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Am J Med Genet A. 2017 Aug;173(8):2101-2107. doi: 10.1002/ajmg.a.38277. Epub 2017 May 15.

CMIP haploinsufficiency in two patients with autism spectrum disorder and co-occurring gastrointestinal issues.

Author information

1
Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
2
Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
3
Department of Pediatrics, Seattle Children's Hospital, Seattle, Washington.
4
Division of Craniofacial Medicine, Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
5
Department of Pediatrics, Division of Genetics and Metabolism, University of South Florida College of Medicine, Tampa, Florida.
6
Division of Neurology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
7
Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Abstract

Autism spectrum disorder (ASD) is a genetically heterogeneous group of disorders characterized by impairments in social communication and restricted interests. Though some patients with ASD have an identifiable genetic cause, the cause of most ASD remains elusive. Many ASD susceptibility loci have been identified through clinical studies. We report two patients with syndromic ASD and persistent gastrointestinal issues who carry de novo deletions involving the CMIP gene detected by genome-wide SNP microarray and fluorescence in situ hybridization (FISH) analysis. Patient 1 has a 517 kb deletion within 16q23.2q23.3 including the entire CMIP gene. Patient 2 has a 1.59 Mb deletion within 16q23.2q23.3 that includes partial deletion of CMIP in addition to 12 other genes, none of which have a known connection to ASD or other clinical phenotypes. The deletion of CMIP is rare in general population and was not found among a reference cohort of approximately 12,000 patients studied in our laboratory who underwent SNP array analysis for various indications. A 280 kb de novo deletion containing the first 3 exons of CMIP was reported in one patient who also demonstrated ASD and developmental delay. CMIP has previously been identified as a susceptibility locus for specific language impairment (SLI). It is notable that both patients in this study had significant gastrointestinal issues requiring enteral feedings, which is unusual for patients with ASD, in addition to unusually elevated birth length, further supporting a shared causative gene. These findings suggest that CMIP haploinsufficiency is the likely cause of syndromic ASD in our patients.

KEYWORDS:

CMIP; SNP array; autism

PMID:
28504353
DOI:
10.1002/ajmg.a.38277
[Indexed for MEDLINE]

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