Polymicrogyria (PMG) is a cortical brain malformation which is characterized by an excessive number of small irregular gyri separated by shallow sulci, which leads to an irregular cortical surface. PMG varies widely in extent and location in the brain depending on the underlying etiology or syndrome, and can be isolated to a single region of one hemisphere, bilateral and asymmetric, bilateral and symmetric, or diffuse. Depending on the extent, subtype, and underlying etiology of PMG, clinical manifestations may range from selective impairment of cognitive function to severe encephalopathy with intractable epilepsy. PMG may be isolated, or observed as part of a multiple congenital anomaly syndrome. It may be associated with a genetic etiology, or may be due to exogenic causes such as infection, or impaired hemodynamic disturbances. Our Polymicrogyria Panel includes full gene sequencing of GPR56, KIAA1279, OCLN, SRPX2, TUBA1A, TUBA8, TUBB2B and TUBB3.
This oligonucleotide microarray-based assay allows for the detection of exonic deletions or duplications of 105 genes currently tested in our laboratory. This is a custom designed array by Agilent technologies that contains ~140,000 probes present in a 4x180K format with probes more densely spaced in the exons of the genes being tested. The array has been designed to detect copy number changes as small as 300-400 bp. Single genes and custom panels of clinically related genes can be analyzed for deletions and duplications and results may be confirmed by qPCR, MLPA or alternative methodologies.
This assay will allow deletion/duplication analysis for disorders known to be caused by deletions or duplications within a single gene as well as for disorders for which the frequency of gene deletions/duplications is currently not well established. The array-CGH test is particularly indicated for disorders resulting from loss of function or haploinsufficiency. In addition, testing for exonic deletions/duplications is useful in autosomal recessive conditions in which only one mutation is identified by sequence analysis. This assay will detect exonic deletions/duplications of the 105 genes on the array that may not be detected by whole genome array CGH.
Bilateral frontoparietal polymicrogyria (BFPP) [OMIM #606854] is characterized by moderate-severe mental retardation, seizures, dysconjugate gaze, and characteristic radiological findings. Mutations of the GPR56 [OMIM #604110] gene, or G-protein coupled receptor 56, have been identified in patients with BFPP. Piao X, et al [2005] studied patients with BFPP along with some patients with other polymicrogyria syndromes. All 29 patients with BFPP were found to be homozygous for GPR56 mutations. However, no patients without the BFPP cortical distribution or without both white matter and posterior fossa changes were found to mutations in GPR56. Deletions and/or duplications of the GPR56 gene as causative of disease have been reported.
Bilateral frontoparietal polymicrogyria (BFPP) [OMIM #606854] is characterized by moderate-severe mental retardation, seizures, dysconjugate gaze, and characteristic radiological findings. Mutations of the GPR56 [OMIM #604110] gene, or G-protein coupled receptor 56, have been identified in patients with BFPP. Piao X, et al [2005] studied patients with BFPP along with some patients with other polymicrogyria syndromes. All 29 patients with BFPP were found to be homozygous for GPR56 mutations. However, no patients without the BFPP cortical distribution or without both white matter and posterior fossa changes were found to mutations in GPR56. Sequencing of GPR56 can be ordered as a single test, or as part of our Polymicrogyria Panel.
