Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder. (14th October 2014)

• Record Type: Journal Article
• Authors: Chaudhry, A.; Noor, A.; Degagne, B.; Baker, K.; Bok, L. A.; Brady, A. F.; Chitayat, D.; Chung, B. H.; Cytrynbaum, C.; Dyment, D.; Filges, I.; Helm, B.; Hutchison, H. T.; Jeng, L. J. B.; Laumonnier, F.; Marshall, C. R.; Menzel, M.; Parkash, S.; Parker, M. J.; The DDD Study; Raymond, L. F.; Rideout, A. L.; Roberts, W.; Rupps, R.; Schanze, I.; Schrander‐Stumpel, C. T. R. M.; Speevak, M. D.; Stavropoulos, D. J.; Stevens, S. J. C.; Thomas, E. R. A.; Toutain, A.; Vergano, S.; Weksberg, R.; Scherer, S. W.; Vincent, J. B.; Carter, M. T.;
• Is Part Of: Clinical genetics. Volume 88:Number 3(2015:Sep.)
• Page Start: 224
• Page End: 233
• Publication Date: 2014-10-14
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12482
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12482-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12482-para-0001">Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as <italic>NRXN1</italic>, <italic>SHANK2</italic>, <italic>SHANK3</italic> and <italic>PTCHD1</italic>. Deletions have been reported in <italic>PTCHD1</italic> however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with <italic>PTCHD1</italic> deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the <italic>PTCHD1</italic> coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD‐like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous <italic>PTCHD1</italic> loss of function causes an X‐linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype.</p> </abstract>