A novel mutation, outside of the candidate region for diagnosis, in the inverted formin 2 gene can cause focal segmental glomerulosclerosis.
A novel mutation, outside of the candidate region for diagnosis, in the inverted formin 2 gene can cause focal segmental glomerulosclerosis.
复制标题
倒置福明 2 基因中在候选诊断区域之外的新突变可导致局灶节段性肾小球硬化。
作者：
María Sánchez;Marina Garcia;Espinosa;Pardo Julio;Vazquez;X. Lens;M. García
局灶性节段性肾小球硬化症 (FSGS) 是一种组织学模式，有多种病因，包括遗传学。常染色体显性遗传形式的 FSGS 是一种异基因性疾病，由三个已知基因突变引起：α-辅肌动蛋白 4 (ACTN4)、经典瞬时受体电位 6 (TRPC6) 和反向福尔敏 2 (INF2) 基因。最近，INF2 突变也被归因于与 FSGS 相关的腓骨肌神经病。在这里，我们对一组常染色体显性 FSGS 家族进行了直接测序、组织学表征和功能研究。我们在用于快速诊断常染色体显性 FSGS 的外显子 2-4 候选区域之外的 INF2 基因的外显子 6 中检测到了一个新的突变。预计这种新突变会改变蛋白质透明抑制结构域第 17 个 α 螺旋内高度保守的氨基酸残基。对这个家庭的长期随访表明，所有患者都是在成年期而不是儿童早期被诊断出来的，并且进展为终末期肾病的时间不同，没有神经病变的临床或电诊断证据。因此，INF2 中与非综合征 FSGS 相关的新突变表明，如果在当前的基因快速筛选区域中没有发现突变，则需要进行完整的基因测序。
Focal and segmental glomerulosclerosis (FSGS) is a histological pattern that has several etiologies, including genetics. The autosomal dominant form of FSGS is a heterogenic disease caused by mutations within three known genes: α-actinin 4 (ACTN4), canonical transient receptor potential 6 (TRPC6), and the inverted formin 2 (INF2) gene. More recently, INF2 mutations have also been attributed to Charcot-Marie-Tooth neuropathy associated with FSGS. Here we performed direct sequencing, histological characterization, and functional studies in a cohort of families with autosomal dominant FSGS. We detected a novel mutation in exon 6 of the INF2 gene outside of the exon 2-4 candidate region used for rapid diagnosis of autosomal dominant FSGS. This new mutation is predicted to alter a highly conserved amino-acid residue within the 17th α-helix of the diaphanous inhibitory domain of the protein. A long-term follow-up of this family indicated that all patients were diagnosed in adulthood, as opposed to early childhood, and progression to end-stage renal disease was at different times without clinical or electrodiagnostic evidence of neuropathy. Thus, this novel mutation in INF2 linked to nonsyndromic FSGS indicates the necessity for full gene sequencing if no mutation is found in the current rapid-screen region of the gene.
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影响因子：
3.5
作者：
Garcia-Gonzalez, Miguel A.;Menezes, Luis F.;Germino, Gregory G.
通讯作者：
Germino, Gregory G.
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通讯作者：
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