Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2004
Functional consequences of a novel uromodulin mutation in a family with familial juvenile hyperuricaemic nephropathy.
Клинический случайСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Tinschert Sigrid, Ruf Nico, Bernascone Ilenia, Sacherer Kai, Lamorte Giuseppe, Neumayer Hans-Hellmut, Nürnberg Peter, Luft Friedrich C, Rampoldi Luca
Аннотация
BACKGROUND: Familial juvenile hyperuricaemic nephropathy (FJHN) is an autosomal-dominant disorder featuring hyperuricaemia, low fractional urate excretion, interstitial nephritis and chronic renal failure. The responsible gene UMOD was recently identified. UMOD encodes for uromodulin or Tamm-Horsfall glycoprotein, the most abundant protein in normal urine. We encountered a family with FJHN and identified a novel UMOD mutation in exon 6.
METHODS: We sequenced the gene in all family members, identified the mutation, and verified its presence in the affected members. We next performed functional studies of the mutant protein by immunofluorescence and FACS analysis on transfected cells.
RESULTS: The mutation p.C347G (c.1039T > G) results in a conserved cysteine to glycine amino acid substitution in the uromodulin zona pellucida (ZP) domain. The cell studies showed that the novel uromodulin mutation causes a delay in protein export to the plasma membrane due to its retention in the endoplasmic reticulum.
CONCLUSIONS: We describe the first reported mutation mapping in the ZP uromodulin domain. Our data provide further evidence showing why the excretion of uromodulin is reduced in this syndrome.
METHODS: We sequenced the gene in all family members, identified the mutation, and verified its presence in the affected members. We next performed functional studies of the mutant protein by immunofluorescence and FACS analysis on transfected cells.
RESULTS: The mutation p.C347G (c.1039T > G) results in a conserved cysteine to glycine amino acid substitution in the uromodulin zona pellucida (ZP) domain. The cell studies showed that the novel uromodulin mutation causes a delay in protein export to the plasma membrane due to its retention in the endoplasmic reticulum.
CONCLUSIONS: We describe the first reported mutation mapping in the ZP uromodulin domain. Our data provide further evidence showing why the excretion of uromodulin is reduced in this syndrome.