Clin Genet 2011: 79: 79 – 85 Printed in Singapore. All rights reserved  2010 John Wiley & Sons A/S CLINICAL GENETICS doi: 10.1111/j.1399-0004.2010.01590.x Short Report Deletion in Xp22.11: PTCHD1 is a candidate gene for X-linked intellectual disability with or without autism Filges I, R¨ othlisberger 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. Clin Genet 2011: 79: 79–85.  John Wiley & Sons A/S, 2010 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. Conflict of interest The authors declare no conflict of interest. I Filges a ,BR¨ othlisberger b , A Blattner b , N Boesch a , P Demougin c , F Wenzel a , AR Huber b , K Heinimann a , P Weber d and P Miny a a Division of Medical Genetics, University Children’s Hospital and Department of Biomedicine, Basel, Switzerland, b Center of Laboratory Medicine, Cantonal Hospital, Aarau, Switzerland, c Life Sciences Training Facility, University of Basel, Basel, Switzerland, and d Division of Neuropediatrics and Developmental Medicine, University Children’s Hospital, Basel, Switzerland Key words: aCGH – autism – candidate gene – deletion in Xp22.11 – intellectual disability – PTCHD1 – X-linked inheritance Corresponding author: Dr Isabel Filges, Division of Medical Genetics, University Children’s Hospital and Department of Biomedicine, R ¨ omergasse 8, CH-4005 Basel, Switzerland. Tel.: +41 61 685 6794; fax: +41 61 685 6011; e-mail: Isabel.Filges@unibas.ch Received 27 June 2010, received and accepted for publication 28 October 2010 Numerous single genes have been shown to be implicated in the origin of intellectual disability (ID) inherited in an autosomal dominant, autoso- mal recessive or X-linked recessive manner. The most common known cause of X-linked intellec- tual disability (XLID) is the fragile X-syndrome because of an expansion of the trinucleotide repeat CGG in the FMR1 gene. In total, more than 90 additional genes involved in syndromic or non-syndromic forms of XLID have been iden- tified through genetic linkage analysis, positional cloning, candidate gene analysis or cytogenetic studies (1–4). However, these mutations each present only in a small fraction of affected families (3). Additionally, copy number (CN) variation has been shown to play a significant role in the aeti- ology of developmental disabilities including non- syndromic intellectual impairment and/or autism disorders (5–7). A major proportion of these are larger deletions, duplications or segmental aneu- ploidies that affect multiple genes, and a number of studies indicate that they account for up to 10% of non-syndromic ID (8, 9) and for up to 5–10% 79