PMID- 30848064
OWN - NLM
STAT- MEDLINE
DCOM- 20200421
LR  - 20200930
IS  - 1552-4833 (Electronic)
IS  - 1552-4825 (Linking)
VI  - 179
IP  - 5
DP  - 2019 May
TI  - Genotype and phenotype correlation in 103 individuals with 2q37 deletion syndrome 
      reveals incomplete penetrance and supports HDAC4 as the primary genetic 
      contributor.
PG  - 782-791
LID - 10.1002/ajmg.a.61089 [doi]
AB  - The 2q37 deletion syndrome, also described in the literature as 
      brachydactyly-mental retardation syndrome (MIM 600430), is caused by deletion or 
      haploinsufficiency of the HDAC4 gene, which encodes the histone deacetylase 4 
      protein. Although the most commonly described hallmark features of the 2q37 
      deletion syndrome include brachydactyly type E, developmental delay, obesity, 
      autistic features, and craniofacial or skeletal dysmorphism, a literature review 
      of 101 published cases plus two newly reported individuals indicates that there 
      is a high degree of variability in the presence of some of the features that are 
      considered the most characteristic of the syndrome: overweight and obesity (34%), 
      cognitive-behavioral issues (79%), dysmorphic craniofacial features (86%), and 
      type E brachydactyly (48%). These features overlap with other neurodevelopmental 
      conditions, including Smith-Magenis syndrome (SMS), and may be incompletely 
      penetrant or demonstrate variable expressivity, depending on the specific 
      chromosomal anomaly. With the advent of fluorescence in situ hybridization 
      (FISH), array-based comparative genomic hybridization, and next-generation DNA 
      sequencing, more detailed molecular diagnoses are possible than in years past, 
      enabling refined characterization of the genotype-phenotype correlation for 
      subjects with 2q37 deletions. In addition, investigations into molecular and gene 
      expression networks are expanding in neurodevelopmental conditions, and we 
      surveyed HDAC4 downstream gene expression by quantitative real-time polymerase 
      chain reaction, further implicating HDAC4 in its role in the regulation of RAI1. 
      Correlation of clinical data defining the impact on downstream gene expression 
      and the potential clinical associations across neurodevelopment will improve our 
      understanding of these complex conditions and potentially lead to common 
      therapeutic approaches.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Le, Trang N
AU  - Le TN
AD  - Department of Pediatrics, Virginia Commonwealth University School of Medicine, 
      Richmond, Virginia.
AD  - Department of Internal Medicine, Division of Endocrinology, Virginia Commonwealth 
      University School of Medicine, Richmond, Virginia.
FAU - Williams, Stephen R
AU  - Williams SR
AD  - Department of Neurology, University of Virginia, Charlottesville, Virginia.
FAU - Alaimo, Joseph T
AU  - Alaimo JT
AD  - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 
      Texas.
FAU - Elsea, Sarah H
AU  - Elsea SH
AUID- ORCID: 0000-0002-1400-8519
AD  - Department of Pediatrics, Virginia Commonwealth University School of Medicine, 
      Richmond, Virginia.
AD  - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 
      Texas.
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University 
      School of Medicine, Richmond, Virginia.
LA  - eng
GR  - Fondation Jerome Lejeune/International
GR  - Virginia Commonwealth University/International
GR  - Baylor College of Medicine/International
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190307
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
RN  - 0 (Repressor Proteins)
RN  - EC 3.5.1.98 (HDAC4 protein, human)
RN  - EC 3.5.1.98 (Histone Deacetylases)
RN  - Chromosome 2q37 deletion syndrome
SB  - IM
CIN - Am J Med Genet A. 2020 Aug;182(8):1861-1864. PMID: 32432407
MH  - Chromosome Deletion
MH  - Chromosomes, Human, Pair 2/genetics
MH  - Developmental Disabilities/genetics
MH  - Female
MH  - Gene Expression
MH  - *Genetic Association Studies
MH  - *Genetic Predisposition to Disease
MH  - *Genotype
MH  - Histone Deacetylases/*genetics
MH  - Humans
MH  - Infant
MH  - Intellectual Disability/genetics
MH  - Male
MH  - Mutation
MH  - *Penetrance
MH  - *Phenotype
MH  - Repressor Proteins/*genetics
OTO - NOTNLM
OT  - HDAC4
OT  - autism spectrum disorder
OT  - behavioral disturbances
OT  - brachydactyly type E
OT  - developmental delay
OT  - obesity
EDAT- 2019/03/09 06:00
MHDA- 2020/04/22 06:00
CRDT- 2019/03/09 06:00
PHST- 2018/04/20 00:00 [received]
PHST- 2019/01/02 00:00 [revised]
PHST- 2019/02/05 00:00 [accepted]
PHST- 2019/03/09 06:00 [pubmed]
PHST- 2020/04/22 06:00 [medline]
PHST- 2019/03/09 06:00 [entrez]
AID - 10.1002/ajmg.a.61089 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2019 May;179(5):782-791. doi: 10.1002/ajmg.a.61089. Epub 2019 
      Mar 7.