title: Variable renal phenotype in a family with an INF2 mutation.
abstract: Recent advances in the genetics of glomerular diseases have identified several causative genes of nephrotic syndrome and/or glomerular proteinuria. In 2010, the INF2 gene, which encodes a member of the formin family of actin-regulating proteins, was identified as a novel causative gene of the autosomal dominant form of focal segmental glomerulosclerosis (FSGS). Here, we describe an additional familial case of FSGS associated with INF2 mutations. In the family, two siblings and their father had a heterozygous p.E220K mutation on INF2. This mutation manifested in these three individuals as incidentally detected proteinuria without overt nephrotic syndrome, but at different ages of 7, 9, and 30 years, respectively. Two siblings had nephrotic range proteinuria, and one developed end-stage renal disease 5 years later. Conversely, their father had a modest degree of proteinuria, and maintained normal renal function until age 47. A renal biopsy of one of the siblings revealed FSGS with irregular podocyte foot process morphology and focal glomerular basement membrane changes. This is the second paper describing a familial case of FSGS associated with INF2 mutations as well as intrafamilial phenotype variability.
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, 101 Daehang-no, Jongno-Gu, Seoul, 110-744, Korea.
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Kyoung Hee
authors.initials: KH
authors.lastname: Han
authors.forename: Yun Hye
authors.initials: YH
authors.lastname: Jung
authors.forename: Hee Gyung
authors.initials: HG
authors.lastname: Kang
authors.forename: Kyung Chul
authors.initials: KC
authors.lastname: Moon
authors.forename: Il Soo
authors.initials: IS
authors.lastname: Ha
authors.forename: Yong
authors.initials: Y
authors.lastname: Choi
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Cheong
mesh_terms: D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D000080865:Formins; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D050199:Podocytes / Q000473:pathology; D011507:Proteinuria / Q000235:genetics*
chemical_list: D000080865:Formins; C546959:INF2 protein, human; D008840:Microfilament Proteins
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