识别和描述的八个小说SMPD1突变导致类型A和B尼曼氏病。
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Desnick JP,金正日J,他X,瓦瑟斯坦MP, Simonaro厘米,Schuchman呃
识别和描述的八个小说SMPD1突变导致类型A和B尼曼氏病。
摩尔地中海。2010 Jul-Aug; 16(7 - 8): 316 - 21所示。doi: 10.2119 / molmed.2010.00017。Epub 2010年4月6日。
- PubMed ID
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20386867 (在PubMed]
- 文摘
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A型和B型尼曼氏病(NPD)由于酸性鞘磷脂酶的缺乏活动(ASM),由于突变鞘磷脂磷酸二酯酶1基因(SMPD1)。这里我们报告识别、描述和八个小说突变的基因型和表现型相关性在六个无关的NPD的病人。这些变异包括七个错义突变:c。631 t > C (p.W211R), C。757 g > C (p.D253H), C。940 g > A (p.V314M), c。1280 > G (p.H427R), c。1564 > G (p.N522S), c。1575 g > C (p.Q525H)和C。> 1729 G (p.H577R),一种新颖的移码突变,c。1657年delaccgcct (fsT553)。每一个错义突变是在293 t或COS-7细胞表达;突变体酶p。W211R, p。D253H, p。H427R和p。H577R有<表达野生型活动的1%,而p。V314M, p。N522S and p.Q525H had 21.7%, 10.1% and 64% of expressed wild-type activity, respectively. The c.1564A>G mutation obliterated a known N-glycosylation site and its p.N522S mutant enzyme had ~10% of expressed wild-type activity. Western blot analysis revealed that each mutant protein was expressed at near wild-type amounts, despite their differences in residual activity. The novel seven-base deletion occurred at codon 553, leading to a premature truncation after residue 609. The expression studies predicted the clinical phenotypes of the six patients: two type A patients had genotypes with only type A alleles [c.631T>C (p.W211R), c.757G>C (p.D253H) and c.1729A>G (p.H577R)], and the other four type B disease patients had at least one neuroprotective mutant type B allele [c.940G>A (p.V314M), c.1280A>G (p.H427R), c.1564A>G (p.N522S) and c.1575G>C (p.Q525H)] that expressed >5% residual ASM activity. Thus, these new mutations provide novel genotype/phenotype correlations and further document the genetic heterogeneity in types A and B NPD.