2q37.3 terminal region (includes HDAC4)

  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Region Facts

Region Name
2q37.3 terminal region (includes HDAC4)
Cytoband
2q37.3
Genomic Coordinates
GRCh37/hg19 chr2:239954693-242930600 NCBI Ensembl UCSC
GRCh38/hg38 chr2:239032997-241988449 NCBI Ensembl UCSC

Dosage Sensitivity Summary (Region)

Dosage ID:
ISCA-37394
Curation Status:
Complete
Issue Type:
Dosage Curation - Region
Description:
DELETION INFO: ISCA P Value: ND EICHLER P Value: 0.0001 OMIM: #600430 SEG DUP mediated: No REFS: Reference 1: Casas, et al., Am J Med Genet. 130:331-339, 2004; PMID: 15386475 ; Reference 2: Doherty, et al. GeneReviews. URL: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=del2q37_2
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
06/13/2016

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 19752160
    This paper studied 52 Smith-Magenis syndrome-like patients that were RAI1 negative. Array CGH was used to scan for CNVs. Two patients harbor 2q37.3 deletions of unknown inheritance: one at chr2:240,099,656-241,289,872 and the other at chr2:238,256,217-241,289,874 (hg19). Both patients have midface hypoplasia, brachydactyly type E, and abnormal behavior.
  • PUBMED: 23188045
    The authors studied a 3-generation family with psychomotor and behavioral abnormalities plus dysmorphism (midface hypoplasia, deep-set eyes, thin upper lip), but no brachydactyly. Array CGH analysis on available samples (2/3 affected individuals) revealed an interstitial 2q37.3 deletion including the HDAC4 and TWIST2 genes and a noncoding RNA (hg18:chr2:239,395,957-240,154,599). The authors conclude that the HDAC4 gene represents the BDMR critical region and that their findings are consistent with previously reported incomplete penetrance of the brachydactyly phenotype.
  • PUBMED: 25402011
    This is a report of a family with brachydactyly type E and some mild dysmorphic features, but no intellectual disability. A 2q37.3 microdeletion was detected in all affected family members that were tested via aCGH: arr[hg19] 2q37.3(239,720,311-240,211,233)x1. This interval includes part of HDAC4, TWIST2, and noncoding RNAs.
HI Evidence Comments:
The coordinates of this region represent the minimal deleted region required for the BDMR phenotype. Deletions that extend proximally may carry a risk of congenital heart defects [PMID 15173228]. Note that genes used as landmarks are not necessarily causative of the complete phenotype(s) associated with the region. Additional studies: PMID 15173228: This study used multiplex amplifiable probe hybridization to refine the deleted region in patients with known monosomy 2q37 ("Albright hereditary osteodystrophy (AHO)-like metacarpal/metatarsal shortening brachymetaphalangism aka brachydactyly-mental retardation/BDMR syndrome"). No common breakpoints were found and they concluded that the minimum deleted region in patients with facial dysmorphism and brachymetaphalangism is approximately 3 Mb: from HDAC4 at ~240.0 Mb (hg19) to the telomere. Cases were noted to have developmental delay and facial dysmorphism (round face, flattened nasal bridge, deep-set eyes, up-slanting palpebral fissures, anteverted nares, thin upper lip) and sometimes: brachydactyly (55%), behavioral abnormalities, seizures, eczema, and/or heart defects. Considerable clinical variability was noted. PMID 16762827: This study used FISH to analyze 5 patients with cytogenetically-visisble de novo monosomy 2q37. Four patients had different terminal dels, one interstitial. They concluded that the minimum deleted region in patients with BDMR is approximately from RP11-585E12 to RP11-351E10 (~238.1-242.9 Mb, hg19). PMID 26112830: One case (case #1) of a de novo 2q37.3 deletion in a patient with developmental delay, brachydactyly type E, round face, hypoplastic midface, flat nasal bridge, and small deep-set eyes at hg19 237.7-243.0 Mb (proband tested by aCGH, parents by FISH). PMID 19365831: One case of a de novo 2q37.3 deletion in a patient with autism, mild intellectual disability, and brachymetaphalangy; no facial dysmorphism was observed (proband tested by aCGH, parents by FISH). The deletion observed is a 3.5 Mb terminal deletion with the proximal break point between 239.1-240.0 Mb. PMID 25329715: One patient (# 2) was found by aCGH to have a 2q37.3 deletion from hg19 240.9-243.2, inheritance unknown. This patient has no dysmorphisms and only mild delays, but was noted to have behavior abnormalities. Patient was reported to be negative for BDMR features.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Two duplications of this region are noted in ClinVar: hg19 ~chr2:236.2-243.1 and chr2:236.5-243.0. These duplications were from "An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities" by Kaminsky et al [PMID 21844811]. However, no further evidence exists at this time.

Genomic View

Select assembly: (NC_000002.11) ()