Xq28 recurrent region (includes GDI1)

  • 0
    Haplo
    Score
  • 3
    Triplo
    Score

Region Facts

Region Name
Xq28 recurrent region (includes GDI1)
Cytoband
Xq28
Genomic Coordinates
GRCh37/hg19 chrX:153624564-153783898 NCBI Ensembl UCSC
GRCh38/hg38 chrX:154396223-154555683 NCBI Ensembl UCSC

Dosage Sensitivity Summary (Region)

Dosage ID:
ISCA-37439
Curation Status:
Complete
Issue Type:
Dosage Curation - Region
Description:
The distal Xq28 region contains a cluster of low copy repeats that mediate copy number changes through non-allelic homologous recombination. This review refers to CNVs involving recurrent breakpoints regions K1/K2 and L1/L2. Note that genes used as landmarks are not necessarily causative of the complete phenotype(s) associated with the region.
Haploinsufficiency:
No Evidence for Haploinsufficiency (0)
Triplosensitivity:
Sufficient Evidence for Triplosensitivity (3)
Related Links:
Last Evaluated:
05/26/2016

Haploinsufficiency (HI) Score Details

HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency (Disclaimer)
HI Evidence Comments:
No published descriptions of reciprocal deletions of this full region yet, although deletions involving FLNA, TAZ and other genes individually are known.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
3
TS Evidence Strength:
Sufficient Evidence for Triplosensitivity (Disclaimer)
TS Disease:
  • chromosome Xq28 duplication syndrome Monarch
TS Published Evidence:
  • PUBMED: PMID:20004760
    Vandelwalle et al. report an approximate 0.3Mb recurrent, variable copy-number gain region within Xq28 segregating with disease amongst 4 unrelated X-linked intellectual disability families. Though there are 18 annotated genes in the region, GDI1 is proposed by these authors to be the most likely candidate gene, as the copy number of GDI1 appears to correlate with severity. Moreover, expression analysis revealed copy-number-dependent increased mRNA levels in affected patients compared to control individuals. The copy number gain was not found in 138 X chromosomes from controls.
  • PUBMED: PMID:17546640
    Froyen et al, 2008: A 0.3 Mb duplication of Xq28 including GDI1 was found to segregate with disease (intellectual disability and mild ataxia) within a family of three affected individuals.
  • PUBMED: 18047645
    Madrigal et al, 2007: A 250-kb duplication including GDI1, FLNA and EMD genes (but not MECP2) was identified in a male proband, two affected male relatives and two carrier females. The proband exhibited mild intellectual disability, neonatal seizures, motor delay, microcephaly, hyperkinesias and mild dysmorphic features. RT-PCR studies revealed a significantly higher GDI1 expression in the proband and his affected uncle compared to four male controls. The carrier mother showed preferential and complete inactivation of the X-chromosome inherited by the proband (i.e., carrying the 250-kb duplication).
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

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