Connexion

GENATLAS PHENOTYPE

last update : 05-12-2008

Symbol	NPS1
Location	9q34.1
Name	nail patella syndrome
Other name(s)	Turner-Kieser syndrome onychoosteodysplasia Fong disease
Corresponding gene	LMX1B
Main clinical features	nail dysplasia, joint stiffness, patella aplasia or hypoplasia, elbow dysplasia, and iliac horns kidney disease, hearing loss and normal tension glaucoma in some cases clinical manifestations are highly variable both in frequency and severity
Genetic determination	autosomal dominant
Prevalence	1/50,000
Function/system disorder	osteo-articular
	dermatology
Type	MCA/MR

Gene product

Name

LIM homeo domain protein (LMX1B)

Mechanism(s)

Gene mutation	Effect	Comments

various types	haploinsufficiency	disruption of DNA binding, of protein stability or of nuclear localization
deletion	haploinsufficiency	diminished transcriptional activity and DNA binding

Remark(s)

extreme variability of the NPS phenotype observed among all different LMX1B mutations challenges the identification of genetic, endogenous, and environmental modifier factors involved in the pathogenesis of NPS

mutation 289delG) within the coding sequence of exon 3 at codon 97, resulting in a frame shift that creates a premature stop at codon 105, causes NPS in a family with variable expressivity of the syndrome, including open angle glaucoma (Milla 2007)

Genotype/Phenotype correlations

an interstitial 9q33.3-q34.1 deletion of 3.07 Mb in size including the genes NR5A1 and LMX1B was detected in a female with XY reversal and ovotestes , evocative of genitopatellar syndrome. No deletion was found in five other GPS patients.