Supplementary Material for: Novel compound heterozygous variants of DSP causing skin fragility-woolly hair syndrome: a rare case report and literature review

Introduction: Desmoplakin is constitutive component of desmosome which plays a critical part in keratinocyte adhesion. Skin fragility-woolly hair syndrome (SFWHS) is a very rare autosomal recessive disorder caused by variants in desmoplakin (DSP). Case Presentation: Herein, we described a 2-year-old Chinese boy who presented with palmoplantar keratoderma, short curly hair and thickening of nails since birth. Histopathological examination showed hyperkeratosis, acanthosis, hypergranulosis and prominent intercellular fissures. Two heterozygous variants in exon 24 of DSP, c.7642C>T (p.R2548X) and c.6449delC (p.R2151Gfs*3), were identified by whole-exome sequencing and further proven to be a novel compound heterozygous variant by Sanger sequencing. Both variants have not been identified and reported previously. Discussion/Conclusion: To the best of our knowledge, this is the second case of SFWHS with compound heterozygous variants in Chinese population. This case adds new variant spectrum in DSP of SFWHS and highlights the need for genetic testing understanding in patients with characteristic cutaneous findings.引言：桥粒斑蛋白（Desmoplakin, DSP）是桥粒（desmosome）的组成型成分，在角质形成细胞黏附过程中发挥关键作用。皮肤脆性-羊毛状发综合征（Skin fragility-woolly hair syndrome, SFWHS）是一种极为罕见的常染色体隐性遗传病，由桥粒斑蛋白基因变异所致。 病例报告：本文报道一例2岁男性中国患儿，自出生起即出现掌跖角化病、短卷发及指甲增厚症状。组织病理学检查可见角化过度、棘层肥厚、颗粒层增厚及显著的细胞间裂隙。通过全外显子测序，在DSP基因第24号外显子中检出两处杂合变异：c.7642C>T（p.R2548X）与c.6449delC（p.R2151Gfs*3）；经桑格测序验证，上述变异为新型复合杂合变异，且此前均无相关发现与报道记录。 讨论与结论：据我们所知，本研究为中国人群中第二例携带复合杂合变异的SFWHS病例。本病例丰富了SFWHS患者DSP基因的变异谱，并强调了针对具有特征性皮肤表现的患者开展遗传检测的必要性。