Collins F A, Murphy D L, Reiss A L, Sims K B, Lewis J G, Freund L, Karoum F, Zhu D, Maumenee I H, Antonarakis S E
Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Am J Med Genet. 1992 Jan 1;42(1):127-34. doi: 10.1002/ajmg.1320420126.
Norrie disease is a rare X-linked recessive disorder characterized by blindness from infancy. The gene for Norrie disease has been localized to Xp11.3. More recently, the genes for monoamine oxidase (MAOA, MAOB) have been mapped to the same region. This study evaluates the clinical, biochemical, and neuropsychiatric data in an affected male and 2 obligate heterozygote females from a single family with a submicroscopic deletion involving Norrie disease and MAO genes. The propositus was a profoundly retarded, blind male; he also had neurologic abnormalities including myoclonus and stereotopy-habit disorder. Both obligate carrier females had a normal IQ. The propositus' mother met diagnostic criteria for "chronic hypomania and schizotypal features." The propositus' MAO activity was undetectable and the female heterozygotes had reduced levels comparable to patients receiving MAO inhibiting antidepressants. MAO substrate and metabolite abnormalities were found in the propositus' plasma and CSF. This study indicates that subtle biochemical and possibly neuropsychiatric abnormalities may be detected in some heterozygotes with the microdeletion in Xp11.3 due to loss of the gene product for the MAO genes; this deletion can also explain some of the complex phenotype of this contiguous gene syndrome in the propositus.
诺里病是一种罕见的X连锁隐性疾病，其特征为婴儿期失明。诺里病基因已定位到Xp11.3。最近，单胺氧化酶（MAOA、MAOB）基因也被定位到同一区域。本研究评估了来自一个单一家族的一名患病男性和两名必然杂合子女性的临床、生化及神经精神学数据，该家族存在涉及诺里病和MAO基因的亚显微缺失。先证者是一名严重智力发育迟缓的失明男性；他还存在包括肌阵挛和刻板行为障碍在内的神经学异常。两名必然携带者女性的智商均正常。先证者的母亲符合“慢性轻躁狂和分裂样特征”的诊断标准。先证者的MAO活性检测不到，女性杂合子的MAO水平降低，与接受MAO抑制性抗抑郁药治疗的患者相当。在先证者的血浆和脑脊液中发现了MAO底物和代谢产物异常。本研究表明，由于MAO基因产物缺失，在一些Xp11.3存在微缺失的杂合子中可能检测到细微的生化异常以及可能的神经精神学异常；这种缺失也可以解释先证者这种相邻基因综合征的一些复杂表型。
