All the mutations affect the homeodomain of the LMX1B protein and could cause the Nail-Patella syndrome through a loss of function as well as a dominant negative effect.
Variants in the LMX1B gene cause nail-patella syndrome, a rare autosomal dominant disorder characterized by dysplasia of nails, patella and elbow abnormalities, iliac "horns," and glaucoma.
Nail-patella syndrome (NPS) is rare genetic disorder with autosomal mode of inheritance resulting from mutations in the LMX1B gene mapped on the long arm of chromosome 9 (9q34), encoding transcription factor, also named LMX1B.
In the present study, we analyzed the LMX1B gene in three Japanese patients with NPS and identified two novel mutations, 6 nucleotide deletion (Delta246N 247Q) and V242L.
This is the first report that a mutation in the LMX1B gene causes NPS in a Chinese population, which will expand the spectrum of mutations in the LMX1B gene and provide insight into the underlining pathology of NPS.
Here, we present exome sequencing and analysis of four generations of a family with a dominantly inherited Nail-Patella-like disorder (nail dysplasia with some features of Nail-Patella syndrome) who tested negative forLMX1B mutation.
The identification of entire LMX1B deletions strongly confirms that haploinsufficiency is the principal pathogenetic mechanism of NPS and suggests a difference in dosage sensitivity for this gene between mice and man.
This suggests that the locus 9q33-9q34 can be excluded for GPS and that the presented case is unique in its combination of GPS and NPS features caused by a microdeletion associated with loss of function of LMX1B and NR5A1.
NPS is inherited as an autosomal dominant trait and caused by heterozygous loss of function mutations in LMX1B, a member of the LIM homeodomain protein family.
Previous studies have identified mutations in the RSPO4 and LMX1B components of the Wnt pathway in patients with the hypoplastic nail disorders anonychia and nail-patella syndrome, respectively.
Co-occurrence of familial Mediterranean fever (FMF) heterozygote mutation and nail-patella syndrome (NPS) in 3 members of a family with LMX1B mutation analysis.
This is the first report of familial nail-patella syndrome associated with an LMX1B in Korea mutation, However, we can not completely rule out the possibility that the G-to-C change may be a single nucleotide polymorphism as this genetic mutation cause no alteration in amino acid sequence of LMX1B.
NPS is inherited as an autosomal dominant trait and caused by heterozygous loss of function mutations in LMX1B, a member of the LIM homeodomain protein family.
Sequencing of the CLIM2 coding region in seven NPS cases in which no LMX1B mutation had been found, did not detect any molecular variant in these patients.
The underlying molecular etiology in NPS is the mutation of <i>LMX1B</i> homeobox gene which results in loss of function of its protein also called LMX1B, a DNA-binding protein belonging to the larger LIM-homeodomain transcription factor family.
Nail-patella syndrome (NPS) or hereditary onycho-osteodyaplasia is a rare genetic condition involving a mutation in the LMX1B gene affecting nails, elbows, knees, and pelvis.