Heterozygosity for an exon 12 splicing mutation and a W234G missense mutation in an American child with chronic tyrosinemia type 1

✍ Scribed by Si Houn Hahn; Donna Krasnewich; Mark Brantly; Eli Anne Kvittingen; William A. Gahl

• Book ID: 102860915
• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 719 KB
• Volume: 6
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1380060113

✦ Synopsis

Hereditary tyrosinemia type 1, an autosomal recessive disorder caused by deficiency of fumarylacetoacetate hydrolase (FAH), manifests in either an acute or a chronic form. We used reverse transcription and the polymerase chain reaction to amplify the FAH cDNA of a 12-year-old American boy with chronic tyrosinemia type 1. The patient is a compound heterozygote for mutations in the FAH gene. One allele contains a missense mutation in codon 234 changing a tryptophan to a glycine; this allele was of maternal origin. Mutagenesis and transfection into COS cells demonstrated that the W234G mutation abolishes FAH activity. The patient's paternally derived allele is a splicing mutation in the + 5 position of intron 12, causing either insertion of a 105 bp fragment due to a cryptic splice site, or skipping of exon 12, or skipping of both exons 12 and 13. The chronic phenotype of tyrosinemia type 1 in this patient may be due to some residual, correct splicing by the allele with the splicing mutation.