Disease Gene Discovery for Microcephaly in Consanguineous Pakistani Families

Abstract

Microcephaly is a genetic condition where the brain does not develop normally resulting in a reduced head circumference, and the disorder can be non-syndromicor syndromic.There are two types of microcephaly: primaryand secondary. Microcephaly is passed down through family lines as an X-linked recessive autosomal dominant or recessive disorder.Microcephaly can be segregated in families through consanguineous marriages. These interfamilial marriages can lead to the child inheriting identical defective copies of genes from both parents, which results in an autosomal recessive disease.This paper will explore four Pakistani families, each practicing consanguineous marriages that have resulted in individuals displaying syndromic and non-syndromic microcephaly.A list of chromosomal regions obtained from genotyping methods allowed for the narrowing down of potential causative genes in each family. Using online search engines, including Endeavour and the Human Genome Browser, four lists of candidate genes were obtained, one for each family.For two families, a defect in the ASPMgene, a gene that is reported to cause primary microcephaly,has beendiscovered. Potential candidate genes, including SCN7AandPKIB, present in chromosomal regions found through homozygosity mapping of the remaining two families could be the cause of the phenotype and will be discussed.