We report the characterization of eight mutations of sterol 27-hydroxylase gene (CYP27) in five Italian patients with cerebrotendinous xanthomatosis, who were found to be compound heterozygotes. Four mutations (C --> T at nt 45 of exon 4, G(+1) --> A in intron 6, G(+5) --> T in intron 7, and G(-1) --> A in intron 7) are novel. The C --> T at nt 45 of exon 4 converts the arginine codon into a stop codon thus generating a truncated protein of 198 amino acids. The three splice site mutations reduced the content of CYP27 mRNA in skill fibroblasts to very low or undetectable levels and generated minute amounts of abnormal mRNAs. The G(+1) --> A transition in intron 6 produced three abnormal mRNAs. In the first, the 5' half of exon 6 joins to exon 7, skipping 89 bp of exon 6, and in the second, exon 5 joins directly to exon 7. The predicted translation products of these mRNAs are truncated proteins. In the third abnormal mRNA, exon 5 joins to exon 8 with an in-frame deletion of 246 bp. The G(+5) --> T transversion in intron 7 generates a single abnormal mRNA in which exon 6 joins directly to exon 8, with a frameshift and a premature stop codon. In the G(-1) --> A transition in intron 7, two mRNAs are generated. In the first, the retention of the whole intron 7 causes a frameshift and a premature stop codon; in the second, the joining of exon 7 to exon 8 is associated with an in-frame deletion of the first 6 nucleotides. All these novel mutations are predicted to produce structurally abnormal enzymatic proteins with no measurable biological activity.

Four novel mutations of sterol 27-hydroxylase gene in Italian patients with cerebrotendinous xanthomatosis / R., Garuti; M. A., Croce; Tiozzo, Roberta; M. T., Dotti; A., Federico; S., Bertolini; CALANDRA BUONAURA, Sebastiano. - In: JOURNAL OF LIPID RESEARCH. - ISSN 0022-2275. - 38:(1997), pp. 2322-2334.

Four novel mutations of sterol 27-hydroxylase gene in Italian patients with cerebrotendinous xanthomatosis

TIOZZO, Roberta;CALANDRA BUONAURA, Sebastiano
1997

Abstract

We report the characterization of eight mutations of sterol 27-hydroxylase gene (CYP27) in five Italian patients with cerebrotendinous xanthomatosis, who were found to be compound heterozygotes. Four mutations (C --> T at nt 45 of exon 4, G(+1) --> A in intron 6, G(+5) --> T in intron 7, and G(-1) --> A in intron 7) are novel. The C --> T at nt 45 of exon 4 converts the arginine codon into a stop codon thus generating a truncated protein of 198 amino acids. The three splice site mutations reduced the content of CYP27 mRNA in skill fibroblasts to very low or undetectable levels and generated minute amounts of abnormal mRNAs. The G(+1) --> A transition in intron 6 produced three abnormal mRNAs. In the first, the 5' half of exon 6 joins to exon 7, skipping 89 bp of exon 6, and in the second, exon 5 joins directly to exon 7. The predicted translation products of these mRNAs are truncated proteins. In the third abnormal mRNA, exon 5 joins to exon 8 with an in-frame deletion of 246 bp. The G(+5) --> T transversion in intron 7 generates a single abnormal mRNA in which exon 6 joins directly to exon 8, with a frameshift and a premature stop codon. In the G(-1) --> A transition in intron 7, two mRNAs are generated. In the first, the retention of the whole intron 7 causes a frameshift and a premature stop codon; in the second, the joining of exon 7 to exon 8 is associated with an in-frame deletion of the first 6 nucleotides. All these novel mutations are predicted to produce structurally abnormal enzymatic proteins with no measurable biological activity.
1997
38
2322
2334
Four novel mutations of sterol 27-hydroxylase gene in Italian patients with cerebrotendinous xanthomatosis / R., Garuti; M. A., Croce; Tiozzo, Roberta; M. T., Dotti; A., Federico; S., Bertolini; CALANDRA BUONAURA, Sebastiano. - In: JOURNAL OF LIPID RESEARCH. - ISSN 0022-2275. - 38:(1997), pp. 2322-2334.
R., Garuti; M. A., Croce; Tiozzo, Roberta; M. T., Dotti; A., Federico; S., Bertolini; CALANDRA BUONAURA, Sebastiano
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/306850
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 38
  • ???jsp.display-item.citation.isi??? 29
social impact