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Classical lissencephaly (LIS) is a neuronal migration disorder resulting in brain malformation, epilepsy and mental retardation. Deletions or mutations of LIS1 on 17p13.3 and mutations in XLIS ( DCX ) on Xq22.3-q23 produce LIS. Direct DNA sequencing of LIS1 and XLIS was performed in 25 children with sporadic LIS and no deletion of LIS1 by fluorescence in(More)
Subcortical band heterotopia (SBH) are bilateral and symmetric ribbons of gray matter found in the central white matter between the cortex and the ventricular surface, which comprises the less severe end of the lissencephaly (agyria-pachygyria-band) spectrum of malformations. Mutations in DCX (also known as XLIS ) have previously been described in females(More)
Mutations in the CDKL5 gene (also known as STK9) have recently been shown to cause early onset epilepsy and severe mental retardation (ISSX or West syndrome). Patients with CDKL5 mutations sometimes also show features similar to those seen in Rett Syndrome (RTT). We have screened the CDKL5 gene in 94 patients with RTT or a RTT-like phenotype who had tested(More)
We previously showed that mutations in LIS1 and DCX account for approximately 85% of patients with the classic form of lissencephaly (LIS). Some rare forms of LIS are associated with a disproportionately small cerebellum, referred to as lissencephaly with cerebellar hypoplasia (LCH). Tubulin alpha1A (TUBA1A), encoding a critical structural subunit of(More)
BACKGROUND Classical lissencephaly or "smooth brain" is a human brain malformation that consists of diffuse agyria and pachygyria. Two genes associated with classical lissencephaly have recently been cloned-LIS1 from chromosome 17p13.3 and XLIS (also called DCX) from Xq22.3-q23. OBJECTIVE We performed genotype-phenotype analysis in children with(More)
Analysis of patients with inherited hypokalaemic alkalosis resulting from salt-wasting has proved fertile ground for identification of essential elements of renal salt homeostasis and blood-pressure regulation. We now demonstrate linkage of this phenotype to a segment of chromosome 1 containing the gene encoding a renal chloride channel, CLCNKB. Examination(More)
Several brain malformations have been described in rare patients with the deletion 22q11.2 syndrome (DEL22q11) including agenesis of the corpus callosum, pachygyria or polymicrogyria (PMG), cerebellar anomalies and meningomyelocele, with PMG reported most frequently. In view of our interest in the causes of PMG, we reviewed clinical data including(More)
The critical importance of cytoskeletal function for correct neuronal migration during development of the cerebral cortex has been underscored by the identities of germline mutations underlying a number of human neurodevelopmental disorders. The proteins affected include TUBA1A, a major alpha-tubulin isoform, and microtubule-associated components such as(More)
Deletions of 17p13.3, including the LIS1 gene, result in the brain malformation lissencephaly, which is characterized by reduced gyration and cortical thickening; however, the phenotype can vary from isolated lissencephaly sequence (ILS) to Miller-Dieker syndrome (MDS). At the clinical level, these two phenotypes can be differentiated by the presence of(More)
Lissencephaly is a cortical malformation secondary to impaired neuronal migration resulting in mental retardation, epilepsy and motor impairment. It shows a severity spectrum from agyria with a severely thickened cortex to posterior band heterotopia only. The LIS1 gene on 17p13.3 encodes a 45 kDa protein named PAFAH1B1 containing seven WD40 repeats. This(More)