Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present here the first described case of Nail-patella syndrome (NPS) and pregnancy. Complications occurred during the pregnancy with the onset of preeclampsia at 22 weeks, leading to intrauterine fetal death at 24 weeks. The nephropathy of the NPS began clinically during the course of gestation. Postpartum, it persisted as isolated proteinuria, which became a nephrotic syndrome 18 months later.
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PMID:Nail-patella syndrome and pre-eclampsia. 816 40

Nail-patella syndrome (NPS) is a rare, autosomal-dominant hereditary disorder characterized by nail dysplasia and multiple osseous abnormalities. Some patients may develop renal function impairment and even end-stage renal disease. We treated a 42-year-old female patient with proteinuria who presented with a web-like structure over the antecubital fossa and hypoplastic patellae. In addition, she had other characteristic findings, including bilateral iliac horn, triangular nail lunulae and hypoplastic radial head. She had impaired renal function, and renal biopsy showed mesangial proliferative glomerulonephritis. Additional cases were found in her family. Her mother had most of the signs of NPS as well as advanced renal failure. Her elder sister had knee abnormalities without the web-like elbow condition. Both daughters also had the characteristic features of NPS. During follow-up 30 months after the initial examination, the patient had stable renal function and mild proteinuria.
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PMID:Nail-patella syndrome with renal involvement and antecubital pterygia. 1264 95

Nail-patella syndrome (NPS) is characterized by developmental defects of dorsal limb structures, nephropathy, and glaucoma and is caused by heterozygous mutations in the LIM homeodomain transcription factor LMX1B. In order to identify possible genotype-phenotype correlations, we performed LMX1B mutation analysis and comprehensive investigations of limb, renal, ocular, and audiological characteristics in 106 subjects from 32 NPS families. Remarkable phenotypic variability at the individual, intrafamilial, and interfamilial level was observed for different NPS manifestations. Quantitative urinanalysis revealed proteinuria in 21.3% of individuals. Microalbuminuria was detected in 21.7% of subjects without overt proteinuria. Interestingly, nephropathy appeared significantly more frequent in females. A significant association was established between the presence of clinically relevant renal involvement in an NPS patient and a positive family history of nephropathy. We identified normal-tension glaucoma (NTG) and sensorineural hearing impairment as new symptoms associated with NPS. Sequencing of LMX1B revealed 18 different mutations, including six novel variants, in 28 families. Individuals with an LMX1B mutation located in the homeodomain showed significantly more frequent and higher values of proteinuria compared to subjects carrying mutations in the LIM domains. No clear genotype-phenotype association was apparent for extrarenal manifestations. This is the first study indicating that family history of nephropathy and mutation location might be important in precipitating individual risks for developing NPS renal disease. We suggest that the NPS phenotype is broader than previously described and that NTG and hearing impairment are part of NPS. Further studies on modifier factors are needed to understand the mechanisms underlying phenotypic heterogeneity.
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PMID:Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy. 1592 87

Nail-patella syndrome (NPS) is a pleiotropic autosomal-dominant disorder due to mutations in the gene LMX1B. It has traditionally been characterized by a tetrad of dermatologic and musculoskeletal abnormalities. However, one of the most serious manifestations of NPS is kidney disease, which may be present in up to 40% of affected individuals. Although LMX1B is a developmental LIM-homeodomain transcription factor, it is expressed in post-natal life in the glomerular podocyte, suggesting a regulatory role in that cell. Kidney disease in NPS seems to occur more often in some families with NPS, but it does not segregate with any particular mutation type or location. Two patterns of NPS nephropathy may be distinguished. Most affected individuals manifest only an accelerated age-related loss of filtration function in comparison with unaffected individuals. Development of symptomatic kidney failure is rare in this group, and proteinuria (present in approximately one-third) does not appear to be progressive. A small minority (5-10%) of individuals with NPS develop nephrotic-range proteinuria as early as childhood or young adulthood and progress to end-stage kidney failure over variable periods of time. It is proposed that this latter group reflects the effects of more global podocyte dysfunction, possibly due to the combination of a mutation in LMX1B along with an otherwise innocuous polymorphism or mutation involving any of several genes expressed in podocytes (e.g. NPHS2, CD2AP), the transription of which is regulated by LMX1B.
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PMID:Kidney disease in nail-patella syndrome. 1853 45

Nail-patella syndrome (NPS) is a rare, autosomal dominant disorder reported in approximatively 1/50,000 individuals. It is characterized by hypoplastic or absent patellae, dystrophic nails, dysplasia of the elbows and iliac horns. Less frequently renal and ocular damages occur. The abnormal gene in NPS is located at the distal end of the long arm of Chromosome 9. Mutations in the human LMX1B gene have been demonstrated to be responsible for NPS. It encodes a LIM-homeodomain transcription factor which plays an important role in limb development in vertebrates. Extensive mutation analysis of different NPS families by different groups failed to demonstrate any genotype-phenotype correlation. Renal involvement occurs in 30-60% of patients and presents with proteinuria and/or microscopic hematuria, edema, hypertension. Progression to nephrotic syndrome occurs in less than 20% of patients, and renal failure in about 10% of NPS patients requiring dialysis and/or transplantation. We report three cases of NPS with different degrees of renal involvement and present a review of the literature on this rare hereditary condition.
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PMID:Nail-patella syndrome and renal involvement. Description of three cases and literature review. 1853 2

We describe a 6-year-old girl presenting with nail dysplasia affecting all nails and hands for 2 years. Changes were seen on the ulnar side of the nails. She was assessed for limitation of elbow movements at 3 weeks of age and underwent physiotherapy for thickened biceps tendon. She subsequently developed laxity of knees and ankles, and x-ray revealed absent patellae at 32 weeks. She had behavioral abnormalities and sleep disturbances. X-ray of the pelvis revealed iliac horns, and urinalysis showed 3+ proteinuria. She had mixed hyperlipidemia. Her chromosomal analysis was normal but showed a mutation in the LMX1B gene. She was diagnosed to have Nail-patella syndrome or Hereditary osteo-onychodysplasia (HOOD Syndrome). Her renal imaging was normal, as were her ocular pressures. She is under regular surveillance by a multi-disciplinary team of genetic counselors, orthopedists, rheumatologists and ophthalmologists. She is currently prescribed enalapril, melatonin and simvastatin.
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PMID:Nail-patella syndrome with an emphasis on the risk of renal and ocular findings. 2019 24

End-stage renal disease (ESRD) presenting in a familial autosomal dominant pattern points to an underlying monogenic cause. Nail-patella syndrome (NPS) is an autosomal dominant disorder that may lead to ESRD caused by mutations in the transcription factor LMX1B. Renal-limited forms of this disease, termed nail-patella-like renal disease (NPLRD), and LMX1B nephropathy have recently been described. We report a large family, from the North East of England, with seven affected members with varying phenotypes of renal disease, ranging from ESRD at 28 years of age to microscopic haematuria and proteinuria and relatively preserved renal function. In this family, there were no extra-renal manifestations to suggest NPS. Genome-wide linkage studies and inheritance by descent (IBD) suggested disease loci on Chromosome 1 and 9. Whole exome sequencing (WES) analysis identified a novel sequence variant (p.R249Q) in the LMX1B gene in each of the three samples submitted, which was confirmed using Sanger sequencing. The variant segregated with the disease in all affected individuals. In silico modelling revealed that R249 is putatively located in close proximity to the DNA phosphoskeleton, supporting a role for this residue in the interaction between the LMX1B homeodomain and its target DNA. WES and analysis of potential target genes, including CD2AP, NPHS2, COL4A3, COL4A4 and COL4A5, did not reveal any co-inherited pathogenic variants. In conclusion, we confirm a novel LMX1B mutation in a large family with an autosomal dominant pattern of nephropathy. This report confirms that LMX1B mutations may cause a glomerulopathy without extra-renal manifestations. A molecular genetic diagnosis of LMX1B nephropathy thus provides a definitive diagnosis, prevents the need for renal biopsies and allows at risk family members to be screened.
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PMID:A novel LMX1B mutation in a family with end-stage renal disease of 'unknown cause'. 2571 21

Nail-patella syndrome (NPS) is an autosomal-dominant disease caused by LMX1B mutations and is characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. Renal involvement is the major determinant of the prognosis for NPS. Patients often present with varying degrees of proteinuria or hematuria, and can occasionally progress to chronic renal failure. Recent genetic analysis has found that some mutations in the homeodomain of LMX1B cause isolated nephropathy without nail, patellar or skeletal abnormality (LMX1B-associated nephropathy). The classic term "nail-patella syndrome" would not represent disease conditions in these cases. This review provides an overview of NPS, and highlights the molecular genetics of NPS nephropathy and LMX1B-associated nephropathy. Our current understanding of LMX1B function in the pathogenesis of NPS and LMX1B-associated nephropathy is also presented, and its downstream regulatory networks discussed. This recent progress provides insights that help to define potential targeted therapeutic strategies for LMX1B-associated diseases.
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PMID:Spectrum of LMX1B mutations: from nail-patella syndrome to isolated nephropathy. 2745 Mar 97

Nail-patella syndrome (NPS) is a multi-system disorder characterized by hypoplastic nails, hypoplastic patella, skeletal deformities, and iliac horns, which is caused by heterozygous variants of LMX1B. Nephropathy ranging from mild urinary abnormality to end-stage renal disease occurs in some individuals with NPS. Because of the low prevalence of NPS and the lack of longitudinal studies of its kidney involvement, the clinical, pathological, and genetic features characterizing severe nephropathy remain unclear. We conducted a Japanese survey of NPS with nephropathy, and analyzed their clinical course, pathological features, and factors associated with severe renal phenotype. LMX1B gene analysis and luciferase reporter assay were also performed. Among 13 NPS nephropathy cases with genetic validation, 5 patients who had moderate-to-massive proteinuria progressed to advanced chronic kidney disease or end-stage renal disease. Pathological findings in the early phase did not necessarily correlate with renal prognosis. Variants associated with deteriorated renal function including a novel variants were confined to the N-terminal region of the LIM domain and a short sequence in the LMX1B homeodomain, which were distinct from reported variants found in isolated nephropathy without extrarenal manifestation (LMX1B-associated nephropathy). Luciferase reporter analysis demonstrated that variants in patients with severe renal phenotype caused haploinsufficiency, but no dominant-negative effects on promoter activation. A distinct proportion of NPS nephropathy patients progressed to end-stage renal disease in adolescence or young adulthood. Patients with moderate or severe proteinuria, especially those with variants in specific regions of LMX1B, should be monitored for potential deterioration of renal function.
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PMID:Clinical and genetic characterization of nephropathy in patients with nail-patella syndrome. 3245 16