A Child with a Novel de novo Mutation in the Aristaless Domain of the Aristaless-Related Homeobox &lt;b&gt;&lt;i&gt;(ARX)&lt;/i&gt;&lt;/b&gt; Gene Presenting with Ambiguous Genitalia and Psychomotor Delay

Sirisena, Nirmala D.; McElreavey, Kenneth; Bashamboo, Anu; Silva, K. Shamya H. de; Jayasekara, Rohan W.; Dissanayake, Vajira H W

doi:10.1159/000365458

Cited by 11 publications

(10 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Exome sequencing is expanding the phenotypic spectrum associated with mutations in genes known to be associated with DSD. This has included mutations in the FGFR1, LHCGR, DHH, ARX genes (59)(60)(61)(62). NGS is becoming a diagnostic tool in DSD.…”

Section: New Approaches To Understand the Genetics Of Human Sdmentioning

confidence: 99%

Anomalies in human sex determination provide unique insights into the complex genetic interactions of early gonad development

et al. 2017

View full text Add to dashboard Cite

Human sex determination (SD) involves complex mutually antagonistic genetic interactions of testis‐ and ovary‐determining pathways. For many years, both male and female SD were considered to be regulated by a linear cascade of pro‐male and pro‐female genes, respectively; however, it has become clear that male and female development is achieved through the repression of the alternative state. A gene determining the formation of a testis may function by repressing the female state and vice versa. Uniquely in development, SD is achieved by suppression of the alternate fate and maintained in adulthood by a mutually antagonistic double‐repressive pathway. Here, we review genetic data generated through large‐scale sequencing approaches that are changing our view of how this system works, including the recently described recurrent NR5A1 p.R92W mutation associated with testis development in 46,XX children. We also review some of the unique challenges in the field to establish that mutations, such as this are pathogenic. The impending surge of new genetic data on human SD from sequencing projects will create opportunities for the development of mechanistic models that will clarify how the system operates and importantly provide data to understand how selection and developmental processes interact to direct the evolution of SD across species.

show abstract

Section: New Approaches To Understand the Genetics Of Human Sdmentioning

confidence: 99%

Anomalies in human sex determination provide unique insights into the complex genetic interactions of early gonad development

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In humans, mutations in ARX have been reported in patients with Xlinked lissencephaly and ambiguous genitalia (XLAG) syndrome (Kitamura et al, 2002). Recently, a de novo missense mutation in ARX has been shown to cause ambiguous genitalia associated with psychomotor delay in the absence of characteristic features of the XLAG syndrome such as lissencephaly, agenesis of the corpus callosum or intractable epilepsy (Sirisena et al, 2014).…”

Section: Arxmentioning

confidence: 99%

Why boys will be boys and girls will be girls: Human sex development and its defects

Eid

Biason‐Lauber

2016

Birth Defects Research Pt C

View full text Add to dashboard Cite

Among the most defining events of an individual's life, is the development of a human embryo into male or a female. The phenotypic sex of an individual depends on the type of gonad that develops in the embryo, a process which itself is determined by the genetic setting of the individual. The development of the gonads is different from any other organ, as they possess the potential to differentiate into two functionally distinct organs, testes, or ovaries. Sex development can be divided into two distinctive processes, “sex determination,” which is the commitment of the undifferentiated gonad into either a testis or an ovary, a process that is genetically programmed in a critically timed manner and “sex differentiation,” which takes place through hormones produced by the gonads, once the developmental sex determination decision has been made. Disruption of any of the genes involved in either the testicular or ovarian development pathway could lead to disorders of sex development. In this review, we provide an insight into the factors important for sex determination, their antagonistic actions and whenever possible, references on the “prismatic” clinical cases are given. Birth Defects Research (Part C) 108:365–379, 2016. © 2016 Wiley Periodicals, Inc.

show abstract

“…Postnatally, instead, it is mostly expressed in GABAergic neurons in the cortex and basal ganglia. [2][3][4][5][6][7][8][9][10][11][12][13][14] Genetics ARX is a homeobox transcription factor that spans a 12.24 kb genomic region at the short arm of the X chromosome (Xp21.3, MIM 300382). It comprises five exons that encode for a 562amminoacids protein.…”

Section: Introductionmentioning

confidence: 99%

Aristaless-Related Homeobox (ARX): Epilepsy Phenotypes beyond Lissencephaly and Brain Malformations

Scalia

Venti

Ciccia

et al. 2021

Journal of Pediatric Neurology

View full text Add to dashboard Cite

The Aristaless-related homeobox (ARX) transcription factor is involved in the development of GABAergic and cholinergic neurons in the forebrain. ARX mutations have been associated with a wide spectrum of neurodevelopmental disorders in humans and are responsible for both malformation (in particular lissencephaly) and nonmalformation complex phenotypes. The epilepsy phenotypes related to ARX mutations are West syndrome and X-linked infantile spasms, X-linked myoclonic epilepsy with spasticity and intellectual development and Ohtahara and early infantile epileptic encephalopathy syndrome, which are related in most of the cases to intellectual disability and are often drug resistant. In this article, we shortly reviewed current knowledge of the function of ARX with a particular attention on its consequences in the development of epilepsy during early childhood.

show abstract

A Child with a Novel de novo Mutation in the Aristaless Domain of the Aristaless-Related Homeobox <b><i>(ARX)</i></b> Gene Presenting with Ambiguous Genitalia and Psychomotor Delay

Cited by 11 publications

References 11 publications

Anomalies in human sex determination provide unique insights into the complex genetic interactions of early gonad development

Anomalies in human sex determination provide unique insights into the complex genetic interactions of early gonad development

Why boys will be boys and girls will be girls: Human sex development and its defects

Aristaless-Related Homeobox (ARX): Epilepsy Phenotypes beyond Lissencephaly and Brain Malformations

Contact Info

Product

Resources

About