WITHDRAWN: Novel pathogenic mutation mapping of ASPM gene in consanguineous Pakistani families with primary microcephaly

Abstract

Abstract Background Primary microcephaly is a neurodevelopmental disorder characterized by congenital reduced 3 to 5 standard deviation of head circumference and non-progressive intellectual disability. The objective of the study was to search for pathogenic mutations, for awareness of etiology and understand the molecular mechanism of primary microcephaly. Methods Families affected with primary microcephaly are ascertained from different remote areas of Pakistan and collected their blood samples. DNA extraction was done by salting out method, quality and quantity of DNA were evaluated by spectrophotometer and 1% agarose gel electrophoresis. Mutation analysis were assessed by Whole exome sequencing and Sanger sequencing. Finding A novel 4-bp deletion mutation c.3877_3880delGAGA was detected in exon 17 of ASPM gene in two affected families (A and B), which result in frameshift mutation in ASPM gene followed truncate the protein synthesis (p. Glu1293Lysfs*10), loss of calmodulin-bimding IQ domain and Armadillo-like domain in Aspm protein. By using in silico tools like Mutation Taster, PROVEAN and Polyphen, Pathogenic effect of this novel mutation was tested and it was predicted as “disease causing” with high pathogenicity scores. Moreover, we also observed one previously reported mutation in exon 24 (c.9730C > T) of ASPM gene followed protein truncation (p. Arg1659*) in family C. Novelty Mutations in ASPM gene are the most common cause of MCPH in the majority of the cases. So, further affected families would be enrolled from remote areas of Pakistan that would helped out in identification or mapping of a novel mutations in ASPM gene.