Courdier Cécile, Michaud Vincent, Diallo Modibo, Plaisant Claudio, Lasseaux Eulalie, Helot Isabelle, Philippe Elodie, Vrielynck Els, Willems Marjolaine, Arveiler Benoit
Service de Génétique Médicale, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
Laboratoire Maladies Rares, Génétique et Métabolisme, Bordeaux University INSERM U1211, Bordeaux, France.
Eur J Hum Genet. 2025 Mar;33(3):383-386. doi: 10.1038/s41431-024-01779-5. Epub 2025 Jan 14.
Pigmentation is orchestrated by hundreds of genes involved in cellular functions going from early developmental fate of pigment cells to melanin synthesis. The Two Pore Channel 2 (TPC2) a Ca2+ and Na+ channel acidifies melanosomal pH and thus inhibits pigmentation. A young patient was recently reported with generalized hypopigmentation but uneventful ocular examination, caused by the de novo heterozygous TPCN2 variant c.628C>T;p.Arg210Cys that constitutively activates TPC2. Here we report a young patient with the same de novo variant presenting with generalized hypopigmentation, and ophthalmologic features including low grade retinal hypopigmentation and foveal hypoplasia, photophobia, mild hypermetropia, and astigmatism, which are features of albinism. Skin fragility and episodes of fever with diarrhea and fatigue were also observed. This extends the phenotype of patients with TPCN2 variants, warranting further investigations in patients with alterations of this gene, and raises the question whether TPCN2 might be considered as an albinism gene.
色素沉着由数百个参与细胞功能的基因调控，这些功能从色素细胞的早期发育命运到黑色素合成。双孔通道2（TPC2），一种钙和钠通道，可酸化黑素小体的pH值，从而抑制色素沉着。最近报道了一名年轻患者，其因从头杂合TPCN2变体c.628C>T;p.Arg210Cys导致全身性色素减退，但眼部检查正常，该变体可组成性激活TPC2。在此，我们报告一名患有相同从头变体的年轻患者，其表现为全身性色素减退，以及包括低度视网膜色素减退和黄斑发育不全、畏光、轻度远视和散光在内的眼科特征，这些都是白化病的特征。还观察到皮肤脆弱以及伴有腹泻和疲劳的发热发作。这扩展了TPCN2变体患者的表型，有必要对该基因改变的患者进行进一步研究，并提出了TPCN2是否可被视为白化病基因的问题。
