Steiner Carlos Eduardo, Puzzi Maria Beatriz, Marques-de-Faria Antonia Paula, de Oliveira Sobrinho Ruy Pires, Gil-da-Silva-Lopes Vera Lúcia, Moreno Carolina Araújo
Departamento de Genética Médica e Medicina Genômica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), Campinas 13083-888, SP, Brazil.
Disciplina de Dermatologia, Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), Campinas 13083-888, SP, Brazil.
Genes (Basel). 2025 Apr 29;16(5):522. doi: 10.3390/genes16050522.
BACKGROUND/OBJECTIVES: Genodermatoses are genetic conditions with clinical symptoms manifesting in the skin and adjoining tissues, individually rare but comprising a large and heterogeneous group of disorders that represents 15% of genetic diseases. This article discusses the results of individuals with genodermatoses from a reference center for rare diseases studied through whole genome sequencing conducted by the Brazilian Rare Genomes Project between 2021 and 2023.
A retrospective case series with data comprising sex, age at first assessment in the hospital, family history, clinical findings, and molecular results.
Excluding neurofibromatosis type 1, Ehlers-Danlos syndrome and RASopathies are discussed elsewhere. Diagnoses in this work comprised ectodermal dysplasias ( = 6), ichthyosis ( = 4), albinism ( = 4), tuberous sclerosis complex ( = 4), and incontinentia pigmenti ( = 3), in addition to 11 others with individual rare conditions. The sex ratio was 17:16 (M:F), consanguinity was present in 6/33 (18%), and the age at the first evaluation ranged from neonatal to 26 years (median 13.65 years). Negative results were 3/33 (9%), novel variants were 17/41 (41.4%), and 7/30 (23%) presented initially with a double molecular diagnosis, three confirming composed phenotypes.
Besides reporting 17 novel variants in 14 genes (, , , , , , , , , , , , , and ), the study also identified three atypical clinical presentations due to dual diagnoses, and the c.454C>T variant in the gene, previously reported only in dogs, was, for the first time, confirmed as causative for ichthyosis in humans.
背景/目的：遗传性皮肤病是一类遗传性疾病，其临床症状表现在皮肤及相邻组织，虽个体发病率低，但构成了一个庞大且异质性的疾病群体，占遗传性疾病的15%。本文讨论了2021年至2023年期间巴西罕见基因组计划通过全基因组测序对一家罕见病参考中心的遗传性皮肤病患者的研究结果。
一项回顾性病例系列研究，数据包括性别、首次入院评估年龄、家族史、临床发现和分子检测结果。
1型神经纤维瘤病、埃勒斯-当洛综合征和RAS病不在本文讨论范围内。本研究中的诊断包括外胚层发育不良（n = 6）、鱼鳞病（n = 4）、白化病（n = 4）、结节性硬化症（n = 4）、色素失禁症（n = 3），此外还有11例患有其他罕见的个体疾病。性别比为17:16（男:女），6/33（18%）存在近亲结婚情况，首次评估年龄从新生儿到26岁不等（中位数13.65岁）。阴性结果为3/33（9%），新变异为17/41（41.4%），7/30（23%）最初表现为双重分子诊断，其中3例确诊为复合型表型。
除了报告14个基因（、、、、、、、、、、、、和）中的17个新变异外，该研究还发现了3例因双重诊断导致的非典型临床表现，并且首次证实基因中c.454C>T变异是人类鱼鳞病的致病原因，该变异此前仅在犬类中报道过。
