The genetic and biochemical basis of trimethylaminuria in an Irish cohort
| Autor: | Gregory M. Pastores, Mandy Nesbitt, James J. O’Byrne, Niall Byrne, Zaza Abidin, Richard Kirk, Eileen P. Treacy, Samantha Doyle, Daniel N. Murphy |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Research Report
Endocrinology Diabetes and Metabolism genotype Population Trimethylamine N-oxide FMO3 gene QH426-470 Biochemistry Genetics and Molecular Biology (miscellaneous) Genetic analysis Diseases of the endocrine glands. Clinical endocrinology chemistry.chemical_compound Genotype Internal Medicine medicine Genetics genetic polymorphism education Genetic testing trimethylamine N‐oxide education.field_of_study medicine.diagnostic_test business.industry Haplotype Genetic disorder Research Reports medicine.disease RC648-665 chemistry fish odor syndrome Cohort trimethylamine business |
| Zdroj: | JIMD Reports JIMD Reports, Vol 47, Iss 1, Pp 35-40 (2019) |
| ISSN: | 2192-8312 2192-8304 |
| Popis: | Background Inherited trimethylaminuria (TMAU), a rare genetic disorder of hepatic metabolism of trimethylamine (TMA) causing excessive accumulation of malodorous trimethylamine (TMA), is a socially distressing disorder. Diagnosis is made by biochemical analysis of urine, with the calculation of flavin monooxygenase trimethylamine conversion capacity. Genetic testing, sequencing the entire coding region of the FMO3 gene has been recommended for affected individuals who convert less than 90% of the total TMA load to TMAO. Methods Genetic analysis was undertaken for 13 Irish patients with TMAU of varying phenotypic severity (three severe, six moderate, and four mild). Results A genetic diagnosis was made for seven patients, including for five of the nine moderate to severely affected cases. We noted the c.913G>T;p.(Glu305*) and c.458C>T;p.(Pro153Leu) mutations in this Irish population with severe TMAU which is consistent with our earlier findings in Australian and North American families of Irish and British descent. Three individuals were noted to be homozygous for the common variant haplotype c.472G>A;923A>G;p.(Glu158Lys);(Glu308Gly). We also identified three novel variants in this population, which are likely to be pathogenic: c.682G>A;p(Gly228Ser), c.694G>T:p(Asp232Tyr), and c.989G>A;p.(Gly330Glu). Conclusion Urinary biochemical analysis probably remains the first line diagnostic approach to classify the various types of TMAU. FMO3 gene analysis is likely only to be informative for certain presentations of TMAU. |
| Databáze: | OpenAIRE |
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