Identification of LMX1B gene point mutations in italian patients affected with Nail-Patella syndrome.

M. Seri, S. Melchionda, S. Dreyer, M. Marini, M. Carella, R. Cusano, M. R. Piemontese, F. Caroli, M. Silengo, L. Zelante, G. Romeo, R. Ravazzolo, P. Gasparini, B. Lee

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Abstract

Nail-Patella syndrome, or osteo-onychodysplasia, is an autosomal dominant disorder characterized by nail dysplasia, absent or hypoplastic patellae, iliac horns and nephropathy. Previous studies have demonstrated linkage of the Nail-Patella locus with polymorphic markers on human chromosome 9q34. Recently, point mutations in the LMX1B gene have been identified in Nail-Patella patients and in families with recurrence of Nail-Patella syndrome and open-angle glaucoma. We describe here the identification of additional point mutations in the LMX1B gene in a set of Italian patients affected with Nail-Patella syndrome: two deletions of 1 and 2 bp causing a frameshift in two sporadic patients and nonsense mutations in two familial and one sporadic cases have been identified. 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. Haplotype analysis in the two familial cases carrying the same stop codon mutation suggests the presence of a founder effect. Finally, analysis of cDNA clones obtained from human fetal kidney has revealed the existence of two different transcripts of LMX1B gene likely due to an alternative splicing.

Original languageEnglish
Pages (from-to)285-290
Number of pages6
JournalInternational Journal of Molecular Medicine
Volume4
Issue number3
Publication statusPublished - Sep 1999

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Nail-Patella Syndrome
Point Mutation
Patella
Nails
Genes
Founder Effect
Homeodomain Proteins
Mutation
Terminator Codon
Nonsense Codon
Open Angle Glaucoma
Alternative Splicing
Human Chromosomes
Horns
Haplotypes
Complementary DNA
Clone Cells
Kidney
Recurrence

ASJC Scopus subject areas

  • Genetics

Cite this

Identification of LMX1B gene point mutations in italian patients affected with Nail-Patella syndrome. / Seri, M.; Melchionda, S.; Dreyer, S.; Marini, M.; Carella, M.; Cusano, R.; Piemontese, M. R.; Caroli, F.; Silengo, M.; Zelante, L.; Romeo, G.; Ravazzolo, R.; Gasparini, P.; Lee, B.

In: International Journal of Molecular Medicine, Vol. 4, No. 3, 09.1999, p. 285-290.

Research output: Contribution to journalArticle

Seri, M, Melchionda, S, Dreyer, S, Marini, M, Carella, M, Cusano, R, Piemontese, MR, Caroli, F, Silengo, M, Zelante, L, Romeo, G, Ravazzolo, R, Gasparini, P & Lee, B 1999, 'Identification of LMX1B gene point mutations in italian patients affected with Nail-Patella syndrome.', International Journal of Molecular Medicine, vol. 4, no. 3, pp. 285-290.
Seri, M. ; Melchionda, S. ; Dreyer, S. ; Marini, M. ; Carella, M. ; Cusano, R. ; Piemontese, M. R. ; Caroli, F. ; Silengo, M. ; Zelante, L. ; Romeo, G. ; Ravazzolo, R. ; Gasparini, P. ; Lee, B. / Identification of LMX1B gene point mutations in italian patients affected with Nail-Patella syndrome. In: International Journal of Molecular Medicine. 1999 ; Vol. 4, No. 3. pp. 285-290.
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