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Monoamine oxidases (MAO-A and MAO-B) have a key role in the degradation of amine neurotransmitters, such as dopamine, norepinephrine and serotonin. We identified an inherited 240 kb deletion on Xp11.3-p11.4, which encompasses both monoamine oxidase genes but, unlike other published reports, does not affect the adjacent Norrie disease gene (NDP). The brothers who inherited the deletion, and thus have no monoamine oxidase function, presented with severe developmental delay, intermittent hypotonia and stereotypical hand movements . The rapid degradation of bioactive monoamines by MAO isoenzymes is essential for appropriate synaptic neurotransmission, and monoaminergic signalling affects motor, perceptual, cognitive and emotional brain functions. 2 The MAOA and MAOB genes occur in tandem, suggesting an ancestral duplication event, but lie in opposite orientations on Xp11.23, where they share 70% identity at the amino-acid level and exhibit an identical organization of their 15 exons. 3,4 Despite this sequence similarity, MAO-A and MAO-B have distinct but overlapping substrate specificities and spatial and temporal expression patterns in the brain and peripheral tissues, although most tissues express both isoenzymes. [5][6][7] Previous reports of MAO gene deletions have always encompassed the adjacent NDP gene and are associated with an atypical presentation of Norrie disease (ND, OMIM no. 310600). ND is a neurodevelopmental disorder characterized by congenital blindness because of bilateral retinal malformation and lens opacity. To date, over 70 pathogenic NDP mutations have been identified. 8-10 Accessory phenotypes in 'classical' ND include progressive sensorineural deafness in approximately one-third of cases and some degree of intellectual disability, autism or psychosis in over 50% of cases. 11 Atypical ND patients with a contiguous deletion of NDP and both MAO genes

Introduction: Monosomy 1p36 is one of the most common terminal deletion syndromes, with an approximate incidence of 1 in every 5000 live births. This syndrome is associated with several pronounced clinical features including characteristic facial features, cardiac abnormalities, seizures and mental retardation, all of which are believed to be due to haploinsufficiency of genes within the 1p36 region. The deletion size varies from approximately 1.5 Mb to 10 Mb with the most common breakpoints located at 1p36.13 to 1p36.33. Over 70% of 1p36 deletion patients have a true terminal deletion. A further 7% have interstitial deletions and a proportion have a derivative chromosome 1 where the 1p telomere is replaced by material from another chromosome, either as a result of a de-novo rearrangement or as a consequence of malsegregation of a balanced parental translocation at meiosis.