常染色体隐性先天性鱼鳞病横断面研究:74 名意大利患者的基因型与疾病严重程度、表型和超微结构特征的关系。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
A. Diociaiuti, M. Corbeddu, Sabrina Rossi, E. Pisaneschi, C. Cesario, A. Condorelli, Tonia Samela, S. Giancristoforo, Adriano Angioni, Giovanna Zambruno, Antonio Novelli, Rita Alaggio, Damiano Abeni, M. El Hachem
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Skin ultrastructural findings were reviewed.\n\n\nRESULTS\nSeventy-four consecutive patients (mean age 11.0 years, range 0.1-48.8) affected with lamellar ichthyosis (50/74, 67.5%), congenital ichthyosiform erythroderma (18/74, 24.3%), harlequin ichthyosis (two/74, 2.7%), and other minor ARCI subtypes (four/74, 5.4%) were enrolled. Mutated genes were: TGM1 in 18/74 (24.3%) patients, ALOX12B in 18/74 (24.3%), CYP4F22 in 12/74 (16.2%), ABCA12 in nine/74 (12.2%), ALOXE3 in seven/74 (9.5%), NIPAL4 in seven/74 (9.5%), and CERS3, PNPLA1 and SDR9C7 in one patient each (1.4%). Twenty-five previously undescribed mutations in the different ARCI causative genes, as well as two microduplications in TGM1, and two microdeletions in CYP4F22 and NIPAL4 were identified. The mean ichthyosis severity score in TGM1 and ABCA12-mutated patients was significantly higher than in all other mutated genes, while the lowest score was observed in CYP4F22-mutated patients. Alopecia, ectropion, and eclabium were significantly associated with TGM1 and ABCA12 mutations, and large, thick and brownish scales with TGM1 mutations. Among specific phenotypic features, psoriasis-like lesions as well as a trunk reticulate scale pattern and striated keratoderma were present in NIPAL4-mutated patients. Ultrastructural data available for 56 patients showed a 100% specificity of cholesterol clefts for TGM1-mutated cases, and revealed abnormal lamellar bodies in SDR9C7 and CERS3 patients.\n\n\nCONCLUSION\nOur study expands the phenotypic and genetic characterization of ARCI by the description of statistically significant associations between disease severity, specific clinical signs, and different mutated genes. 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引用次数: 0

摘要

背景常染色体隐性遗传先天性鱼鳞病(ARCI)是一组临床上异质性的角化障碍性疾病,其特征是由于至少 12 个基因的突变导致全身皮肤脱屑。我们的研究旨在评估 ARCI 患者的疾病严重程度、表型和超微结构特征,并评价它们与遗传结果之间的关联。方法对单中心系列 ARCI 遗传诊断患者的临床体征和症状以及疾病严重程度进行评分。结果连续有74名患者(平均年龄11.0岁,年龄范围0.1-48.8岁)患有板层状鱼鳞病(50/74,67.5%)、先天性鱼鳞状红皮病(18/74,24.3%)、鱼鳞病(2/74,2.7%)和其他轻微的ARCI亚型(4/74,5.4%)。突变基因有18/74(24.3%)例患者的 TGM1、18/74(24.3%)例患者的 ALOX12B、12/74(16.2%)例患者的 CYP4F22、9/74(12.2%)例患者的 ABCA12、7/74(9.5%)例患者的 ALOXE3、7/74(9.5%)例患者的 NIPAL4,以及 1/74(1.4%)例患者的 CERS3、PNPLA1 和 SDR9C7。在不同的ARCI致病基因中发现了25个以前未曾描述过的突变,以及TGM1中的两个微重复、CYP4F22和NIPAL4中的两个微缺失。TGM1和ABCA12基因突变患者的平均鱼鳞病严重程度评分明显高于所有其他基因突变患者,而CYP4F22基因突变患者的评分最低。脱发、外翻和clabium与TGM1和ABCA12基因突变明显相关,而大块、厚和褐色鳞屑与TGM1基因突变明显相关。在具体的表型特征中,NIPAL4 基因突变患者会出现牛皮癣样皮损、躯干网状鳞屑模式和条纹状角化病。56 例患者的超微结构数据显示,TGM1 突变病例的胆固醇裂隙特异性为 100%,SDR9C7 和 CERS3 患者的异常片状体也被发现。最后,我们强调了 NIPAL4-ARCI 患者中银屑病样皮损的存在,这是一种新的表型特征,具有诊断和可能的治疗意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cross-sectional study on autosomal recessive congenital ichthyoses: association of genotype with disease severity, phenotypic and ultrastructural features in 74 Italian patients.
BACKGROUND Autosomal recessive congenital ichthyoses (ARCI) are a clinically heterogeneous group of keratinization disorders characterized by generalized skin scaling due to mutations in at least 12 genes. The aim of our study was to assess disease severity, phenotypic and ultrastructural features and to evaluate their association with genetic findings in ARCI patients. METHODS Clinical signs and symptoms, and disease severity were scored in a single-center series of patients with a genetic diagnosis of ARCI. Skin ultrastructural findings were reviewed. RESULTS Seventy-four consecutive patients (mean age 11.0 years, range 0.1-48.8) affected with lamellar ichthyosis (50/74, 67.5%), congenital ichthyosiform erythroderma (18/74, 24.3%), harlequin ichthyosis (two/74, 2.7%), and other minor ARCI subtypes (four/74, 5.4%) were enrolled. Mutated genes were: TGM1 in 18/74 (24.3%) patients, ALOX12B in 18/74 (24.3%), CYP4F22 in 12/74 (16.2%), ABCA12 in nine/74 (12.2%), ALOXE3 in seven/74 (9.5%), NIPAL4 in seven/74 (9.5%), and CERS3, PNPLA1 and SDR9C7 in one patient each (1.4%). Twenty-five previously undescribed mutations in the different ARCI causative genes, as well as two microduplications in TGM1, and two microdeletions in CYP4F22 and NIPAL4 were identified. The mean ichthyosis severity score in TGM1 and ABCA12-mutated patients was significantly higher than in all other mutated genes, while the lowest score was observed in CYP4F22-mutated patients. Alopecia, ectropion, and eclabium were significantly associated with TGM1 and ABCA12 mutations, and large, thick and brownish scales with TGM1 mutations. Among specific phenotypic features, psoriasis-like lesions as well as a trunk reticulate scale pattern and striated keratoderma were present in NIPAL4-mutated patients. Ultrastructural data available for 56 patients showed a 100% specificity of cholesterol clefts for TGM1-mutated cases, and revealed abnormal lamellar bodies in SDR9C7 and CERS3 patients. CONCLUSION Our study expands the phenotypic and genetic characterization of ARCI by the description of statistically significant associations between disease severity, specific clinical signs, and different mutated genes. Finally, we highlighted the presence of psoriasis-like lesions in NIPAL4-ARCI patients as a novel phenotypic feature with diagnostic and possible therapeutic implications.
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
期刊介绍: ACS Applied Electronic Materials is an interdisciplinary journal publishing original research covering all aspects of electronic materials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials science, engineering, optics, physics, and chemistry into important applications of electronic materials. Sample research topics that span the journal's scope are inorganic, organic, ionic and polymeric materials with properties that include conducting, semiconducting, superconducting, insulating, dielectric, magnetic, optoelectronic, piezoelectric, ferroelectric and thermoelectric. Indexed/​Abstracted: Web of Science SCIE Scopus CAS INSPEC Portico
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