Bchetnia Mbarka, Merdassi Ahlem, Charfeddine Cherine, Mgaieth Fatma, Kassar Selma, Ouechtati Farah, Chouchene Ibtissem, Boussen Hamouda, Mokni Mourad, Osman Amel Dhahri-Ben, Boubaker Med Samir, Abdelhak Sonia, Elmatri Leila
Molecular Investigation of Genetic Orphan Diseases Research Unit, Institut Pasteur de Tunis, Tunis, Tunisia.
J Med Case Rep. 2010 Apr 20;4:108. doi: 10.1186/1752-1947-4-108.
Mal de Meleda is a rare form of palmoplantar keratoderma, with autosomal recessive transmission. It is characterized by diffuse erythema and hyperkeratosis of the palms and soles. Recently, mutations in the ARS (component B) gene (ARS, MIM: 606119) on chromosome 8q24.3 have been identified in families with this disorder. Congenital cataract is a visual disease that may interfere with sharp imaging of the retina. Mutations in the heat-shock transcription factor 4 gene (HSF4; MIM: 602438) may result in both autosomal dominant and autosomal recessive congenital cataracts.
A Tunisian family with two female siblings aged 45 and 30 years, presented with a clinical association of mal de Meleda and congenital cataract. The two patients exhibited diffuse palmoplantar keratodermas. One of them presented with a total posterior subcapsular cataract and had a best corrected visual acuity at 1/20 in the left eye and with the right eye was only able to count fingers at a distance of one foot. The other woman had a slight posterior subcapsular lenticular opacity and her best corrected visual acuity was 8/10 in the right eye and with her left eye she was only able to count fingers at a distance of one foot. A mutational analysis of their ARS gene revealed the presence of the homozygous missense mutation C99Y and two single nucleotide polymorphisms (-55G>C and -60G>C). The splice mutation (c.1327+4A-G) within intron 12 of the HSF4 gene, which has been previously described in Tunisian families with congenital cataract, was not found in the two probands within this family.
To the best of our knowledge, such original clinical association has not been reported previously. The association of these two autosomal recessive diseases might have occurred in this family due to a high degree of inbreeding. The C99Y mutation may be specific to the Tunisian population as it has been exclusively reported so far in only three Tunisian families with mal de Meleda.
梅勒达病是掌跖角化病的一种罕见形式，呈常染色体隐性遗传。其特征为手掌和足底弥漫性红斑及角化过度。最近，在患有这种疾病的家族中，已在8号染色体q24.3上的ARS（组分B）基因（ARS，MIM：606119）中发现了突变。先天性白内障是一种可能会干扰视网膜清晰成像的视觉疾病。热休克转录因子4基因（HSF4；MIM：602438）中的突变可能导致常染色体显性和常染色体隐性先天性白内障。
一个突尼斯家庭，有两名分别为45岁和30岁的女性同胞，表现出梅勒达病与先天性白内障的临床关联。这两名患者均表现出弥漫性掌跖角化病。其中一人患有完全性后囊下白内障，左眼最佳矫正视力为1/20，右眼仅能在1英尺远的距离数手指。另一名女性有轻微的后囊下晶状体混浊，右眼最佳矫正视力为8/10，左眼仅能在1英尺远的距离数手指。对她们的ARS基因进行突变分析发现存在纯合错义突变C99Y以及两个单核苷酸多态性（-55G>C和-60G>C）。在该家族的两名先证者中未发现HSF4基因第12内含子中的剪接突变（c.1327 + 4A - G），此前在突尼斯先天性白内障家族中曾描述过该突变。
据我们所知，此前尚未报道过这种独特的临床关联。这两种常染色体隐性疾病在该家族中的关联可能是由于高度近亲繁殖所致。C99Y突变可能是突尼斯人群特有的，因为迄今为止仅在三个患有梅勒达病的突尼斯家族中报告过。
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