We are offering three new brain malformation panels:
Our Polymicroygria panel is now available and include sequence analysis of six genes that have been associated with a polymicrogyria phenotype. 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. PMG may be isolated, or observed as part of a multiple congenital anomaly syndrome. The genes in this panel include GPR56, KIAA1279, OCLN, TUBA8, TUBB2B and TUBB3.
Our updated Cerebellar/Pontocerebellar Hypoplasia panel is now available and will include sequencing of 7 genes associated with cerebellar hypoplasia. Pontocerebellar hypoplasia (PCH) is a group of rare autosomal recessive neurodegenerative disorders with a prenatal onset, characterized by cerebellar hypoplasia in addition to varying degrees of atrophy of the cerebellum and pons. MRI findings include a small cerebellum and brainstem, variable neocortical atrophy, severe and progressive microcephaly and variable ventriculomegaly. Cerebellar vermis hypoplasia (CVH) consists of isolated vermis hypoplasia and may also be called “Dandy-Walker variant” due to the phenotypic overlap with Dandy-Walker malformation (DWM). DWM includes vermis hypoplasia in addition to several other features such as enlarged posterior fossa. The genes in this panel include CASK, OPHN1, RARS2, TSEN2, TSEN34, TSEN54 and VRK1.
Our Warburg Micro Syndrome panel will include sequencing of all three genes that have been associated with this syndrome to date: RAB3GAP1, RAB3GAP2 and RAB18. Warburg Micro syndrome is a rare autosomal recessive condition characterized by ocular and neurodevelopmental abnormalities and hypothalamic hypogonadism. Key clinical features include microphthalmia, microcornia, congenital cataracts, optic atrophy, microcephaly, cortical dysplasia and atrophy, congenital hypotonia, severe intellectual disability, and spastic diplegia. In addition to the characteristic ocular findings, common facial features include deep set eyes, wide nasal bridge and a narrow mouth. Brain magnetic resonance imaging (MRI) of affected individuals consistently shows polymicrogyria in the frontal and parietal lobes, wide sylvian fissures, thin corpus callosum and increased subdural spaces.
Comprehensive sequence coverage of the coding regions and splice junctions of all genes in these panels will be performed. Targets of interests will be amplified using highly parallelized and multiplexed PCR reactions assembled with the Raindance System. DNA will be sequenced using Illumina technology. Variants will be identified and evaluated using a custom collection of bioinformatic tools and comprehensively interpreted by our team of directors and genetic counselors. All novel and/or potentially pathogenic variants will be confirmed by Sanger sequencing. The technical sensitivity of this test is estimated to be >99% for single nucleotide changes and small insertions and deletions.
