Vörner type palmoplantar keratoderma: novel KRT9 mutation associated with knuckle pad‐like lesions and recurrent mutation causing digital mutilation
Vörner type palmoplantar keratoderma: novel KRT9 mutation associated with knuckle pad‐like lesions and recurrent mutation causing digital mutilation
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DOI：
10.1111/j.1365-2133.2011.10317.x
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发表时间：
2011-07
影响因子：
10.3
通讯作者：
N. Umegaki;H. Nakano;Katuto Tamai;Yoshihiko Mitsuhashi;E. Akasaka;D. Sawamura;Ichiro Katayama
中科院分区：
文献类型：
--
作者：
N. Umegaki;H. Nakano;Katuto Tamai;Yoshihiko Mitsuhashi;E. Akasaka;D. Sawamura;Ichiro Katayama
Vörner型表皮性掌跖角化病（EPPK，OMIM 144200）是一种常染色体显性遗传性皮肤病，由角蛋白9基因（KRT 9）突变引起，角蛋白1基因很少突变。这种情况的特点是弥漫性的黄色增厚的皮肤的手掌和脚底，急剧抵消的边缘。组织学上，EPPK表现为表皮增生性角化病的特征。本报告涉及两个日本EPPK家族与相关的特征性皮肤表现：指关节垫样病变与一种新的无义KRT 9突变和数字切割引起的复发KRT 9突变。家系1的先证者是一名12岁的日本女孩，出生后不久即出现手掌和脚掌角化过度（图1a）。在手部远节指骨背侧观察到肥大斑块伴红斑（图1a，下图）。在脚趾上观察到类似的病变，但程度较轻（未显示）。没有其他家庭成员受到影响。组织学检查显示表皮角化过度伴大的不规则透明角化颗粒和上棘层和颗粒层角质形成细胞空泡化（未显示）。家族2的先证者是一名58岁的日本女性，表现为出生后不久出现的手掌和脚掌角化过度。她的父亲和姐姐有类似的过度角化皮肤变化。在她生命的第二个十年里，先证者第一次注意到第五个脚趾感到轻度收缩。从那时起，收缩逐渐进展，伴随着第五脚趾的麻木。当她50岁时，收缩的第五脚趾自发脱离，没有创伤性病因（图1b，箭头）。观察到先证者手指关节轻微收缩，尤其是中间指间关节（图1b，箭头）。其他受影响的人没有表现出任何收缩性变化，在他们的手指或脚趾，也没有任何指关节垫样病变。组织学检查表明表皮炎性角化过度伴颗粒层空泡化（未显示）。从先证者及其家族成员中提取的基因组DNA样本进行突变分析。在先证者中，通过聚合酶链反应（PCR）扩增所有KRT 9外显子及其侧翼外显子/内含子连接，并将PCR产物直接测序。突变分析显示，在家族1的先证者中，KRT 9外显子6的核苷酸位置1282（c.1282C>T）处存在C到T的转换（图2a），但在健康父母中没有，
Epidermolytic palmoplantar keratoderma, Vörner type (EPPK, OMIM 144200) is an autosomal dominantly inherited skin disease caused by mutations in the keratin 9 gene (KRT9) and rarely in the keratin 1 gene. This condition is characterized by diffuse yellow thickening of the skin of the palms and soles, sharply offset by erythematous margins. Histopathologically, EPPK presents the characteristic features of epidermolytic hyperkeratosis. This report concerns two Japanese EPPK families with associated characteristic cutaneous manifestations: knuckle pad-like lesions associated with a novel nonsense KRT9 mutation and digital mutilation caused by a recurrent KRT9 mutation. The proband of family 1 was a 12-year-old Japanese girl presenting with hyperkeratosis of palms and soles since soon after birth (Fig. 1a). Hypertrophic plaques with erythema were noted on the dorsal aspects of the distal phalanges of the hands (Fig. 1a, lower panel). Similar lesions, but to a lesser extent, were seen on the toes (not shown). No other family members were affected. Histopathology showed epidermolytic hyperkeratosis with large irregular keratohyaline granules and vacuolization of keratinocytes in the upper spinous and granular layers (not shown). The proband of family 2 was a 58-year-old Japanese woman presenting with hyperkeratosis of palms and soles that developed soon after birth. Her father and elder sister had similar hyperkeratotic skin changes. In the second decade of her life, t‘he proband first noted that the fifth toes felt mildly constricted. Since then, the constriction gradually progressed with accompanying numbness of the fifth toes. When she was 50 years old, the constricted fifth toes became detached spontaneously with no traumatic aetiology (Fig. 1b, arrows). Slight constriction of the finger joints of the proband was observed, especially of the middle interphalangeal joints (Fig. 1b, arrowheads). The other affected individuals did not show any constrictive changes in their fingers or toes nor any knuckle pad-like lesions. Histopathology indicated epidermolytic hyperkeratosis with vacuolization of the granular layer (not shown). Genomic DNA samples extracted from the probands and their family members were subjected to mutation analyses. In the probands, all the KRT9 exons and their flanking exon ⁄ intron junctions were amplified by polymerase chain reaction (PCR) and the PCR products were directly sequenced. Mutational analysis revealed a C-to-T transition at nucleotide position 1282 (c.1282C>T) in exon 6 of KRT9 in the proband of family 1 (Fig. 2a), but not in the healthy parents, suggestBJD British Journal of Dermatology