A novel mutation, outside of the candidate region for diagnosis, in the inverted formin 2 gene can cause focal segmental glomerulosclerosis

作者：Sanchez Ares Maria^*; Garcia Vidal Marina; Antucho Espinosa Estevez; Julio Pardo; Eduardo Vazquez Martul; Lens Xose M; Garcia Gonzalez Miguel A

来源：Kidney International, 2013, 83(1): 153-159.

DOI：10.1038/ki.2012.325

• diagnosis
• focal segmental glomerulosclerosis
• INFZ
• mutation

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: alpha-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 alpha-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. Kidney International (2012) 83, 153-159; doi:10.1038/ki.2012.325; published online 12 September 2012

• 出版日期2013-1