Xp11.23 region (includes MAOA and MAOB)
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Region Facts

Region Name
Xp11.23 region (includes MAOA and MAOB)
Cytoband
Xp11.23
Genomic Coordinates
GRCh37/hg19 chrX:43514154-43741720 NCBI Ensembl UCSC
GRCh38/hg38 chrX:43654906-43882474 NCBI Ensembl UCSC

Dosage Sensitivity Summary (Region)

Dosage ID:
ISCA-37468
Curation Status:
Complete
Issue Type:
Dosage Curation - Region
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
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Triplosensitivity:
No Evidence for Triplosensitivity (0)
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Related Links:
Last Evaluated:
10/11/2017

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Evidence:
  • PUBMED: 22365943
    O'Leary et al. (2012) report a de novo deletion involving only the MAOA and MAOB genes in a male infant with developmental delay, episodic hypotonia, dysmorphic features, and stereotypical hand movements.
  • PUBMED: 20485326
    Whibley et al. (2010) report a maternally inherited 240 kb deletion encompassing exons 2-15 of MAOA and all of MAOB in two brothers with intellectual disability, episodic hypotonia, and stereotypical hand movements.
  • PUBMED: 23414621
    Saito et al 2014 report two male siblings with a de novo 800 kb deletion involving only the MAOA and MAOB genes. The siblings had severe developmental delays, dysmorphic features, stereotypical hand movements, and episodes of “sudden muscle tone loss” (episodic hypotonia, as described in Whibley et al 2010) with normal EEG findings.
HI Evidence Comments:
Deletions of MAOA and MAOB appear to be correlated with a phenotype involving intellectual disability, episodic hypotonia (resembling seizures but without EEG correlate), and anomalies in levels of catecholamines and their metabolites. Affected individuals have also been reported with varying degrees of dysmorphic features and behavioral issues. Deletions of MAOA and MAOB have frequently been seen as part of larger, contiguous gene deletions, and often include the nearby NDP gene associated with Norrie disease. In addition to the characteristic features of Norrie disease, individuals with deletions also encompassing MAOA and MAOB are said to have more severe neuropsychological impairment. Individuals with deletions involving only NDP and MAOB have been reported, and their features are said to be consistent with Norrie disease, but without the intellectual or behavioral issues seen in individuals with larger deletions including MAOA (PMID: 8613523). Therefore, though this suggests that the loss of MAOA may be responsible for the neuropsychiatric phenotype, there is not enough evidence to definitively support this at this time; no deletions involving MAOA alone have been reported to date, and only two families with predicted loss of function mutations (a nonsense mutation in exon 8 and a frameshift mutation in exon 5 of MAOA) have been reported (PMID:8503438 and 25807999, respectively). Additionally, both MAOA and MAOB appear to be intolerant to loss of function mutations based on ExAC data.
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:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
A 500 kb duplication involving MAOA, MAOB, and NDP has been reported in a male with intellectual disability and epilepsy (PMID:20808325). As this duplication has been shown to include NDP, it is not considered as evidence toward the triplosensitivity of the MAOA/MAOB region discussed here.
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

Select assembly: (NC_000023.10) ()