BACKGROUND-Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients.

This study describes three boys carrying CDKL5 missense mutations and their detailed clinical and EEG data, and indicates that CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. Screening for CDKL5 mutations is strongly recommended in individuals with these clinical features.

Hereditary spastic paraplegias (HSPs) are characterized by progressive lower extremity spasticity due to an axonal degeneration of motor and sensory neurons. We report a four-generation pedigree segregating an autosomal dominant phenotype for HSP and showing a linkage to the SPG10 locus, coding for Kinesin family member 5A. Subsequent to a denaturing high performance liquid chromatography (dHPLC) mutation screening we found a new missense mutation 838C>T (R280C) at an invariant arginine residue in a region involved in the microtubule binding activity.

Background: To our knowledge, up to now, only 2 mutations in the KIF5A gene, a member of the kinesin superfamily, have been identified as the molecular cause of early-onset autosomal dominant hereditary spastic paraparesis (ADHSP). Objective: To assess the genetic defect in a family with late-onset ADHSP. Patients and Methods: Only the proband agreed to undergo complete neurological testing and mutational analysis. The proband was screened for mutations in the spastin, atlastin, NIPA1, and KIF5A genes, either by denaturing high-performance liquid chromatography or sequence analysis. Results: The history of the family was consistent with ADHSP characterized by late onset of the disease. Mutational analysis results were negative for the spastin, atlastin, and NIPA1 genes but identified a missense mutation (c.1082CϾT) in the coiled-coil coding region of the KIF5A gene. Conclusions: This finding enlarges the phenotypic spectrum of ADHSP linked to KIF5A and enhances the role of that gene in the epidemiology of this disease. We propose that the KIF5A gene should be routinely analyzed in patients with hereditary spastic paraplegia negative for spastin and atlastin mutations.

BackgroundThe interstitial 6p deletions, involving the 6p22-p24 chromosomal region, are rare events characterized by variable phenotypes and no clear genotype-phenotype correlation has been established so far.ResultsHigh resolution array-CGH identified 1 Mb de novo interstitial deletion in 6p22.3 chromosomal region in a patient affected by severe Intellectual Disability (ID), Autism Spectrum Disorders (ASDs), and electroencephalographic anomalies. This deletion includes ATXN1, DTNBP1, JARID2 and MYLIP genes, known to play an important role in the brain, and the GMPR gene whose function in the nervous system is unknown.ConclusionsWe support the suggestion that ATXN1, DTNBP1, JARID2 and MYLIP are candidate genes for the pathophysiology of ASDs and ID, and we propose that deletion of DTNBP1 and/or JARID2 contributes to the hypotonia phenotype.