Strict sun protection results in minimal skin changes in a patient with xeroderma pigmentosum and a novel c.2009delG mutation in XPD (ERCC2)
Strict sun protection results in minimal skin changes in a patient with xeroderma pigmentosum and a novel c.2009delG mutation in XPD (ERCC2)
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DOI：
10.1111/j.1600-0625.2008.00763.x
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发表时间：
2009-01-01
影响因子：
3.6
通讯作者：
Kraemer, Kenneth H.
中科院分区：
文献类型：
--
作者：
Emmert, Steffen;Ueda, Takahiro;Kraemer, Kenneth H.
我们研究了一个16岁的男孩（XP 2GO）与着色性干皮病（XP）和进行性神经症状的临床，分子和遗传特征。父母不是血亲。增加的阳光敏感性导致XP的诊断在2岁和严格的紫外线防护方案实施。除了复发性结膜炎和双侧翼状胬肉外，他的嘴唇上只有轻微的雀斑。他表现出缺乏深腱反射，进行性感音神经性耳聋和进行性智力迟钝。MRI显示弥漫性额叶脑萎缩和脑室扩张。没有脊髓硫营养不良（偏光显微镜下可见虎尾巴带状的脆性毛发）或Cockayne综合征（恶病质性侏儒症、白内障、色素性视网膜病和痉挛）的症状。XP 2GO成纤维细胞显示UV后细胞存活率降低（D-37 = 3.8 J/m2），核苷酸切除修复减少，XPD mRNA表达减少，XPD蛋白水平检测不到。XP 2GO中XPD基因的突变分析揭示了两种不同的突变：已知与XP相关的常见p.Arg683Trp氨基酸改变（c.2047C > T）和新的移码突变c.2009delG（p.Gly670Alafs*39）。后一种突变可能表现为无效等位基因。虽然不能预防神经退行性变，但早期诊断和严格的防晒措施可能会导致XP患者出现最小的皮肤病，而不会导致癌症。
We examined the clinical, molecular and genetic features of a 16-year-old boy (XP2GO) with xeroderma pigmentosum (XP) and progressive neurological symptoms. The parents are not consanguineous. Increased sun sensitivity led to the diagnosis of XP at 2 years of age and a strict UV protection scheme was implemented. Besides recurrent conjunctivitis and bilateral pterygium, only mild freckling was present on his lips. He shows absent deep tendon reflexes, progressive sensorineural deafness and progressive mental retardation. MRI shows diffuse frontal cerebral atrophy and dilated ventricles. Symptoms of trichothiodystrophy (brittle hair with a tiger-tail banding pattern on polarized microscopy) or Cockayne syndrome (cachectic dwarfism, cataracts, pigmentary retinopathy and spasticity) were absent. XP2GO fibroblasts showed reduced post-UV cell survival (D-37 = 3.8 J/m(2)), reduced nucleotide excision repair, reduced expression of XPD mRNA and an undetectable level of XPD protein. Mutational analysis of the XPD gene in XP2GO revealed two different mutations: a common p.Arg683Trp amino acid change (c.2047C > T) known to be associated with XP and a novel frameshift mutation c.2009delG (p.Gly670Alafs*39). The latter mutation potentially behaves as a null allele. While not preventing neurological degeneration, early diagnosis and rigorous sun protection can result in minimal skin disease without cancer in XP patients.