Rare Disease Day, our Roma cousins and the power of one
Rare Disease Day, our Roma cousins and the power of one
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罕见病日，我们的罗姆表亲和一个人的力量
DOI：
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发表时间：
2012
影响因子：
2.9
通讯作者：
D. P. Kasbekar
中科院分区：
文献类型：
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作者：
D. P. Kasbekar
声援患有这些罕见疾病的患者及其家人，强调罕见疾病研究的重要性，并提高公众对这些疾病的认识。这一天在随后的三年中的2月28日被观察到。核糖-5-磷酸异构酶（RPI）缺乏症被认为是最罕见的疾病，只有一个诊断病例（Wamelink等人，2010 J. Mol. Med.88931 -939）。患者患有进行性脑白质疾病和周围神经病变。代谢分析显示他的大脑和体液中D-核糖醇和D-阿糖醇的含量升高。遗传学分析表明，这两个等位基因的RPI基因突变的病人。一个等位基因具有移码突变，其引入提前终止密码子并代表非功能性无效等位基因，另一个具有错义转换突变（c. C182 T），其在密码子61处用丙氨酸取代缬氨酸并产生部分功能性酶。错义等位基因也表现出细胞类型依赖性表达缺陷，例如一些细胞（成淋巴细胞）表现出残留的RPI mRNA表达和酶活性，但在其他细胞（成纤维细胞）中，缺陷是完全的。据推测，由于转换突变位于外显子3的第一个密码子，其邻近剪接受体位点可能会影响特定细胞中RPI mRNA的成熟，或改变其与另一种调节分子的结合。影响RPI活性的三个缺陷的结合-无效等位基因、具有RPI mRNA的细胞类型依赖性减少的等位基因和部分活性RPI酶-比两个无效等位基因的双杂合性的自然和可能致命的发生更罕见，并且将解释患者的独特性。一种疾病可能在世界的某个地方很罕见，但在另一个地方却很常见。原发性先天性青光眼（PCG）是一种常染色体隐性遗传眼病，在罗姆人中发生率异常高（1：1250出生）。罗姆人是大约1000至1500年前从印度西北部作为吉普赛人迁移到欧洲的少数民族的后裔。目前，欧洲约有800万人。他们看起来如此印度，我甚至试图用印地语与我在巴黎歌剧院附近看到的几个乞讨游客交谈。LTBP 2基因的终止突变与一类罗姆人的发育性青光眼有关。Ali等人（2009 Am. J.哈姆。Genet. 84 664-671）发现，这种终止突变，沿着14个侧翼SNP，是共享的。
to express solidarity with patients who have these rare diseases and their families, to highlight the importance of research on rare diseases, and to raise public awareness about them. This day was observed on February 28 in the subsequent three years. Ribose-5-phosphate isomerase (RPI) deficiency is considered the rarest disease, with only one diagnosed case (Wamelink et al. 2010 J. Mol. Med. 88 931–939). The patient suffered from progressive brain white-matter disease and peripheral neuropathy. Metabolic profiling showed elevated levels of D-ribitol and D-arabitol in his brain and body fluids. Genetic analysis revealed that both alleles of the RPI gene were mutant in the patient. One allele had a frameshift mutation that introduced a premature termination codon and represented a non-functional null allele, and the other had a missense transition mutation (c. C182T) that substituted an alanine for valine at codon 61 and generated a partially functional enzyme. The missense allele also showed cell-type-dependent expression deficits, such that some cells (lymphoblasts) showed residual RPI mRNA expression and enzyme activity but in other cells (fibroblasts) the deficit was complete. It was speculated that since the transition mutation was in the first codon of exon 3, its proximity to the splice acceptor site might affect the maturation of RPI mRNA in specific cells, or alter its binding to another regulatory molecule. The conjunction of three defects affecting RPI activity – a null allele, an allele with a cell-type-dependent reduction in RPI mRNA and a partially active RPI enzyme – is rarer than the natural and presumably lethal occurrence of double heterozygosity for two null alleles, and would account for the patient's uniqueness. A disease may be rare in one part of the world yet common in another. Primary congenital glaucoma (PCG), an autosomal recessive eye disease, occurs at an unusually high frequency (1:1250 births) among the Roma. The Roma are descendants of small populations of people who migrated from northwest India to Europe as gypsies about 1000 to 1500 years ago. Their number in Europe now is about 8 million. They look so Indian that I even attempted speaking in Hindi to the few I saw panhandling tourists near the Paris Opera. A stop mutation in the LTBP2 gene has been linked to developmental glaucoma in a class of Roma. Ali et al. (2009 Am. J. Hum. Genet. 84 664–671) found that this stop mutation, along with 14 flanking SNPs, was shared …