Particular Mal de Meleda Phenotypes in Tunisia and Mutations Founder Effect in the Mediterranean Region
Particular Mal de Meleda Phenotypes in Tunisia and Mutations Founder Effect in the Mediterranean Region
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DOI：
10.1155/2013/206803
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发表时间：
2013-01-01
影响因子：
--
通讯作者：
Benmously, Rym
中科院分区：
文献类型：
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作者：
Bchetnia, Mbarka;Laroussi, Nadia;Benmously, Rym
Mal de Meleda(MDM)是一种罕见的常染色体隐性掌足部角化病。它的特征是手掌和脚掌的红斑和角化过度，逐渐延伸到手脚的背部表面。它是由哺乳动物分泌的Ly-6/uPAR相关蛋白1(slurp-1)的slurp-1基因突变引起的。我们通过SURLP-1基因的直接测序进行突变分析，以确定三个不同的受侵袭性掌跖角化病影响的家系(MDM-12、MDM-13和MDM-14)的遗传缺陷。临床表现多种多样，从明显的角化过度到透明的角化过度。我们在MDM-12和MDM-13两个家族中都发现了slurp-1基因的82delT移码突变，在MDM-14家族中发现了错义突变p.Cys99Tyr。到目前为止，82delT变异是世界上最常见的MDM原因，它有利于反复发生的分子缺陷。P.Cys99Tyr变异仅在突尼斯家庭中描述，这证明创始人效应突变可能起源于突尼斯。我们的患者表现为非常严重到相对较轻的表型，包括一名患者在角化过度区域观察到的多个角化溶解凹陷，这是以前没有报道的。表型变异可能反映了附加因素对疾病特性的影响。这份报告进一步扩大了地中海人群中与SLURP1突变相关的临床表型的范围。
Mal de Meleda (MDM) is a rare, autosomal recessive form of palmoplantar keratoderma. It is characterized by erythema and hyperkeratosis of the palms and soles that progressively extend to the dorsal surface of the hands and feet. It is caused by mutations in SLURP-1 gene encoding for secreted mammalian Ly-6/uPAR-related protein 1 (SLURP-1). We performed mutational analysis by direct sequencing of SLURP-1 gene in order to identify the genetic defect in three unrelated families (families MDM-12, MDM-13, and MDM-14) variably affected with transgressive palmoplantar keratoderma. A spectrum of clinical presentations with variable features has been observed from the pronounced to the transparent hyperkeratosis. We identified the 82delT frame shift mutation in the SLURP-1 gene in both families MDM-12 and MDM-13 and the missense variation p.Cys99Tyr in family MDM-14. To date, the 82delT variation is the most frequent cause of MDM in the world which is in favour of a recurrent molecular defect. The p.Cys99Tyr variation is only described in Tunisian families making evidence of founder effect mutation of likely Tunisian origin. Our patients presented with very severe to relatively mild phenotypes, including multiple keratolytic pits observed for one patient in the hyperkeratotic area which was not previously reported. The phenotypic variability may reflect the influence of additional factors on disease characteristics. This report further expands the spectrum of clinical phenotypes associated with mutations in SLURP1 in the Mediterranean population.