ClinGen Dosage Sensitivity Curation Page

MAOA

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
8211186 Selective MAO-A deficiency has been described in a large Dutch kindred with borderline mental retardation and abnormal behavior. Affected individuals in this pedigree had a point mutation that prematurely truncated the MAO-A protein.

Haploinsufficiency phenotype comments:

Notably, focal deletions involving only MAOA have not been reported in the literature. The MAOA and MAOB genes are located next to each other in Xp11.3-11.4. Deletions encompassing both MAOA and MAOB genes have been reported and lead to intellectual disability and behavioral problems in males (see PMIDs 20485326 and 22365943 for examples). Larger deletions extending to the adjacent NDP gene have also been reported and are associated with an atypical presentation of Norrie disease (MIM:310600) Several studies have shown an association of SNPs in MAOA with various pathological behavioral traits (PMIDs 16896926, 22297589, 22832821, 21628708). However, the associated behavioral phenotypes are non-specific and the evidence base weak.

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 score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

Notably, focal duplications involving only MAOA have not been reported in the literature. Klitten et al reported a male patient with mental retardation and intractable epilepsy carrying a duplication of Xp11.3 that involved the MAOA, MAOB, and NDP genes (PMID: 20808325)

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.