Autistic behavior in children with fragile X syndrome: Prevalence, stability, and the impact of FMRP

Hatton, Deborah D.; Sideris, John; Skinner, Martie L.; Mankowski, Jean Boswell; Bailey, Donald B.; Roberts, Jane; Mirrett, Penny

doi:10.1002/ajmg.a.31286

Cited by 335 publications

(302 citation statements)

References 44 publications

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“…Approximately 20% of boys with fragile X syndrome meet diagnostic criteria for ASDs when evaluated by objective criteria. 11,47 Two early studies found an incidence of abnormal fragile X studies of 6% in unselected cohorts of boys with ASDs. These studies noted 4 of 75 (5.3%) 48 and 17 of 210 (8%) 49 positive rates.…”

Section: Single-gene Disordersmentioning

confidence: 99%

Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions

Schaefer

Mendelsohn

2013

Genetics in Medicine

439

393

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Autism spectrum disorders (ASDs), also known as pervasive developmental disorders, are a behaviorally defined group of neurodevelopmental disorders that are usually diagnosed in early childhood. They are characterized by varying degrees of limitations in communication and social interaction and by atypical, repetitive behaviors with an onset before 3 years of age. The phenotype of ASDs is extremely heterogeneous, with differences from person to person in a wide range of symptoms and severity as well as differences between the various subtypes of ASDs (e.g., autistic disorder, Asperger syndrome, and pervasive developmental disorder not otherwise specified).Multiple lines of epidemiologic evidence support the strong role of genetics in the etiology of ASDs. 1-3 Results of population studies of unselected cases of autism are most consistent with multifactorial inheritance. Until quite recently, the accepted recurrence risk for full siblings of a child with autism has been in the range of 3-10%. [4][5][6] Overall, only 2-3% of families have more than one affected child (possibly because of voluntary avoidance of pregnancy after a child is diagnosed). Most studies have reported a sex bias in the recurrence risk in keeping with the presumption of a "multifactorial" mode of inheritance (higher risk if the affected person is of the less commonly affected sex). As such, the reported risk is 7% of another affected child if the first affected child is female and 4% if the first affected child is male. 7 If multiple children (two or more) have autism, the recurrence risk is on the order of 33-50% for any future pregnancy. 7 Two recent studies 8,9 have reported even higher recurrence risks of 11 and 19% with single-sibling involvement. The first 8 was a retrospective self-enrolled/self-identified study using an interactive website. The diagnosis was confirmed, but the identification of second siblings may be a source of ascertainment bias. The second 9 was an international multisite prospective study in 664 families with a calculated 19% recurrence risk. Interestingly, the typically reported sex bias was not noted in one of these studies. 8 Both were single studies that bear replication.The autism spectrum disorders are a collective of conditions that have in common impaired socialization and communication in association with stereotypic behaviors. The reported incidence of autism spectrum disorders has increased dramatically over the past two decades. In addition, increased attention has been paid to these conditions by both lay and professional groups. These trends have resulted in an increase in the number of referrals to clinical geneticist for the evaluation of persons with autism spectrum disorders. The primary roles of the geneticist in this process are to define etiology when possible, to provide genetic counseling, and to contribute to case management. In deciding on the appropriate evaluation for a particular patient, the geneticist will consider a host of factors: (i) ensuring an accurate diagnosis of autism befor...

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Section: Single-gene Disordersmentioning

confidence: 99%

Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions

Schaefer

Mendelsohn

2013

Genetics in Medicine

439

393

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“…FXS is a frequent monogenic cause of ASD 74,[76][77][78] and the behavioral overlap between autism and FXS patients suggests overlapping neuronal network mechanisms that increase susceptibility to ASD. The regulatory function of CYFIP1 in the context of FMRP-and WAVE-containing complexes and subsequent actin remodeling may explain the convergence of these two neurodevelopmental disorders.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…[1][2][3][4][5] FXS is caused by a full mutation, an expansion of CGG trinucleotide repeats (4200 CGG repeats) in the 5'UTR of the FMR1 gene. Individuals harboring an allele with 55-200 CGG repeats are premutation carriers.…”

Section: Introductionmentioning

confidence: 99%

De novo microduplication of the FMR1 gene in a patient with developmental delay, epilepsy and hyperactivity

et al. 2012

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Loss-of-function due to expansion of a CGG repeat located in the 5'UTR of the FMR1 gene is the most frequent cause of fragile X syndrome. Less than 1% of individuals with fragile X syndrome have been reported to have a partial or full deletion or point mutation of the FMR1 gene. However, whether a copy number gain of the FMR1 gene could result in certain clinical phenotypes has not been fully investigated. Here, we report the case of a child who presented with developmental delay starting at 9 months of age, fine motor and speech delay, progressive seizures since 18 months of age and hyperactivity. Molecular workup identified a de novo microduplication in the Xq27.3 region, including the FMR1 gene and the ASFMR1 gene. The expression level of the FMR1 gene in peripheral blood did not differ from that of the controls. In addition, an inherited 363-kb duplication on the chromosome 1q44 region and an inherited deletion of 168 kb on the chromosome 4p15.31 region were detected. It is not clear whether these inherited copy number variations (CNVs) also have a modifying role in the clinical phenotype of this patient.

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Autistic behavior in children with fragile X syndrome: Prevalence, stability, and the impact of FMRP

Cited by 335 publications

References 44 publications

Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions

Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions

Dendritic spine actin cytoskeleton in autism spectrum disorder

De novo microduplication of the FMR1 gene in a patient with developmental delay, epilepsy and hyperactivity

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