Piard Juliette, Holder-Espinasse Muriel, Aral Bernard, Gigot Nadège, Rio Marlène, Tardieu Marc, Puzenat Eve, Goldenberg Alice, Toutain Annick, Franques Jerôme, MacDermot Kay, Bessis Didier, Boute Odile, Callier Patrick, Gueneau Lucie, Huet Frédéric, Vabres Pierre, Catteau Benoît, Faivre Laurence, Thauvin-Robinet Christel
Centre de Génétique Humaine, CHU Besançon, France.
Eur J Med Genet. 2012 Jan;55(1):8-11. doi: 10.1016/j.ejmg.2011.07.004. Epub 2011 Aug 18.
Poikiloderma occurs in a number of hereditary syndromes, the best known of which is Rothmund-Thomson syndrome (RTS). Differential diagnoses include Dyskeratosis Congenita (DC) with high genetic heterogeneity and Clericuzio-type Poikiloderma with Neutropenia (CPN) due to mutations in the C16orf57 gene. Mutations in the RECQL4 gene are only observed in two thirds of RTS patients. In this study, 10 patients referred for syndromic poikiloderma and negative for RECQL4 sequencing analysis were investigated for C16orf57 mutations. Two C16orf57 heterozygous nonsense mutations (p.W81X and p.Y89X) were identified in a 5-year-old female child presenting with generalized poikiloderma, dental dysplasia, gingivitis, nail dystrophy, palmoplantar keratoderma and pachyonychia of the great toenails. Previously undetected and silent neutropenia was evidenced after C16orf57 molecular analysis. Neutropenia was absent in the C16orf57-negative patients. This report confirms that neutrophil count should be performed in all patients with poikiloderma to target the C16orf57 gene sequencing analysis, prior to RECQL4 analysis.
皮肤异色症见于多种遗传性综合征，其中最著名的是罗思蒙德-汤姆森综合征（RTS）。鉴别诊断包括具有高度遗传异质性的先天性角化不良（DC）和由于C16orf57基因突变导致的伴中性粒细胞减少的克莱里库齐奥型皮肤异色症（CPN）。RECQL4基因突变仅在三分之二的RTS患者中观察到。在本研究中，对10例因综合征性皮肤异色症转诊且RECQL4测序分析为阴性的患者进行了C16orf57基因突变检测。在一名患有全身性皮肤异色症、牙齿发育异常、牙龈炎、指甲营养不良、掌跖角化病和大脚趾甲甲肥厚的5岁女童中鉴定出两个C16orf57杂合无义突变（p.W81X和p.Y89X）。C16orf57分子分析后证实存在先前未检测到的无症状中性粒细胞减少。C16orf57基因阴性的患者不存在中性粒细胞减少。本报告证实，在对所有皮肤异色症患者进行RECQL4分析之前，应进行中性粒细胞计数，以作为C16orf57基因测序分析的靶点。
