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Background: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability (ID), as well as the most frequent monogenic cause of autism spectrum disorder (ASD). Men with FXS exhibit ID, often associated with autistics features, whereas women heterozygous for the full mutation are typically less severely affected; about half have a normal or borderline intelligence quotient (IQ). Previous findings have shown a strong association between ID and ASD in both men and women with FXS. We describe here the case of two sisters with ASD and FXS but without ID. One of the sisters presented with high-functioning autism, the other one with pervasive developmental disorder not otherwise specified and low normal IQ.
Methods: The methylation status of the mutated FMR1 alleles was examined by Southern blot and methylation-sensitive polymerase chain reaction. The X-chromosome inactivation was determined by analyzing the methylation status of the androgen receptor at Xq12.
Results: Both sisters carried a full mutation in the FMR1 gene, with complete methylation and random X chromosome inactivation. We present the phenotype of the two sisters and other family members.
Conclusions: These findings suggest that autistic behaviors and cognitive impairment can manifest as independent traits in FXS. Mutations in FMR1, known to cause syndromic autism, may also contribute to the etiology of high-functioning, non-syndromic ASD, particularly in women. Thus, screening for FXS in patients with ASD should not be limited to those with comorbid ID.
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http://dx.doi.org/10.1186/2040-2392-3-5 | DOI Listing |
Am J Hum Genet
November 2024
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; McLaughlin Centre, Toronto, ON M5G 0A4, Canada. Electronic address:
Autism spectrum disorder (ASD) exhibits an ∼4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males.
View Article and Find Full Text PDFCureus
November 2024
Dental Public Health, Kurdistan Higher Council of Medical Specialties, Erbil, IRQ.
Introduction Autism spectrum disorder (ASD) is a complicated disorder that affects communication, social interaction, and behavior. Several investigations have documented increased oxidative stress and damage in individuals with ASD compared with neurotypical controls. Saliva can be used as a non-invasive technique to assess oxidative stress biomarkers.
View Article and Find Full Text PDFJ Behav Ther Exp Psychiatry
March 2025
Department of Neuroscience, Imaging and Clinical Science, University "G. d'Annunzio" Chieti-Pescara, Via Luigi Polacchi, 11 66103 Chieti (CH), Italy.
Background And Objectives: Clinical practice reveals that individuals with autism characterized by the absence of cognitive impairment (High Functioning Autism-HFA) show difficulty in sharing attention with unfamiliar people. We hypothesized that this difficulty could affect cognitive control by selectively impairing stimulus-encoding or response-selection.
Methods: Twenty-one HFA and 23 neurotypical adults were involved in a two-phase study.
J Zhejiang Univ Sci B
November 2024
School of Population Medicine and Public Health, Chinese Academy of Medical Sciences / Peking Union Medical College, Beijing 100730, China.
The rising demand for child care is putting a strain on parents of children with autism spectrum disorder (ASD), particularly the mothers. This study investigated Chinese mothers of children with ASD and examined the factors associated with maternal mental health. An online national survey was completed by the parents of 5077 ASD children and adolescents aged 0‒17 years.
View Article and Find Full Text PDFBMC Med Genomics
November 2024
Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, 30625, Germany.
Background: MAGEL2 is an autism susceptibility gene whose deficiency has been associated with autism-related behaviors in animal models and in syndromic human autism spectrum disorders (ASDs) such as Schaaf-Yang syndrome, but has not been studied in the broader autism spectrum. Given the capabilities of long-read sequencing technologies, this pilot study used a targeted nanopore sequencing approach to simultaneously examine MAGEL2 DNA sequence and methylation in adults with high-functioning autism (HFA) compared to neurotypical controls (NC).
Methods: Using DNA extracted from peripheral blood, Cas9-targeted nanopore DNA sequencing was used to analyze MAGEL2, including its entire regulatory construct (chr15:23639316-23651466), for sequence variation and 5-methyl-cytosine (5mC) modification in a cohort of adults with HFA compared to sex- and age-matched NC.
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