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

作者：Efebera Yvonne A^*; Sturm Amy; Baack Elizabeth C; Hofmeister Craig C; Satoskar Anjali; Nadasdy Tibor; Nadasdy Gyongyi; Benson Don M; Gillmore Julian D; Hawkins Philip N; Rowczenio Dorota

来源：Amyloid-Journal of Protein Folding Disorders, 2014, 21(2): 110-112.

DOI：10.3109/13506129.2014.891502

• Amyloidosis
• gelsolin
• proteinuria

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.

• 出版日期2014-6