified using microsatellite markers and further analyzed by DNA sequencing. DNA sequence analysis revealed a previously reported mutation (p.W1326*) in ASPM gene. This study furthur validate that mutations in ASPM are the major cause of autosomal recessive primary microcephaly in the Pakistani population.

VIEWS 10

Bond J, Roberts E, Mochida GH, Hampshire DJ, Scott S, Askham JM, Springell K, Mahadevan M, Crow YJ, Markham AF, Walsh CA, Woods CG. 2002. ASPM is a major determinant of cerebral cortical size. Nature Genetics 32, 316-320.

Fish JL, Kosodo Y, Enard W, Paabo S, Huttner WB. 2006. Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells. Proc Proceedings of the National Academy of Sciences USA 103, 10438-10443.

Mahmood S, Ahmad W, Hassan MJ. 2011. Autosomal recessive primary microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum. Orphanet Journal of Rare Diseases 39, 1172-1186.

Matise TC, Chen F, Chen W, De La Vega FM, Hansen M, He C, Hyland FC, Kennedy GC, Kong X, Murray SS, Ziegle JS, Stewart WC, Buyske S. 2007. A second-generation combined linkage physical map of the human genome. Genome Research 17, 1783-1786.

Mir H, Khan S, Arif MS, Ali G, Wali A, Ansar M, Ahmad W. 2012. Mutations in the gene phospholipase C, delta-1 (PLCD1) underlying hereditary leukonychia. European Journal of Dermatology 22, 736-739.

Nicholas AK, Swanson EA, Cox JJ, Karbani G, Malik S, Springell K, Hampshire D, Ahmed M, Bond J, Di Benedetto D, Fichera M, Romano C, Dobyns WB, Woods CG. 2009. The molecular landscape of ASPM mutations in primary microcephaly. Journa of Medical Genetics 46, 249-253.

Paramasivam M, Chang YJ, LoTurco JJ. 2007. ASPM and Citron Kinase Co-Localize to the Midbody Ring During Cytokinasis. Cell Cycle 6, 1605-1613.

Saunders RD, Avides MC, Howard T, Gonzalez C, Glover DM. 1997. The Drosophila gene abnormal spindle encodes a novel microtubule-associated protein that associates with the polar regions of the mitotic spindle. Journal of Cell Biology 137, 881-890.

Thornton GK, Woods CG. 2009. Primary microcephaly: do all roads lead to Rome? Trends in Genetics 25, 501-510.

Wang R, Khan A, Han S, Zhang X. 2017. Molecular analysis of 23 Pakistani families with autosomal recessive primary microcephaly using targeted next-generation sequencing Journal of Human Genetics 62, 299-304.

Zhong X, Liu L, Zhao A, Pfeifer GP, Xu X. 2005. The abnormal spindle-like, microcephaly-associated (ASPM) gene encodes a centrosomal protein. Cell Cycle 4, 1227-9.