Expanding the clinical phenotype of patients with a ZDHHC9 mutation.

In 2007, 250 families with X-linked intellectual disability (XLID) were screened for mutations in genes on the X-chromosome, and in 4 of these families, mutations in the ZDHHC9 gene were identified. The ID was either isolated or associated with a marfanoid habitus. ZDHHC9 encodes a palmitoyl transferase that catalyzes the posttranslational modification of NRAS and HRAS. Since this first description, no additional patient with a ZDHHC9 mutation has been reported in the literature. Here, we describe a large family in which we identified a novel pathogenic ZDHHC9 nonsense mutation (p.Arg298*) by parallel sequencing of all X-chromosome exons. The mutation cosegregated with the clinical phenotyp…

20 ans après: a second mutation in MAOA identified by targeted high-throughput sequencing in a family with altered behavior and cognition

Intellectual disability (ID) is characterized by an extraordinary genetic heterogeneity, with >250 genes that have been implicated in monogenic forms of ID. Because this complexity precluded systematic testing for mutations and because clinical features are often non-specific, for some of these genes only few cases or families have been unambiguously documented. It is the case of the X-linked gene encoding monoamine oxidase A (MAOA), for which only one nonsense mutation has been identified in Brunner syndrome, characterized in a single family by mild non-dysmorphic ID and impulsive, violent and aggressive behaviors. We have performed targeted high-throughput sequencing of 220 genes, includi…

A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability.

AbstractSemaphorins are a large family of secreted and membrane-associated proteins necessary for wiring of the brain. Semaphorin 5A (SEMA5A) acts as a bifunctional guidance cue, exerting both attractive and inhibitory effects on developing axons. Previous studies have suggested that SEMA5A could be a susceptibility gene for autism spectrum disorders (ASDs). We first identified a de novo translocation t(5;22)(p15.3;q11.21) in a patient with ASD and intellectual disability (ID). At the translocation breakpoint on chromosome 5, we observed a 861-kb deletion encompassing the end of the SEMA5A gene. We delineated the breakpoint by NGS and observed that no gene was disrupted on chromosome 22. We…

Brain Injured Patients versus Multiple Trauma Patients: Some Neurobehavioral and Psychopathological Aspects

BACKGROUND: The study aims to describe the neurobehavioral and psychopathological disorders in road crash victims with cerebral lesions compared with multiple trauma sufferers with no brain damage. METHODS: This study compares the neuropsychological and psychopathological developments of two groups of road crash victims (25 severe brain injuries (SBI) and 25 multiple traumas (MULT)) on the basis of the Neurobehavioral Scale, the SCL 90-R and the State/Trait Anxiety Scale. RESULTS: On the basis of the Neurobehavioral Scale, it was clear that the SBI patients suffered from significantly more disorders of type factor 1 (self-appraisal and flexible thinking), factor II (withdrawal), factor III …

Additional evidence to support the role of the 20q13.33 region in susceptibility to autism

Dans l’hépatite chronique C, les délais entre diagnostic et traitement sont liés à la relation médecins-patients

Une etude epidemiologique menee en 2004 en Cote d’Or et dans le Doubs revelait que parmi 1 251 patients porteurs du VHC, un sur 4 etait traite et un sur 6 ne beneficiait d’aucune prise en charge. Une etude qualitative faite en Bourgogne en 2006-2008 visait a identifier les raisons de l’insuffisance de soins ; 25 medecins ont ete interroges sur leur confrontation a l’infection par le VHC et les difficultes de sa prise en charge, et 27 patients atteints d’hepatite chronique C sur les circonstances du depistage et du diagnostic, l’itineraire de soins, la representation et le vecu de la maladie et du traitement, les relations avec les soignants. L’etude a revele une grande variabilite dans les …