A case report of hereditary apolipoprotein A-I amyloidosis associated with a novel APOA1 mutation and variable phenotype

作者：Tougaard Birgitte G^*; Pedersen Katja Venborg; Krag Soren Rasmus; Gilbertson Janet A; Rowczenio Dorota; Gillmore Julian D; Birn Henrik

来源：European Journal of Medical Genetics, 2016, 59(9): 474-477.

DOI：10.1016/j.ejmg.2016.05.015

• Variable phenotype
• Hereditary
• Amyloidosis
• Apolipoprotein A-I encoding mutation
• APOA1

Apolipoprotein A-I (apo A-I) amyloidosis is a non-AL, non-AA, and non-transthyretin type of amyloidosis associated with mutations in the APOA1 gene inherited in an autosomal dominant fashion. It is a form of systemic amyloidosis, but at presentation, can also mimic localized amyloidosis. The renal presentation generally involves interstitial and medullary deposition of apo A- I amyloid protein. We describe the identification of apo A- I amyloidosis by mass spectrometry in a 52-year old male, with no family history of amyloidosis, presenting with nephrotic syndrome and associated with heterozygosity for a novel APOA1 mutation (c.220 T > A) which encodes the known amyloidogenic Trp50Arg variant. Renal amyloid deposits in this case were confined to the glomeruli alone, and the patient developed progressive renal impairment. One year after diagnosis, the patient had a successful kidney transplant from an unrelated donor. Pathogenic mutations in the APOA1 gene are generally associated with symptoms of amyloidosis. In this family however, genotyping of family members identified several unaffected carriers suggesting a variable disease penetrance, which has not been described before in this form of amyloidosis and has implications when counselling those with APOA1 mutations.

• 出版日期2016-9