Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome.

Fragile-X syndrome (FXS) is a frequent genetic form of intellectual disability (ID). The main recurrent mutagenic mechanism causing FXS is the expansion of a CGG repeat sequence in the 5'-UTR of the FMR1 gene, therefore, routinely tested in ID patients. We report here three FMR1 intragenic pathogenic variants not affecting this sequence, identified using high-throughput sequencing (HTS): a previously reported hemizygous deletion encompassing the last exon of FMR1, too small to be detected by array-CGH and inducing decreased expression of a truncated form of FMRP protein, in three brothers with ID (family 1) and two splice variants in boys with sporadic ID: a de novo variant c.

Transcranial Magnetic Stimulation Combined With Nicotine Replacement Therapy for Smoking Cessation: A Randomized Controlled Trial.

Background: Further evidence suggests that repetitive Transcranial Magnetic Stimulation (rTMS) is an effective method to reduce tobacco craving among smokers.

Hypothesis: As relapse is common within a few days after smoking cessation, we hypothesized that combining the anti-craving effects of rTMS with Nicotine replacement therapy (NRT) to attenuate withdrawal symptoms could increase abstinence rates in smokers with severe nicotine dependence who quit smoking.

Methods: Thirty-seven smokers who failed to quit with the usual treatments were randomly assigned to two treatment groups to receive either active (n = 18) or sham (n = 19) 1-Hz rTMS of the right dorsolateral prefrontal cortex.

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.

3q27.3 microdeletional syndrome: a recognisable clinical entity associating dysmorphic features, marfanoid habitus, intellectual disability and psychosis with mood disorder.

Background: Since the advent of array-CGH, numerous new microdeletional syndromes have been delineated while others remain to be described. Although 3q29 subtelomeric deletion is a well-described syndrome, there is no report on 3q interstitial deletions.

Methods: We report for the first time seven patients with interstitial deletions at the 3q27.