Novel INF2 mutations in an Italian cohort of patients with focal segmental glomerulosclerosis, renal failure and Charcot-Marie-Tooth neuropathy
Novel INF2 mutations in an Italian cohort of patients with focal segmental glomerulosclerosis, renal failure and Charcot-Marie-Tooth neuropathy
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DOI：
10.1093/ndt/gfu071
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发表时间：
2014-09-01
影响因子：
6.1
通讯作者：
Ghiggeri, Gian Marco
中科院分区：
文献类型：
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作者：
Caridi, Gianluca;Lugani, Francesca;Ghiggeri, Gian Marco
背景INF 2突变代表家族性常染色体显性（AD）局灶节段性肾小球硬化（FSGS）的主要原因。少数患者出现腓骨肌萎缩症（CMT）的神经系统症状，但其患病率尚未评估。我们筛查了28个患有AD FSGS的家庭，并在9个家庭（总共32名患者）中发现了8个INF 2突变，其中3个是新的。所有突变均位于蛋白质的透明抑制结构域（DID）。在我们的患者队列中，与INF 2突变相关的临床特征包括轻度蛋白尿（1.55 g/L;范围1-2.5）和血尿，血尿是一种独特的症状，在中位年龄21.75岁（范围8-30）时被发现。18例患者在生命的第三个十年期间发生终末期肾病; 12例患者的肌酐范围为1.2 - 1.5 mg/dL，2例患者在45岁和54岁时健康。CMT被诊断为4例（12.5%），其中1例患者在INF 2外显子2上出现已知突变，而其他患者在外显子4上出现相同突变，该区域以前与CMT无关。我们证实了AD FSGS家族中INF 2突变的高发病率。在疾病开始时临床表型是轻度的，但演变为终末期肾病是频繁的。CMT的发病率首次计算为突变携带者的12.5%。我们的研究结果支持INF 2基因分析的家庭中，肾功能衰竭和/或神经感觉缺陷的遗传后，AD模型。
Background. Mutations of INF2 represent the major cause of familial autosomal dominant (AD) focal segmental glomerulosclerosis (FSGS). A few patients present neurological symptoms of Charcot-Marie-Tooth (CMT) disease but the prevalence of the association has not been assessed yet.Methods. We screened 28 families with AD FSGS and identified 8 INF2 mutations in 9 families (32 patients overall), 3 of which were new. Mutations were in all cases localized in the diaphanous-inhibitory domain (DID) of the protein.Results. Clinical features associated with INF2 mutations in our patient cohort included mild proteinuria (1.55 g/L; range 1-2.5) and haematuria as a unique symptom that was recognized at a median age of 21.75 years (range 8-30). Eighteen patients developed end-stage renal disease during their third decade of life; 12 patients presented a creatinine range between 1.2 and 1.5 mg/dL and 2 were healthy at 45 and 54 years of age. CMT was diagnosed in four cases (12.5%); one of these patients presented an already known mutation on exon 2 of INF2, whereas the other patients presented the same mutation on exon 4, a region that was not previously associated with CMT.Conclusions. We confirmed the high incidence of INF2 mutations in families with AD FSGS. The clinical phenotype was mild at the onset of the disease, but evolution to ESRD was frequent. The incidence of CMT has, for the first time, been calculated here to be 12.5% of mutation carriers. Our findings support INF2 gene analysis in families in which renal failure and/or neuro-sensorial defects are inherited following an AD model.