ClinGen Dosage Sensitivity Curation Page

Xp11.23 region (includes MAOA and MAOB)

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
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.
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.
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.

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.

Evidence for Triplosenstive Phenotype

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.

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.