Date of Award


Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Murat Gunel


This study utilized novel genetic techniques in order to find causative gene mutations that underlie diseases of neural development. Our laboratory has collected 175 cases of malformations of cortical development (MCD) from the United States and Europe. Four of these cases are the focus of this manuscript: two familial cases of infantile neuroaxonal dystrophy (INAD), a familial case of hereditary spastic paraparesis (HSP), and a sporadic case of Greig cephalopolysyndactyly (GCPS) and cerebral cavernous malformations (CCMs). The techniques utilized to study the affected patients include microarray-based single nucleotide polymorphism (SNP) genotyping and copy number variation (CNV) analysis, both of which are powerful tools in the hunt for disease-causing gene mutations. In the familial cases of INAD, we report two novel mutations in the PLA2G6 gene, previously shown to cause INAD when mutated. In the familial case of HSP, we demonstrate linkage to the SPG11 locus on chromosome 15q. Finally, in the sporadic case of GCPS and CCM, we published the first report on this novel syndrome along with a genetic analysis that demonstrates a microdeletion on chromosome 7p, resulting in heterozygous loss of both the GLI3 and CCM2 genes. The three studies presented in this manuscript demonstrate the utility of SNP genotyping and CNV analysis in revealing the genetic mutations that underlie diseases of neural development.

Open Access

This Article is Open Access