Association of Y Chromosome Haplotypes With Autism

Serajee, Fatema J.; Huq, A.H.M. Mahbubul

doi:10.1177/0883073809333530

Cited by 29 publications

(24 citation statements)

References 19 publications

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“…There has been limited ASD research on Y-chromosome specific genes. Polymorphisms in the neuroligin 4Y ( NLGN4Y ) gene involved in neurodevelopment and synaptic function have been associated with ASD [47, 48], and Ross et al recently published genetic data demonstrating a positive correlation between NLGN4Y expression and ASD symptoms in children with XYY [49]. …”

Section: Discussionmentioning

confidence: 99%

Autism Spectrum Disorder in Males with Sex Chromosome Aneuploidy: XXY/Klinefelter Syndrome, XYY, and XXYY

Tartaglia

Wilson

Miller

et al. 2017

J Dev Behav Pediatr

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Objective Neurodevelopmental concerns in males with sex chromosome aneuploidy (SCA) (XXY/Klinefelter syndrome, XYY, and XXYY) include many symptoms seen in autism spectrum disorder (ASD), such as speech-language impairment, verbal cognitive deficits, and social difficulties. Studies using standardized ASD assessment measures in SCA are few, and rates of ASD diagnosis in SCA using DSM-5 criteria for ASD have not been explored. We aimed to: (1) evaluate ASD characteristics in research cohorts of males with SCA using standardized assessments under DSM-IV compared to DSM-5 criteria, and (2) analyze whether type of SCA, prenatal vs. postnatal diagnosis, cognitive abilities, adaptive functioning, and socioeconomic status are associated with ASD diagnosis. Methods Participants from two sites with XXY/KS (n=20), XYY (n=57) and XXYY (n=21) were evaluated using protocols including medical history, cognitive testing, adaptive functioning, the Social Communication Questionnaire, Social Responsiveness Scale, Autism Diagnostic Observations Schedule (ADOS), the Autism Diagnostic Interview-Revised (ADI-R), and DSM criteria for ASD. Clinical impressions of ASD diagnostic category using the ADOS and DSM-IV criteria were compared to the ADOS-2 and DSM-5 criteria. T-tests were used to compare cognitive, adaptive, SES and prenatal vs. postnatal diagnoses between ASD versus no ASD groups determined by DSM-5 criteria. Results ASD rates in these research cohorts using DSM-IV criteria were 5% in XXY/KS, 33% in XYY, and 43% in XXYY. Rates of 10% in XXY/KS, 38% in XYY, and 52% in XXYY using ADOS-2 and DSM-5 criteria were not statistically higher. In both XYY and XXYY, the ASD group had lower verbal IQ and adaptive functioning compared to the group without ASD. Many children with SCA who did not meet full ASD criteria showed some deficits in social communication or social interaction skills. Conclusion The rate of ASD in children with SCA in this study was higher than expected compared to the general population. Males with Y chromosome aneuploidy (XYY and XXYY) were 4.8 times more likely to have a diagnosis of ASD than the XXY/KS group, and 20 times more likely than males in the general population based on the 2010 Centers for Disease Control (CDC) estimate of 1 in 42 males. ASD is an important consideration when evaluating social difficulties for children with SCA. Studies of males with SCA and Y-chromosome genes may provide insight into idiopathic ASD and male predominance in ASD.

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Section: Discussionmentioning

confidence: 99%

Autism Spectrum Disorder in Males with Sex Chromosome Aneuploidy: XXY/Klinefelter Syndrome, XYY, and XXYY

Tartaglia

Wilson

Miller

et al. 2017

J Dev Behav Pediatr

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“…One group found no differences in Y haplotype distribution between individuals with ASD and controls [64]. Another group found some Y haplotypes that were more or less common in ASD individuals compared to a nonaffected population [65]. Thus a significant contribution of sex chromosomes in the etiology of the majority of cases of ASD seems unlikely but warrants further research.…”

Section: Sex Chromosome Theory: Is XX Protective or Is Xy A Risk Factor?mentioning

confidence: 99%

Sex Differences in Autism Spectrum Disorder: a Review

Ferri

Brodkin

2018

Curr Psychiatry Rep

283

181

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Recent work on the biological basis of the male preponderance of autism and other neurodevelopmental disorders includes discussion of a higher genetic burden in females and sex-specific gene mutations or epigenetic changes that differentially confer risk to males or protection to females. Other mechanisms discussed are sex chromosome and sex hormone involvement. Specifically, fetal testosterone is involved in many aspects of development and may interact with neurotransmitter, neuropeptide, or immune pathways to contribute to male vulnerability. Finally, the possibilities of female underdiagnosis and a multi-hit hypothesis are discussed. This review highlights current theories of male bias in developmental disorders. Topics include environmental, genetic, and epigenetic mechanisms; theories of sex chromosomes, hormones, neuroendocrine, and immune function; underdiagnosis of females; and a multi-hit hypothesis.

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“…Comparison of Y chromosome haplotype groups between cases and controls represents an alternative strategy to identifying Y chromosome effects. Two such studies have been conducted in regard to ASC—one was positive [98] and one was negative [99]. Y chromosome effects certainly merit additional research attention, but current evidence is too sparse to evaluate to what extent this mechanism could explain the sex bias in ASC.…”

Section: What Might Cause An Extreme Male Brain?mentioning

confidence: 99%

Why Are Autism Spectrum Conditions More Prevalent in Males?

et al. 2011

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Autism Spectrum Conditions (ASC) are much more common in males, a bias that may offer clues to the etiology of this condition. Although the cause of this bias remains a mystery, we argue that it occurs because ASC is an extreme manifestation of the male brain. The extreme male brain (EMB) theory, first proposed in 1997, is an extension of the Empathizing-Systemizing (E-S) theory of typical sex differences that proposes that females on average have a stronger drive to empathize while males on average have a stronger drive to systemize. In this first major update since 2005, we describe some of the evidence relating to the EMB theory of ASC and consider how typical sex differences in brain structure may be relevant to ASC. One possible biological mechanism to account for the male bias is the effect of fetal testosterone (fT). We also consider alternative biological theories, the X and Y chromosome theories, and the reduced autosomal penetrance theory. None of these theories has yet been fully confirmed or refuted, though the weight of evidence in favor of the fT theory is growing from converging sources (longitudinal amniocentesis studies from pregnancy to age 10 years old, current hormone studies, and genetic association studies of SNPs in the sex steroid pathways). Ultimately, as these theories are not mutually exclusive and ASC is multi-factorial, they may help explain the male prevalence of ASC.

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Association of Y Chromosome Haplotypes With Autism

Cited by 29 publications

References 19 publications

Autism Spectrum Disorder in Males with Sex Chromosome Aneuploidy: XXY/Klinefelter Syndrome, XYY, and XXYY

Autism Spectrum Disorder in Males with Sex Chromosome Aneuploidy: XXY/Klinefelter Syndrome, XYY, and XXYY

Sex Differences in Autism Spectrum Disorder: a Review

Why Are Autism Spectrum Conditions More Prevalent in Males?

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