A spectrum of LMX1B mutations in Nail-Patella syndrome: new point mutations, deletion, and evidence of mosaicism in unaffected parents

Marini, Monica; Bocciardi, Renata; Gimelli, Stefania; Di Duca, Marco; Divizia, Maria T.; Baban, Anwar; Gaspar, Harald; Mammi, Isabella; Garavelli, Livia; Cerone, Roberto; Emma, Francesco; Bedeschi, Maria F.; Tenconi, Romano; Sensi, Alberto; Salmaggi, Andrea; Bengala, Mario; Mari, Francesca; Colussi, Gianluca; Szczaluba, Krzysztof; Antonarakis, Stylianos; Seri, Marco; Lerone, Margherita; Ravazzolo, Roberto

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Title		A spectrum of LMX1B mutations in Nail-Patella syndrome: new point mutations, deletion, and evidence of mosaicism in unaffected parents
Authors		Marini, Monica Bocciardi, Renata Gimelli, Stefania Di Duca, Marco Divizia, Maria T. Baban, Anwar Gaspar, Harald Mammi, Isabella Garavelli, Livia Cerone, Roberto Emma, Francesco Bedeschi, Maria F. Tenconi, Romano Sensi, Alberto Salmaggi, Andrea Bengala, Mario Mari, Francesca Colussi, Gianluca Szczaluba, Krzysztof Antonarakis, Stylianos Seri, Marco Lerone, Margherita Ravazzolo, Roberto show all authors [1 - 23]
Published in		Genetics in Medicine. 2010, vol. 12, no. 7, p. 431-439
Abstract		PURPOSE: 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. CONCLUSION: The study of the described case series provides some original observations in an "old" genetic disorder.
Keywords		Child — Chromosome Deletion — Chromosomes, Human, Pair 9/genetics — Comparative Genomic Hybridization — Female — Homeodomain Proteins/genetics — Humans — LIM-Homeodomain Proteins — Male — Mosaicism — Nail-Patella Syndrome/genetics — Oligonucleotide Array Sequence Analysis — Parents — Pedigree — Point Mutation/genetics — Polymerase Chain Reaction — Polymorphism, Single Nucleotide — Prognosis — Transcription Factors/genetics
Identifiers		DOI: 10.1097/GIM.0b013e3181e21afa PMID: 20531206
Full text		Article - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement
Research group		Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
Citation (ISO format)		MARINI, Monica et al. A spectrum of LMX1B mutations in Nail-Patella syndrome: new point mutations, deletion, and evidence of mosaicism in unaffected parents. In: Genetics in Medicine, 2010, vol. 12, n° 7, p. 431-439. https://archive-ouverte.unige.ch/unige:21111