PMID- 28504353
OWN - NLM
STAT- MEDLINE
DCOM- 20171201
LR  - 20200930
IS  - 1552-4833 (Electronic)
IS  - 1552-4825 (Linking)
VI  - 173
IP  - 8
DP  - 2017 Aug
TI  - CMIP haploinsufficiency in two patients with autism spectrum disorder and 
      co-occurring gastrointestinal issues.
PG  - 2101-2107
LID - 10.1002/ajmg.a.38277 [doi]
AB  - 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.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Luo, Minjie
AU  - Luo M
AUID- ORCID: 0000-0002-5788-3962
AD  - Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, 
      The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
AD  - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at 
      the University of Pennsylvania, Philadelphia, Pennsylvania.
FAU - Fan, Jinbo
AU  - Fan J
AD  - Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, 
      The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
FAU - Wenger, Tara L
AU  - Wenger TL
AD  - Department of Pediatrics, Seattle Children's Hospital, Seattle, Washington.
FAU - Harr, Margaret H
AU  - Harr MH
AD  - Division of Craniofacial Medicine, Division of Human Genetics, Department of 
      Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
FAU - Racobaldo, Melissa
AU  - Racobaldo M
AD  - Department of Pediatrics, Division of Genetics and Metabolism, University of 
      South Florida College of Medicine, Tampa, Florida.
FAU - Mulchandani, Surabhi
AU  - Mulchandani S
AD  - Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, 
      The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
FAU - Dubbs, Holly
AU  - Dubbs H
AD  - Division of Neurology, Department of Pediatrics, The Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania.
FAU - Zackai, Elaine H
AU  - Zackai EH
AD  - Division of Craniofacial Medicine, Division of Human Genetics, Department of 
      Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
AD  - Department of Genetics, Perelman School of Medicine at the University of 
      Pennsylvania, Philadelphia, Pennsylvania.
FAU - Spinner, Nancy B
AU  - Spinner NB
AD  - Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, 
      The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
AD  - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at 
      the University of Pennsylvania, Philadelphia, Pennsylvania.
FAU - Conlin, Laura K
AU  - Conlin LK
AD  - Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, 
      The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
AD  - Department of Pathology and Laboratory Medicine, Perelman School of Medicine at 
      the University of Pennsylvania, Philadelphia, Pennsylvania.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20170515
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CMIP protein, human)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*genetics
MH  - Adolescent
MH  - Autism Spectrum Disorder/complications/*genetics/physiopathology
MH  - Developmental Disabilities/genetics/physiopathology
MH  - Exons
MH  - Gastrointestinal Diseases/complications/*genetics/physiopathology
MH  - Haploinsufficiency/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Phenotype
MH  - Sequence Deletion/genetics
OTO - NOTNLM
OT  - CMIP
OT  - SNP array
OT  - autism
EDAT- 2017/05/16 06:00
MHDA- 2017/12/02 06:00
CRDT- 2017/05/16 06:00
PHST- 2016/10/10 00:00 [received]
PHST- 2017/04/10 00:00 [accepted]
PHST- 2017/05/16 06:00 [pubmed]
PHST- 2017/12/02 06:00 [medline]
PHST- 2017/05/16 06:00 [entrez]
AID - 10.1002/ajmg.a.38277 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2017 Aug;173(8):2101-2107. doi: 10.1002/ajmg.a.38277. Epub 2017 
      May 15.