Al Hawsawi Khalid, Al Jabri Mazin, Dajam Mazen S, Almahdi Bashaer, Alhawsawi Waseem K, Abbas Safdar, Al Tuwaijri Abeer, Umair Muhammad, Alfadhel Majid, Al-Khenaizan Sultan
Dermatology Department, King Abdulaziz Hospital, Makkah, Saudi Arabia.
Dermatology Department, Hera General Hospital, Makkah, Saudi Arabia.
Front Genet. 2022 Aug 17;13:994509. doi: 10.3389/fgene.2022.994509. eCollection 2022.
Hypotrichosis with Recurrent Skin Vesicles (HYPTSV) is an extremely rare condition, having autosomal recessive inheritance. Here in we report a 4-years- old Saudi boy who presented with a history of recurrent skin blisters that are localized to the extremities and hypotrichosis since birth. The present study describes a consanguineous Saudi family segregating HYPTSV in an autosomal recessive fashion. A single proband (II-1) exhibited features such as diffused non-scarring alopecia on the scalp, intraepidermal blister, post-inflammatory hyperpigmented macules, and follicular hyperkeratosis. DNA of the index was subjected to whole-genome sequencing (WGS). Furthermore, 3D protein modeling was performed for the mutated and normal protein. WGS revealed a novel bi-allelic missense variant (c.154G>C; p. Val52Leu) in the gene, which segregated perfectly using Sanger sequencing. In addition, 3D protein modeling revealed a substantial change in the mutated DSC3 protein as compared to the normal DSC3 protein. This is the 3rd novel variant reported in the gene associated with the HYPTSV phenotype. This report further strengthens the evidence that bi-allelic variants in the cause severe HYPTSV in humans.
伴有复发性皮肤水疱的少毛症（HYPTSV）是一种极为罕见的疾病，呈常染色体隐性遗传。在此，我们报告一名4岁的沙特男孩，自出生以来就有反复出现的局限性于四肢的皮肤水疱病史及少毛症。本研究描述了一个沙特近亲家庭，该家庭以常染色体隐性方式遗传HYPTSV。一名先证者（II-1）表现出头皮弥漫性非瘢痕性脱发、表皮内水疱、炎症后色素沉着斑和毛囊角化过度等特征。对先证者的DNA进行了全基因组测序（WGS）。此外，对突变蛋白和正常蛋白进行了三维蛋白质建模。WGS在该基因中发现了一个新的双等位基因错义变异（c.154G>C；p.Val52Leu），通过桑格测序完美分离。此外，三维蛋白质建模显示，与正常DSC3蛋白相比，突变的DSC3蛋白有显著变化。这是该基因中报道的与HYPTSV表型相关的第3个新变异。本报告进一步强化了双等位基因变异导致人类严重HYPTSV的证据。
