Novel gelsolin variant as the cause of nephrotic syndrome and renal amyloidosis in a large kindred.

Efebera YA, Sturm A, Baack EC, Hofmeister CC, Satoskar A, Nadasdy T, Nadasdy G, Benson DM, Gillmore JD, Hawkins PN, Rowczenio D
Amyloid 21 110-2 06/01/2014


Familial Amyloidosis of Finnish type (FAF) is a rare type of autosomal dominant hereditary amyloidosis associated with genetic variants of gelsolin. Three amyloidogenic mutations have previously been reported characteristically presenting with ophthalmologic abnormalities, progressive cranial neuropathy and cutis laxa. We report a novel gelsolin variant in a 62-year-old man with nephrotic range proteinuria of 13.2 grams/day as the only presenting symptom. Renal biopsy followed by laser micro-dissection and mass spectrometry showed amyloidosis derived from gelsolin. DNA sequencing revealed the novel gelsolin mutation (c.633C > A) encoding p.N211K protein variant. Four of 13 asymptomatic family members were found to be heterozygous for the p.N211K mutation, three of whom had proteinuria of varying degree including one who proceeded to renal biopsy and was confirmed to have renal amyloidosis. Follow-up of these cases might give us more insight into pathogenicity and potential treatment strategy of this atypical presentation of gelsolin amyloidosis.

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