背景:常染色体隐性遗传先天性鱼鳞病(ARCI)是一组异质性的罕见角质化疾病。迄今为止,已鉴定出超过13个致病基因。然而,泰国缺乏包括基因型-表型相关性在内的临床和分子特征数据.
目的:我们收集了2011年至2021年在皮肤科研究所诊断为非综合征性ARCI和综合征性隐性先天性鱼鳞病的病例,并使用下一代测序进行了基因检测,并评估了临床细节。
方法:基线人口统计数据,出生史,家族史,出生时的皮肤表现,当前的皮肤表现,合并症,并评估对治疗的反应。使用与先天性鱼鳞病相关的45个基因的靶向基因测序来筛选DNA的突变。
结果:共分析了33例患者,平均年龄为23.8±13.9岁。先天性鱼鳞状红皮病(CIE)最常见(60.6%),其次是层状鱼鳞病(18.2%),自我改善的先天性鱼鳞病(6.1%),Netherton综合征(6.1%),鱼鳞病早产儿综合征(3%),干燥-拉尔森综合征(3%)和泳衣鱼鳞病(3%)。在我们的队列中发现了八个基因与致病变异如下:ABCA1242.4%(14/33),NIPAL424.2%(8/33),TGM115.2%(5/33),SPINK56.1%(2/33),ALDH3A23%(1/33),SLC27A43%(1/33),CYP4F223%(1/33),ST143%(1/33)。临床上,本研究中79%的ABCA12致病变异患者患有E,79%的w具有新的双等位基因致病性复合杂合变体,而21%有纯合错义变异。
结论:这是首次在泰国队列中描述ARCI的临床和分子发现的研究。我们的发现证明了这些疾病的临床谱,并扩大了东南亚人群的分子发现。
BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a heterogenous group of rare keratinization disorders. To date, more than 13 causative genes have been identified. However, data on clinical and molecular characteristics including genotype-phenotype correlation are lacking in Thailand.
OBJECTIVE: We collected cases diagnosed with non-syndromic ARCI and syndromic recessive congenital ichthyosis at the Institute of Dermatology from 2011 to 2021 and performed genetic testing with next-generation sequencing and assessed clinical details.
METHODS: Baseline demographic data, birth history, family history, skin manifestations at birth, current cutaneous manifestations, comorbidities, and response to treatments were assessed. DNA was screened for mutations using targeted gene sequencing of 45 genes related to congenital ichthyosis.
RESULTS: A total of 33 patients were analyzed with an average age of 23.8 ± 13.9 years. Congenital ichthyosiform erythroderma (CIE) was most common (60.6%), followed by lamellar ichthyosis (18.2%), self-improving congenital ichthyosis (6.1%), Netherton syndrome (6.1%), ichthyosis prematurity syndrome (3%), Sjögren-Larsson syndrome (3%) and bathing suit ichthyosis (3%). Eight genes were found with pathogenic variants in our cohort as follows: ABCA12 42.4% (14/33), NIPAL4 24.2% (8/33), TGM1 15.2% (5/33), SPINK5 6.1% (2/33), ALDH3A2 3% (1/33), SLC27A4 3% (1/33), CYP4F22 3% (1/33), and ST14 3% (1/33). Clinically, 79% of patients with ABCA12 pathogenic variants in this study had CIE, 79% of w had novel biallelic pathogenic compound heterozygous variants, whereas 21% had homozygous missense variants.
CONCLUSIONS: This is the first study to describe clinical and molecular findings of ARCI in a cohort from Thailand. Our findings demonstrate the clinical spectrum of the diseases and expand the molecular findings in a Southeast Asian population.