Novel splice-affecting variants in CYP27A1 gene in two Chilean patients with Cerebrotendinous Xanthomatosis
| Autor: | Javier Campión, José Luis Santos, Javier Andrés Vega, Alberto Maiz, Susan V. Smalley, Carlos F. Lagos, J. Alfredo Martínez, Yudith Preiss, Enzo Rivera, José Suazo, Isidora Angellotti, Karin Kleinsteuber |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Genetics
Mutation lcsh:QH426-470 Cerebrotendinous Xanthomatosis Biology medicine.disease_cause Compound heterozygosity Molecular biology Exon skipping chemistry.chemical_compound Exon lcsh:Genetics splicing chemistry Chenodeoxycholic acid CYP27A1 Human and Medical Genetics medicine mutation Molecular Biology Gene exon skipping |
| Zdroj: | Genetics and Molecular Biology Genetics and Molecular Biology v.38 n.1 2015 Sociedade Brasileira de Genética (SBG) instacron:SBG Genetics and Molecular Biology, Vol 38, Iss 1, Pp 30-36 (2015) Genetics and Molecular Biology, Volume: 38, Issue: 1, Pages: 30-36, Published: MAR 2015 |
| ISSN: | 1678-4685 1415-4757 |
| Popis: | Cerebrotendinous Xanthomatosis (CTX), a rare lipid storage disorder, is caused by recessive loss-of-function mutations of the 27-sterol hydroxylase (CYP27A1), producing an alteration of the synthesis of bile acids, with an accumulation of cholestanol. Clinical characteristics include juvenile cataracts, diarrhea, tendon xanthomas, cognitive impairment and other neurological manifestations. Early diagnosis is critical, because treatment with chenodeoxycholic acid may prevent neurological damage. We studied the CYP27A1 gene in two Chilean CTX patients by sequencing its nine exons, exon-intron boundaries, and cDNA from peripheral blood mononuclear cells. Patient 1 is a compound heterozygote for the novel substitution c.256-1G > T that causes exon 2 skipping, leading to a premature stop codon in exon 3, and for the previously-known pathogenic mutation c.1183C > T (p.Arg395Cys). Patient 2 is homozygous for the novel mutation c.1185-1G > A that causes exon 7 skipping and the generation of a premature stop codon in exon 8, leading to the loss of the crucial adrenoxin binding domain of CYP27A1. |
| Databáze: | OpenAIRE |
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