Molecular genetics of cystinuria

Identification of four new mutations and seven polymorphisms, and evidence for genetic heterogeneity

P. Gasparini, M. J. Calonge, L. Bisceglia, J. Purroy, I. Dianzani, A. Notarangelo, F. Rousaud, M. Gallucci, X. Testar, A. Ponzone, Xavier P. Estivill, A. Zorzano, M. Palacin, V. Nunes, L. Zelante

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

A cystinuria disease gene (rBAT) has been recently identified, and some mutations causing the disease have been described. The frequency of these mutations has been investigated in a large sample of 51 Italian and Spanish cystinuric patients. In addition, to identify new mutated alleles, genomic DNA has been analyzed by an accurate and sensitive method able to detect nucleotide changes. Because of the lack of information available on the genomic structure of rBAT gene, the study was carried out using the sequence data so far obtained by us. More than 70% of the entire coding sequence and 8 intron-exon boundaries have been analyzed. Four new mutations and seven intragenic polymorphisms have been detected. All mutations so far identified in rBAT belong only to cystinuria type I alleles, accounting for ~44% of all type I cystinuric chromosomes. Mutation M467T is the most common mutated allele in the Italian and Spanish populations. After analysis of 70% of the rBAT coding region, we have detected normal sequences in cystinuria type II and type III chromosomes. The presence of rBAT mutated alleles only in type I chromosomes of homozygous (type I/I) and heterozygous (type I/III) patients provides evidence for genetic heterogeneity where rBAT would be responsible only for type I cystinuria and suggests a complementation mechanism to explain the intermediate type I/type III phenotype.

Original languageEnglish
Pages (from-to)781-788
Number of pages8
JournalAmerican Journal of Human Genetics
Volume57
Issue number4
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

Cystinuria
Genetic Heterogeneity
Molecular Biology
Alleles
Mutation
Chromosomes
Mutation Rate
Introns
Genes
Exons
Nucleotides
Phenotype
DNA
Population

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Gasparini, P., Calonge, M. J., Bisceglia, L., Purroy, J., Dianzani, I., Notarangelo, A., ... Zelante, L. (1995). Molecular genetics of cystinuria: Identification of four new mutations and seven polymorphisms, and evidence for genetic heterogeneity. American Journal of Human Genetics, 57(4), 781-788.

Molecular genetics of cystinuria : Identification of four new mutations and seven polymorphisms, and evidence for genetic heterogeneity. / Gasparini, P.; Calonge, M. J.; Bisceglia, L.; Purroy, J.; Dianzani, I.; Notarangelo, A.; Rousaud, F.; Gallucci, M.; Testar, X.; Ponzone, A.; Estivill, Xavier P.; Zorzano, A.; Palacin, M.; Nunes, V.; Zelante, L.

In: American Journal of Human Genetics, Vol. 57, No. 4, 1995, p. 781-788.

Research output: Contribution to journalArticle

Gasparini, P, Calonge, MJ, Bisceglia, L, Purroy, J, Dianzani, I, Notarangelo, A, Rousaud, F, Gallucci, M, Testar, X, Ponzone, A, Estivill, XP, Zorzano, A, Palacin, M, Nunes, V & Zelante, L 1995, 'Molecular genetics of cystinuria: Identification of four new mutations and seven polymorphisms, and evidence for genetic heterogeneity', American Journal of Human Genetics, vol. 57, no. 4, pp. 781-788.
Gasparini, P. ; Calonge, M. J. ; Bisceglia, L. ; Purroy, J. ; Dianzani, I. ; Notarangelo, A. ; Rousaud, F. ; Gallucci, M. ; Testar, X. ; Ponzone, A. ; Estivill, Xavier P. ; Zorzano, A. ; Palacin, M. ; Nunes, V. ; Zelante, L. / Molecular genetics of cystinuria : Identification of four new mutations and seven polymorphisms, and evidence for genetic heterogeneity. In: American Journal of Human Genetics. 1995 ; Vol. 57, No. 4. pp. 781-788.
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