ABSTRACT
BACKGROUND: Familial juvenile hyperuricemic nephropathy (FJHN) is a rare autosomal dominant disease caused by mutations in the uromodulin gene (UMOD) and leading to gout, tubulointerstitial nephropathy and end-stage renal disease. CASE REPORTS AND RESULTS: A Latvian family suffering from FJHN is described. The father of the family developed ESRD at age 36. His daughter was diagnosed with gout and chronic kidney disease at age 14 years. A renal biopsy revealed tubulointerstitial disease; 2 sons were diagnosed at age 9 and 4 with elevated uric acid levels and reduced fractional uric acid excretion. Urinary uromodulin was normal in the younger boy, but markedly decreased in the 2 other patients. Genetic analysis revealed a previously undescribed D196Y mutation in the UMOD gene. The female patient became pregnant at age 23. During pregnancy serum creatinine decreased from 2.0 to 1.5 mg/dl and blood pressure remained low. Analysis of the baby's umbilical cord blood and a mouth swab showed the presence of the D196Y mutation. Its urinary uromodulin excretion was in the low normal range. CONCLUSION: The uromodulin excretion pattern observed in the investigated family suggests that urinary uromodulin decreases in FJHN from low normal values at childhood to extremely low levels in early adulthood. In addition, this first report on pregnancy in a patient with FJHN shows normal adaptation despite markedly reduced renal function.
Subject(s)
Hyperuricemia/genetics , Kidney Diseases/genetics , Mucoproteins/genetics , Mutation/genetics , Pregnancy Complications/genetics , Adolescent , Age Factors , Child, Preschool , Female , Humans , Hyperuricemia/metabolism , Hyperuricemia/therapy , Infant, Newborn , Kidney Diseases/metabolism , Kidney Diseases/therapy , Male , Mucoproteins/metabolism , Pedigree , Pregnancy , Pregnancy Complications/metabolism , Pregnancy Complications/therapy , Pregnancy Outcome , Uromodulin , Young AdultABSTRACT
The crucifer oilseed plant false flax (Camelina sativa subsp. sativa) possesses numerous valuable agronomic attributes that make it attractive as an alternative spring-sown crop for tight crop rotations. The oil of false flax is particularly rich in polyunsaturated C18-fatty acids, making it a valuable renewable feedstock for the oleochemical industry. Because of the minimal interest in the crop throughout the 20th century, breeding efforts have been limited. In this study, a genetic map for C. sativa was constructed, using amplified fragment length polymorphism (AFLP) markers, in a population of recombinant inbred lines that were developed, through single-seed descent, from a cross between 'Lindo' and 'Licalla', 2 phenotypically distinct parental varieties. Three Brassica simple sequence repeat (SSR) markers were also integrated into the map, and 1 of these shows linkage to oil-content loci in both C. sativa and Brassica napus. Fifty-five other SSR primer combinations showed monomorphic amplification products, indicating partial genome homoeology with the Brassica species. Using data from field trials with different fertilization treatments (0 and 80 kg N/ha) at multiple locations over 3 years, the map was used to localize quantitative trait loci (QTLs) for seed yield, oil content, 1000-seed mass, and plant height. Some yield QTLs were found only with the N0 treatment, and might represent loci contributing to the competitiveness of false flax in low-nutrient soils. The results represent a starting point for future marker-assisted breeding.