Nail-patella syndrome. Overview on clinical and molecular findings

Abstract

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.

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

“…Previous ultrastructural studies of renal biopsy specimens of the latter patient demonstrated typical GBM anomalies characteristic for NPS. 33 None of the unaffected relatives of NPS family 26 were reported to have nephropathy.…”

Congenital patellofemoral joint problems

“…Hastalık, tırnaklarda bozukluklar, radius başı hipoplazisi, posteriyor iliyak çıkıntılar üstünde veya kenarında 'iliyak boynuz''ların gelişmesi, patellanın hipoplazisi veya tamamen yokluğu ile karakterizedir. [17] Patellanın radyografik olarak tespit edilebilen bozuklukları, oval veya üçgen şekilli patella veya patella baja'dır. Bu tarz patellar bozukluklar sık görülmesine rağmen, tırnak-patella sendromunda belirgin fonksiyonel yetmezlik nadiren tespit edilir.…”

“…[18,19] Ek olarak, lateral femoral kondil hipoplazisi, interkondiler çentikte genişleme, lateral femoral kondilde osteokondral defekt, tibial tüberkülde belirginleşme, fibula başı hipoplazisi, genu valgum veya varum, pes ekinovarus, kalça displazisi ve büyük eklem kontraktürleri görülebilir. [17,20] Nadiren, aşırı genu valgum gelişen olgularda, düzeltici tibial osteotomilere gereksinim duyulabilir.…”

Interaction of the LMX1B and PAX2 gene products suggests possible molecular basis of differential phenotypes in Nail–Patella syndrome

“…1,2 The LMX1B gene is responsible for the NPS and for NPS associated with OAG, and it encodes a LIM-homeodomain protein. 1 A wide inter-and intrafamilial variability has been described for skeletal abnormalities, presence and severity of nephropathy and ocular anomalies. No significant genotype -phenotype correlation has been reported.…”

“…No significant genotype -phenotype correlation has been reported. 1 The LMX1B gene plays a pivotal role in embryo development in particular for limb development, kidney morphogenesis and development of the anterior segment of the eye. 3 -5 Phenotype variability might well be ascribed to interactions with other developmental genes, especially considering the properties of the LMX1B gene, whose LIM domain favors protein -protein interaction.…”