One novel and two recurrent missense DKC1 mutations in patients with dyskeratosis congenita (DKC).
One novel and two recurrent missense DKC1 mutations in patients with dyskeratosis congenita (DKC).
复制标题
先天性角化不良 (DKC) 患者中的一种新的错义 DKC1 突变和两种复发性错义 DKC1 突变。
作者：
N. Heiss;A. Mégarbané;S. Klauck;F. Kreuz;E. Makhoul;F. Majewski;A. Poustka
X 连锁先天性角化不良 (DKC) 是一种进行性多系统疾病，对细胞更新率高的组织（如皮肤、粘膜和血液）影响最严重。大多数患者死于骨髓衰竭，但死于各种癌症和肺部疾病的机会也很高。 DKC 主要是由与 Xq28 相关的 DKC1 基因的错义突变引起的。一些临床特征让人想起过早衰老，这与最近的迹象一致，即 DKC 可能是一种端粒维持障碍。各种异常的类型、严重程度和发病年龄存在很大差异。随着霍耶拉尔-赫里达森综合征 (HHS) 患者除了早发性全血细胞减少症之外还表现出严重的神经系统问题，并且还携带 DKC1 基因突变，这一发现增加了人们对这一点的认识。由于这些原因，再加上突变的范围，表型-基因型相关性和准确的预后评估是不可能的。为了补充现有数据，我们在此报告三例新的 DKC 病例及其突变。其中之一是外显子 3 (K43E) 的新突变。另外两个代表外显子 11 (A353V) 中频繁出现的突变和外显子 3 (T49M) 中出现频率较低的突变。
X-linked dyskeratosis congenita (DKC) is a progressive multisystem disorder most severely affecting tissues with a high cellular turnover such as skin, mucous membranes, and blood. Most patients die of bone marrow failure, although the chances of succumbing to various types of cancer and pulmonary disease are also high. DKC is caused predominantly by missense mutations in the DKC1 gene linked to Xq28. Some of the clinical features are reminiscent of premature ageing and this agrees with recent indications that DKC could be a telomere maintenance disorder. There is considerable variability in the type, severity, and age at onset of the various anomalies. Recognition of this has increased with the finding that patients with Hoyeraal-Hreidarsson syndrome (HHS) who exhibit severe neurological problems in addition to early-onset pancytopenia, also bear mutations in the DKC1 gene. For these reasons, and compounded by the range of mutations, phenotype-genotype correlations and accurate assessments of prognosis have not been possible. To complement the present data, we here report on three new cases of DKC and their mutations. One is a novel mutation in the exon 3 (K43E). The other two represent a frequently recurring mutation in exon 11 (A353V) and a less frequently recurring mutation in the exon 3 (T49M).