1q21.1 recurrent (TAR syndrome) region (proximal, BP2-BP3) (includes RBM8A)
  • 1
    Haplo
    Score
  • 1
    Triplo
    Score

Region Facts

Region Name
1q21.1 recurrent (TAR syndrome) region (proximal, BP2-BP3) (includes RBM8A)
Cytoband
1q21.1
Genomic Coordinates
GRCh37/hg19 chr1:145386507-145748064 NCBI Ensembl UCSC
GRCh38/hg38 chr1:145686999-146048495 NCBI Ensembl UCSC

Dosage Sensitivity Summary (Region)

Dosage ID:
ISCA-37428
Curation Status:
Complete
Issue Type:
Dosage Curation - Region
Description:
The 1q proximal region contains a cluster of low copy repeats that mediate recurrent copy number changes through non-allelic homologous recombination. This review refers to CNVs involving recurrent breakpoint (BP) regions BP2 and BP3. Note that genes used as landmarks are not necessarily causative of the complete phenotype(s) associated with the region.
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
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Triplosensitivity:
Little Evidence for Triplosensitivity (1)
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Related Links:
Last Evaluated:
05/18/2017

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • thrombocytopenia-absent radius syndrome Monarch
HI Evidence:
  • PUBMED: 22317977
    Rosenfeld et al (2012) provided a clinical characterization of 22 individuals carrying deletions for this region who do not meet clinical criteria for TAR syndrome, an autosomal recessive disease caused by compound heterozygosity with mutation in the gene RBM8A. Features present in any one individual were variable, and features present in 50% or more of individuals included: failure to thrive/feeding problems and developmental delay/intellectual disabilities.
  • PUBMED: 25217958
    Coe et al. (2014) performed a large-scale case-control comparison study of the relative prevalence of copy number variants in children with ID/DD, MCA, and other developmental phenotypes compared to controls. 1q21 (BP2-BP3, RBM8A) proximal region deletions were observed in 25/29,085 cases versus 2/19,584 controls (p=1.63E-04), demonstrating enrichment of this deletion in the clinical population. See also Cooper et al. (2011) PMID 21841781 and Rosenfeld et al. (2013) PMID 23258348. NOTE: these comparisons are complicated by the apparent inclusion of patients with TAR syndrome in the clinical population used in these studies.
HI Evidence Comments:
Evidence in support of a pathogenic role for deletion of this region is limited at this time. Although deletions of this region have been shown to be significantly enriched in the clinical population, prevalence estimates are complicated by apparent inclusion of TAR syndrome (compound heterozygosity for RBM8A gene mutation) patients in these estimates, and thus far there is only a single publication with phenotypic descriptions of proximal 1q21.1 deletion carriers, in whom the phenotype appears to be both variably expressive and incompletely penetrant. Therefore the current haploinsufficiency score is 1. Deletion of this region is a susceptibility factor for thrombocytopenia-absent radius (TAR) syndrome (OMIM 274000), an autosomal recessive disorder characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia in the presence of both thumbs. Most patients with TAR syndrome have a deletion of the proximal 1q21.1 region on one chromosome 1 homolog and a point mutation in the regulatory region for the gene RBM8A on the other chromosome 1 homolog (see Gene Reviews http://www.ncbi.nlm.nih.gov/books/NBK23758/ and Albers et al 2012; PMID: 22366785). Note also that cognitive development is usually normal in patients with TAR syndrome.

Triplosensitivity (TS) Score Details

TS Score:
1
TS Evidence Strength:
Little Evidence for Triplosensitivity (Disclaimer)
TS Published Evidence:
  • PUBMED: 22317977
    Rosenfeld et al (2012) provided a clinical characterization of 20 individuals carrying duplications for this region. Features present in any one individual were variable, and features present in 50% or more of individuals included: developmental delay, intellectual disability, dysmorphic features, brain anomalies, failure to thrive/feeding problems, and behavioral problems.
  • PUBMED: 25217958
    Coe et al. (2014) performed a large-scale case-control comparison study of the relative prevalence of copy number variants in children with ID/DD, MCA, and other developmental phenotypes compared to controls, 1q21 (BP2-BP3, RBM8A) proximal region duplications were observed in 56/29,085 cases versus 11/19,584 controls (p=2.37E-05), demonstrating enrichment of this duplication in the clinical population. See also Cooper et al. (2011) PMID 21841781 and Rosenfeld et al. (2013) PMID 23258348.
TS Evidence Comments:
Evidence in support of the pathogenicity of duplication of this region is limited at this time. Although duplications of this region have been shown to be significantly enriched in the clinical population, thus far there is only a single publication with phenotypic descriptions of proximal 1q21.1 duplication carriers, in whom the phenotype appears to be both variably expressive and incompletely penetrant. Therefore the current triplosensitivity score is 1.

Genomic View

Select assembly: (NC_000001.10) ()