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Sex-linked Disorders01:43

Sex-linked Disorders

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Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
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Neurulation01:30

Neurulation

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Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the...
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X-linked Traits01:19

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In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
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Related Experiment Video

Updated: Dec 10, 2025

Osmotic Avoidance in Caenorhabditis elegans: Synaptic Function of Two Genes, Orthologues of Human NRXN1 and NLGN1, as Candidates for Autism
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Neuroligins and Neurodevelopmental Disorders: X-Linked Genetics.

Thien A Nguyen1,2, Alexander W Lehr1, Katherine W Roche1

  • 1Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.

Frontiers in Synaptic Neuroscience
|August 28, 2020
PubMed
Summary

Sex-linked neuroligin genes NLGN3 and NLGN4 on the X chromosome are strongly associated with autism spectrum disorder (ASD) and intellectual disability (ID). Research is exploring their synaptic function for better understanding neurodevelopmental disorders.

Keywords:
NLGN3NLGN4Xautismintellectual disabililtiesneuroligin

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Area of Science:

  • Neurogenetics
  • Developmental Neuroscience

Background:

  • Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social-communication deficits and restricted, repetitive behaviors, with a higher prevalence in males.
  • While autosomal genes are often studied, sex-linked genes, particularly on the X chromosome, encode crucial synaptic proteins implicated in ASD.
  • The neuroligin (NLGN) family of postsynaptic adhesion molecules includes sex-linked genes NLGN3 and NLGN4, which have been linked to ASD and intellectual disability (ID).

Purpose of the Study:

  • To review recent findings on the function of NLGN3 and NLGN4 isoforms at the synapse.
  • To highlight the role of sex-linked neuroligin genes in neurodevelopmental disorders like ASD and ID.
  • To discuss future research directions for understanding the synaptic mechanisms underlying ASD/ID.

Main Methods:

  • Review of existing literature on neuroligin gene function in ASD and ID.
  • Analysis of findings from rodent models and human-derived differentiated neurons.
  • Examination of the role of X-linked (NLGN3, NLGN4) and Y-linked (NLGN4Y) neuroligin isoforms.

Main Results:

  • NLGN3 and NLGN4 are identified as strong candidate genes for ASD and ID, located on the X chromosome.
  • These neuroligin isoforms play significant roles in synaptic function.
  • NLGN4Y, a Y-linked neuroligin, forms a pair with NLGN4X, suggesting complex sex-chromosome involvement.

Conclusions:

  • Sex-linked neuroligin genes NLGN3 and NLGN4 are critical candidates for understanding ASD and ID etiology.
  • Further research into the synaptic functions of these neuroligins in various models is essential.
  • Investigating X-Y neuroligin pairs may offer new insights into sex-biased prevalence in neurodevelopmental disorders.