Renal Dysplasia in a Family With Multiple Hereditary Abnormalities Including Iliac Horns

Hawkins, C F; Smith, Olivia Eilers

doi:10.1016/s0140-6736(50)90636-2

Cited by 106 publications

(28 citation statements)

References 11 publications

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“…9 -12 Nephropathy and glaucoma are the most relevant clinical manifestations in human NPS. 13,14 NPS nephropathy is a disease of both the podocytes and the GBM, with irregular thickening and electron lucent areas as consistent ultrastructural hallmarks of the GBM. 7,15,16 Interestingly, abnormal collagen expression has been observed in human NPS renal biopsy specimens 15 and in Lmx1b À/À murine kidneys 5 and corneal stroma.…”

Section: Introductionmentioning

confidence: 99%

Genotype–phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy

et al. 2005

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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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Section: Introductionmentioning

confidence: 99%

Genotype–phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy

et al. 2005

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“…More than 60 years later, Lichter et al [15] described cosegregation of primary open-angle glaucoma (POAG) and NPS in 50% of NPS patients (12/24) from two families, and suggested this ocular anomaly to be a variable feature of NPS. Since 1950, the involvement of renal pathology in NPS has been recognized [14,16,17] and confirmed by the identification of typical changes of the GBM at the ultrastructural level [18,19,20]. Depression and anxiety symptoms, epilepsy, peripheral neurological symptoms, and gastrointestinal complaints, including irritable bowel syndrome and constipation, have recently been suggested to be associated with NPS [21,22,23].…”

Section: Introductionmentioning

confidence: 99%

Nail-patella syndrome. Overview on clinical and molecular findings

Bongers

Gubler

Knoers

2002

Pediatric Nephrology

159

133

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Nail-patella syndrome (NPS) is a rare autosomal dominant pleiotropic disorder characterized by dysplasia of the nails, patellar aplasia or hypoplasia, iliac horns, dysplasia of the elbows, and frequently glaucoma and progressive nephropathy. The recent identification of the causative gene for this syndrome has initiated further studies of the phenotype and molecular pathogenesis of kidney disease in NPS. The gene underlying NPS, LMX1B, is a LIM-homeodomain transcription factor involved in normal patterning of the dorsoventral axis of the limb during development and early morphogenesis of the glomerular basement membrane. Molecular studies of Lmx1b, combined with genetic and immunohistochemical investigation of different alpha chains of type IV collagen in the Lmx1b null mice kidney, a mouse model for NPS, have provided evidence that Lmx1b is involved in the pathogenesis of NPS glomerulopathy. At present evidence for a correlation between the presence and severity of the renal and extrarenal anomalies and LMX1B genotype is lacking. This review focuses on the recent advances in clinical and molecular genetic studies of NPS.

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“…In further publications the phenotype was expanded and the dominant inheritance of the disorder was clarified. [4][5][6][7][8][9] Linkage of NPS to the ABO blood group locus and the adenylate kinase 1 (AK1) gene on chromosome 9 were among the first autosomal linkages for a genetic disorder to be established in humans. 10 Linkage of NPS to loci on 9q has been confirmed in all informative families that have been studied.…”

Section: Introductionmentioning

confidence: 99%

Nail patella syndrome in a cytogenetically balanced t(9;17)(q34.1;q25) carrier

et al. 1998

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Nail patella syndrome (NPS) is an autosomal dominant disorder characterized by dysplasia of the nails and patella, decreased mobility of the elbow, iliac horns and in some cases nephropathy. Linkage studies have localized the NPS locus to chromosome 9q34 within a 1-2 cM interval between D9S60 and the adenylate kinase gene (AK1), but the gene has remained elusive. We have identified a balanced t(9;17)(q34.1;q25) associated with NPS. By using FISH with probes from 9q the breakpoint region was narrowed to a 17.0 cM interval between D9S262 and ABL, which includes the NPS critical region. The patient showed the typical clinical features of NPS such as hypoplastic, deep-set nails, a dislocated elbow, iliac horns, and a polygonal patella. This suggests that the translocation has resulted from a break within or near the NPS gene, causing defective expression. The translocation in our patient may aid in the identification of the NPS gene.

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Renal Dysplasia in a Family With Multiple Hereditary Abnormalities Including Iliac Horns

Cited by 106 publications

References 11 publications

Genotype–phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy

Genotype–phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy

Nail-patella syndrome. Overview on clinical and molecular findings

Nail patella syndrome in a cytogenetically balanced t(9;17)(q34.1;q25) carrier

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