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

• Published in: Clinical genetics Vol. 79; no. 1; pp. 79 - 85
• Main Authors: Filges, I, Röthlisberger, B, Blattner, A, Boesch, N, Demougin, P, Wenzel, F, Huber, AR, Heinimann, K, Weber, P, Miny, P
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-2011; Wiley-Blackwell
• Subjects: aCGH; Adult and adolescent clinical studies; Autism; Autistic Disorder - genetics; Autistic Disorder - physiopathology; Biological and medical sciences; candidate gene; Child; Chromosomes; Chromosomes, Human, X; deletion in Xp22.11; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genes; Genes, X-Linked; Genetics of eukaryotes. Biological and molecular evolution; Humans; Indexing in process; Intellectual deficiency; intellectual disability; Intellectual Disability - genetics; Intellectual Disability - physiopathology; Male; Medical genetics; Medical sciences; Mental disorders; Molecular and cellular biology; Patched Receptors; Pedigree; Phenotype; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; PTCHD1; Receptors, Cell Surface - genetics; Sequence Deletion; X-linked inheritance; Young Adult; Chromosomal aberration; Sex linked character; Pathogenesis; Inheritance; Developmental disorder; Mental retardation; Genetic determinism; X-linked inheritance; aCGH; PTCHD1; Deletion; Genetics; X-Chromosome; Neurological disorder; Handicap; Human; Nervous system diseases; Abnormal X chromosome; Genetic disease; Autism; candidate gene; deletion in Xp22.11; Intellectual deficiency; Abnormal chromosome; intellectual disability
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2010.01590.x

Filges I, Röthlisberger B, Blattner A, Boesch N, Demougin P, Wenzel F, Huber AR, Heinimann K, Weber P, Miny P. Deletion in Xp22.11: PTCHD1 is a candidate gene for X‐linked intellectual disability with or without autism.
Submicroscopic chromosomal anomalies play an important role in the aetiology of intellectual disability (ID) and have been shown to account for up to 10% of non‐syndromic forms. We present a family with two affected boys compatible with X‐linked inheritance of a phenotype of severe neurodevelopmental disorder cosegregating with a deletion in Xp22.11 exclusively containing the PTCHD1 gene. Although the exact function of this gene is unknown to date, the structural overlap of its encoded patched domain‐containing protein 1, the transmembrane protein involved in the sonic hedgehog pathway, and its expression in human cortex and cerebellum as well as in mice and drosophila brain suggests a causative role of its nullisomy in the developmental phenotype of our family. Our findings support the recent notions that PTCHD1 may play a role in X‐linked intellectual disability (XLID) and autism disorders.