A spectrum of LMX1B mutations in Nail-Patella syndrome: new point mutations, deletion, and evidence of mosaicism in unaffected parents.
OBJECTIVE
Nail-Patella syndrome (MIM 161200) is a rare autosomal dominant disorder characterized by hypoplastic or absent patellae, dystrophic nails, dysplasia of the elbows, and iliac horn. In 40% of cases, a glomerular defect is present and, less frequently, ocular damage is observed. Inter- and intrafamilial variable expressivity of the clinical phenotype is a common finding. Mutations in the human LMX1B gene have been demonstrated to be responsible for Nail-Patella syndrome in around 80% of cases.


METHODS
Standard polymerase chain reaction and sequencing methods were used for mutation and single nucleotide polymorphism identification and control of cloned sequences. Array-CGH (Agilent, 244A Kit) was used for detection of deletions. Standard cloning techniques and the Snapshot method were used for analysis of mosaicism.


RESULTS
In this study, we present the results of LMX1B screening of 20 Nail-Patella syndrome patients. The molecular defect was found in 17 patients. We report five novel mutations and a approximately 2 Mb deletion in chromosome 9q encompassing the entire LMX1B gene in a patient with a complex phenotype. We present evidence of somatic mosaicism in unaffected parents in two cases, which, to our knowledge, are the first reported cases of inheritance of a mutated LMX1B allele in Nail-Patella syndrome patients from a mosaic parent.


CONCLUSIONS
The study of the described case series provides some original observations in an "old" genetic disorder.
Marini
Monica
M
Molecular Genetics and Cytogenetics Unit, G Gaslini Institute, Genova, Italy.
Bocciardi
Renata
R
Gimelli
Stefania
S
Di Duca
Marco
M
Divizia
Maria T
MT
Baban
Anwar
A
Gaspar
Harald
H
Mammi
Isabella
I
Garavelli
Livia
L
Cerone
Roberto
R
Emma
Francesco
F
Bedeschi
Maria F
MF
Tenconi
Romano
R
Sensi
Alberto
A
Salmaggi
Andrea
A
Bengala
Mario
M
Mari
Francesca
F
Colussi
Gianluca
G
Szczaluba
Krzysztof
K
Antonarakis
Stylianos E
SE
Seri
Marco
M
Lerone
Margherita
M
Ravazzolo
Roberto
R
D002648:Child; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008297:Male; D009030:Mosaicism; D009261:Nail-Patella Syndrome / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010290:Parents; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*
D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors