Deletion in Xp22.11: PTCHD1 is a candidate gene for X-linked intellectual disability with or without autism

Filges, Isabel; Röthlisberger, Benno; Blattner, Ariane C.; Boesch, Nemya; Demougin, Philippe; Wenzel, Friedel; Huber, Ar R.; Heinimann, Karl; Weber, Peter; Miny, Peter

doi:10.1111/j.1399-0004.2010.01590.x

Cited by 49 publications

(44 citation statements)

References 24 publications

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“…Supporting this possibility, the Hh acyltransferase HHAT has been identified as mutated in whole-exon sequencing and proposed as a candidate gene for ID (Agha et al, 2014). Similarly, PTCHD1, which shares high homology with the Patched receptors, has been suggested as a candidate gene for ASD and ID (Noor et al, 2010;Filges et al, 2011;Chaudhry et al, 2015).…”

Section: Discussionmentioning

confidence: 86%

JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling

et al. 2017

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Components of the KDM7 family of histone demethylases are implicated in neuronal development and one member, PHF8, is often found to be mutated in cases of X-linked mental retardation. However, how PHF8 regulates neurodevelopmental processes and contributes to the disease is still largely unknown. Here, we show that the catalytic activity of a PHF8 homolog in Caenorhabditis elegans, JMJD-1.2, is required non-cell-autonomously for proper axon guidance. Loss of JMJD-1.2 dysregulates transcription of the Hedgehog-related genes wrt-8 and grl-16, the overexpression of which is sufficient to induce the axonal defects. Deficiency of either wrt-8 or grl-16, or reduced expression of homologs of genes promoting Hedgehog signaling, restores correct axon guidance in jmjd-1.2 mutants. Genetic and overexpression data indicate that Hedgehog-related genes act on axon guidance through actin remodelers. Thus, our study highlights a novel function of jmjd-1.2 in axon guidance that might be relevant for the onset of X-linked mental retardation and provides compelling evidence of a conserved function of the Hedgehog pathway in C. elegans axon migration.

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Section: Discussionmentioning

confidence: 86%

JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling

et al. 2017

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“…Among ASD cohorts, the 1q21.1 region is one often found to contain variants (MeVord et al 2008;Szatmari et al 2007), which may be either deletions or duplications, but there is some stratiWcation among the associated clinical features-most notably of micro-and macrocephaly with deletions and duplications, respectively (Brunetti-Pierri et al 2008). One striking recent Wnding is of mutations or deletions within and around the X-linked PTCHD1 gene in approximately 1% of individuals with ASD and/or intellectual disability (Filges et al 2011;Noor et al 2010;Pinto et al 2010). This will be signiWcant for translational applications, due to the numbers of carrier females who may be at risk to transmit these pathogenic variants.…”

Section: Introductionmentioning

confidence: 97%

Risk factors for autism: translating genomic discoveries into diagnostics

Scherer

Dawson

2011

Hum Genet

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Autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in communication and reciprocal social interaction, and the presence of restricted and repetitive behaviors. The spectrum of autistic features is variable, with severity of symptoms ranging from mild to severe, sometimes with poor clinical outcomes. Twin and family studies indicate a strong genetic basis for ASD susceptibility. Recent progress in defining rare highly penetrant mutations and copy number variations as ASD risk factors has prompted early uptake of these research findings into clinical diagnostics, with microarrays becoming a 'standard of care' test for any ASD diagnostic work-up. The ever-changing landscape of the generation of genomic data coupled with the vast heterogeneity in cause and expression of ASDs (further influenced by issues of penetrance, variable expressivity, multigenic inheritance and ascertainment) creates complexity that demands careful consideration of how to apply this knowledge. Here, we discuss the scientific, ethical, policy and communication aspects of translating the new discoveries into clinical and diagnostic tools for promoting the well-being of individuals and families with ASDs.

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“…Locus disruptions in the PTCHD1 gene have been associated with several forms of autism (Filges 2011;Noor 2010). Currently, several other genes are being researched, as the pathogenesis of autism likely involves the derailment of some of the processes of synaptic plasticity, maturation of neuron signaling, myelination, and neurite outgrowth during development.…”

Section: The Second Neurogenetic Phase: the Continuum Of Neuron-basedmentioning

confidence: 99%

The Neurogenetic Substructures of Human Consciousness

Grandy¹

2014

Essays Philos

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There are many interpretations of what consciousness is. In the past decade materialist and reductionist theories have gained in popularity as many neurological correlates of consciousness have been identified experimentally. This article presents a neurogenetic account of the underpinnings of neuron-based consciousness. In this paradigm, human consciousness is supported by genes that are involved in three distinct neurogenetic phases: 1) the emergence of neuron-based consciousness, 2) the continuum of neuronbased consciousness, and 3) the neurodegeneration of human consciousness. The methodology implemented to establish these three neurogenetic phases was a systematic search and evaluation of genes that have been proven to support an active role in one or more of these three phases. This article demonstrates that there is a substructure of gene-based correlates that functions in the three neurogenetic phases. These phases work in tandem with the conscious experience. Consequently, it is established that explanations of human consciousness that rely solely on regions of the brain and neurons are deficient without taking into consideration the neurogenetic element of human consciousness. This presentation of the neurogenetic dimensions of human consciousness is the first of its kind.

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Deletion in Xp22.11: PTCHD1 is a candidate gene for X-linked intellectual disability with or without autism

Cited by 49 publications

References 24 publications

JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling

JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling

Risk factors for autism: translating genomic discoveries into diagnostics

The Neurogenetic Substructures of Human Consciousness

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