Monoamine oxidase deficiency in males with an X chromosome deletion

Molecular Neurogenetics Division, E. K. Shriver Center, Waltham, Massachusetts 02254.
Neuron (Impact Factor: 15.05). 02/1989; 2(1):1069-76. DOI: 10.1016/0896-6273(89)90231-6
Source: PubMed


Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.

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    • "A significant amount of clinical variability exists in ND, outside the ophthalmologic phenotype, with variable phenotypic expression being reported for the hearing loss and cognitive impairments. Specifically, the extra-ocular manifestations of ND include progressive , post-lingual, sensorineural hearing loss (33–100%) [Halpin et al., 2005; Parving and Warburg, 1977], cognitive impairment (50%), behavior disturbance (50%), and seizures [Sims et al., 1989; Lev et al., 2007]. Peripheral vascular disease (PVD) consisting of leg ulcers and varicosities was described in two families [Rehm et al., 1997; Michaelides et al., 2004]. "
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    ABSTRACT: Norrie disease (ND) is an X-linked recessive disorder characterized by congenital blindness, progressive sensorineural hearing loss and cognitive impairment. The ocular phenotype has been well described, while the extraocular manifestations of the disorder are not well understood. We present the data from the Norrie Disease Registry, which consists of 56 patients with detailed clinical histories and genotype data. This study represents the largest, detailed investigation into the phenotypic spectrum of ND to date and more importantly expands knowledge of the extraocular clinical manifestations. We identify several novel aspects of the syndrome that will improve the management of these patients. In particular, we expand our understanding of the neurologic manifestations in ND and identify a chronic seizure disorder in approximately 10% of all patients. In addition, details of the hearing phenotype are described including the median age of onset (12 years of age) and how genotype affects onset. Moreover, we find vascular disease to be a significant component of ND; and vascular health should be, in the future, a component of patient clinical care. In summary, the results expand our understanding of the phenotypic variability and genotypic heterogeneity in ND patients.
    American Journal of Medical Genetics Part A 08/2012; 158A(8):1909-17. DOI:10.1002/ajmg.a.35469 · 2.16 Impact Factor
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    • "As early as the 1960s, a link was made between decreased MAO activity and aggressive behavior in rodents administered MAOA inhibitors [5]. Pintar et al [6] assigned the MAOA gene to the human X chromosome, and some years later, deficient MAOA activity was linked to antisocial behavior in males with an X chromosome deletion [7] and a point Available online at "
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    ABSTRACT: Preclinical and human family studies clearly link monoamine oxidase A (MAOA) to aggression and antisocial personality (ASP). The 30-base pair variable number tandem repeat in the MAOA promoter regulates MAOA levels, but its effects on ASP in humans are unclear. We evaluated the association of the variable number tandem repeat of the MAOA promoter with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, ASP disorder (ASPD) traits in a community sample of 435 participants from the Hopkins Epidemiology of Personality Disorders Study. We did not find an association between the activity of the MAOA allele and ASPD traits; however, among whites, when subjects with a history of childhood physical abuse were excluded, the remaining subjects with low-activity alleles had ASPD trait counts that were 41% greater than those with high-activity alleles (P < .05). The high-activity MAOA allele is protective against ASP among whites with no history of physical abuse, lending support to a link between MAOA expression and antisocial behavior.
    Comprehensive psychiatry 03/2011; 52(2):188-94. DOI:10.1016/j.comppsych.2010.05.005 · 2.25 Impact Factor
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    • "Wuerzburg, Germany, Tel: þ 49 931 201 77810, Fax: þ 49 931 201 77840, E-mail: Neuropsychopharmacology (2005) 30, 1711–1718 & 2005 Nature Publishing Group All rights reserved 0893-133X/05 $30.00 including the MAOA gene, is associated with mental retardation, autistic behavior, motor hyperactivity, and sleep disturbances, which may, at least in part, be attributed to deficient MAO activity (Sims et al, 1989; Murphy et al, 1990). A hemizygous chain termination mutation in exon 8 of MAOA, resulting in an absence of MAOA enzymatic activity in cultured fibroblasts, causes mild mental retardation and episodes of impulsive aggression, arson, and hypersexual behavior, such as attempted rape and exhibitionism, in affected males from a single extended pedigree (Brunner et al, 1993). "
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    ABSTRACT: Genetic variants of the monoamine oxidase A (MAOA) have been associated with aggression-, anxiety-, and addiction-related behavior in several nonclinical and clinical populations. Here, we investigated the influence of allelic variation of MAOA activity on aggression-related personality traits and disease risk in patients with personality disorders. Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to cluster A, B, and C. Personality features were assessed by the revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. The genotype of the MAOA gene-linked polymorphic region (MAOA-LPR) was determined in 566 patients with personality disorders and in 281 healthy controls. MAOA genotype was significantly associated with cluster B personality disorders (chi2=7.77, p=0.005, df=1) but not with cluster C personality disorders. In total, 26.0% of cluster B patients were hemi- or homozygous for the low-activity variant of the MAOA genotype, compared to 16.4% in the control group. Associations between MAOA variants and personality domains related to impulsivity and aggressiveness were inconsistent. Our findings further support the notion that allelic variation of MAOA activity contributes modestly to the balance of hyper- (impulsive-aggressive) and hyporeactive (anxious-depressive) traits.
    Neuropsychopharmacology 10/2005; 30(9):1711-8. DOI:10.1038/sj.npp.1300737 · 7.05 Impact Factor
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