Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?
Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?
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DOI：
10.1016/j.gene.2017.10.068
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发表时间：
2018-01-30
期刊：
影响因子：
3.5
通讯作者：
Cuppari, C.
中科院分区：
文献类型：
--
作者：
Procopio, V.;Manti, S.;Cuppari, C.
背景FMF病的发病机制、遗传模式以及基因型-表型相关性仍存在不确定性。目的：探讨遗传因素对FMF表型及疾病遗传模式的影响。方法：共纳入107例FMF患者。患者经临床诊断。所有患者均对16p13.3的FMF位点进行遗传分析。结果：检测到9个不同的突变。其中，85.98%的患者为杂合型。最常见的基因型是p.Met68011e/wt和p.Met694Val/wt。最常见的临床表现为发热、腹痛、关节痛、胸痛和丹毒样红斑。临床资料分析未发现杂合子、纯合子和复合纯合子受试者的临床表型有显著差异，进一步支持与隐性常染色体遗传相反，-杂合子患者符合临床FMF标准。此外，p.Met694Val/wt和p.Met680I1e/wt基因型的受试者报告了最严重的临床表型。p.A1a744Ser/wt、p.G1u148G1nMet68011e、p.Met680IIe/Met680Ile、p.Met680I1e/Met694Val、p.Pro369Ser/wt、p.Met694I1e/wt、p.G1u148GInGlu148G1n、p.Lys695Arg/wt致病性为100%。结论：不能排除FMF存在“非经典”常染色体隐性遗传和“非典型”显性常染色体遗传，其外显率不完全和表达性可变。
Background Uncertainty remains on the pathogenetic mechanisms, model of inheritance as well as genotype phenotype correlation of FMF disease.Objective: To investigate the impact of genetic factors on the FMF phenotype and the disease inheritance model.Methods: A total of 107 FMF patients were enrolled. Patients were diagnosed clinically. All patients underwent genetic analysis of the FMF locus on 16p13.3.Results: 9 distinct mutations were detected. Specifically, the 85.98% of patients showed a heterozygous genotype. The most common genotypes were p.Met68011e/wt and p.Met694Val/wt. The most frequent clinical findings were fever, abdominal pain, joint pain, thoracic pain, and erysipelas-like erythema. Analysis of clinical data did not detect any significant difference in clinical phenotype among heterozygous, homozygous as well as compound homozygous subjects, further supporting the evidence that, contrary to the recessive autosomal inheritance, -heterozygous patients fulfilled the criteria of clinical FMF. Moreover, subjects with p.Met694Val/wt and p.Met680I1e/wt genotype reported the most severe clinical phenotype. p.A1a744Ser/wt, p.G1u148G1nMet68011e, p.Met680IIe/Met680Ile, p.Met680I1e/Met694Val, p.Pro369Ser/wt, p.Met694I1e/wt, p.G1u148GInGlu148G1n, p.Lys695Arg/wt resulted in 100% pathogenicity.Conclusions: The existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance with incomplete penetrance and variable expressivity cannot be excluded in FMF.