LMX1B Mutations Cause Hereditary FSGS without Extrarenal Involvement

作者：Boyer Olivia; Woerner Stephanie; Yang Fan; Oakeley Edward J; Linghu Bolan; Gribouval Olivier; Tete Marie Josephe; Duca Jose S; Klickstein Lloyd; Damask Amy J; Szustakowski Joseph D; Heibel Francoise; Matignon Marie; Baudouin Veronique; Chantrel Francois; Champigneulle Jacqueline; Martin Laurent; Nitschke Patrick; Gubler Marie Claire; Johnson Keith J; Chibout Salah Dine; Antignac Corinne^*

来源：Journal of the American Society of Nephrology, 2013, 24(8): 1216-1222.

DOI：10.1681/ASN.2013020171

LMX1B encodes a homeodomain-containing transcription factor that is essential during development. Mutations in LMX1B cause nail-patella syndrome, characterized by dysplasia of the patellae, nails, and elbows and FSGS with specific ultrastructural lesions of the glomerular basement membrane (GBM). By linkage analysis and exome sequencing, we unexpectedly identified an LMX1B mutation segregating with disease in a pedigree of five patients with autosomal dominant FSGS but without either extrarenal features or ultrastructural abnormalities of the GBM suggestive of nail-patella-like renal disease. Subsequently, we screened 73 additional unrelated families with FSGS and found mutations involving the same amino acid (R246) in 2 families. An LMX1B in silico homology model suggested that the mutated residue plays an important role in strengthening the interaction between the LMX1B homeodomain and DNA; both identified mutations would be expected to diminish such interactions. In summary, these results suggest that isolated FSGS could result from mutations in genes that are also involved in syndromic forms of FSGS. This highlights the need to include these genes in all diagnostic approaches to FSGS that involve next-generation sequencing.

• 出版日期2013-7-31