Journal ArticleDOI
Double mutant alleles: are they rare?
Alexey Savov,Dora Angelicheva,A Balassopoulou,Albena Jordanova,S Noussia-Arvanitakis,Luba Kalaydjieva +5 more
TLDR
The presence of two different mutations carried by the same CF allele has been demonstrated in four out of 44 Bulgarian CF patients during a systematic search of the entire coding sequence of the CFTR gene, suggesting that double mutant alleles may be more common than expected and could account for some of the problems in phenotype-genotype correlations.Abstract:
The presence of two different mutations carried by the same CF allele has been demonstrated in four out of 44 Bulgarian CF patients during a systematic search of the entire coding sequence of the CFTR gene. Two of the double mutant alleles include one nonsense and one missense mutation and although the nonsense mutation can be considered to be the main defect, the amino acid substitutions are good candidates for disease-causing mutations as well. One double mutant carries two missense mutations whose contribution to the CF phenotype is difficult to evaluate. The findings suggest that double mutant alleles may be more common than expected and could account for some of the problems in phenotype-genotype correlations. Such alleles may have important implications for molecular diagnosis and genetic counselling.read more
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Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans.
TL;DR: The findings suggest that in humans, as in other mammals, the MC1R is a control point in the regulation of pigmentation phenotype and, more importantly, that variations in this protein are associated with a poor tanning response.
Journal ArticleDOI
Human thiopurine methyltransferase pharmacogenetics: Gene sequence polymorphisms
Diane M. Otterness,Carol L. Szumlanski,Lynne Lennard,B. Klemetsdal,Jarle Aarbakke,Jeong Ok Park-Hah,Heiko Iven,Kjeld Schmiegelow,Earl L. Branum,John T. O'Brien,Richard M. Weinshilboum +10 more
TL;DR: Characterization of variant alleles for low TPMT enzyme activity will help make it possible to assess the potential clinical utility of deoxyribonucleic acid‐based diagnostic tests for determining T PMT genotype.
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Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2).
TL;DR: It is established that SLC10A2 mutations can cause primary bile acid malabsorption and underscore the ileal Na+/bile acid cotransporter's role in intestinal reclamation of bile acids.
Journal ArticleDOI
A European Multicenter Study of Phenylalanine Hydroxylase Deficiency: Classification of 105 Mutations and a General System for Genotype-Based Prediction of Metabolic Phenotype
Per Guldberg,Françoise Rey,Johannes Zschocke,Valentino Romano,Baudouin François,Luc Michiels,Kurt Ullrich,Georg F. Hoffmann,Peter Burgard,H. Schmidt,Concetta Meli,Enrica Riva,Irma Dianzani,Alberto Ponzone,Jean Rey,Flemming Güttler +15 more
TL;DR: The classification of 105 PAH mutations may allow the prediction of the biochemical phenotype in >10,000 genotypes, which may be useful for the management of hyperphenylalaninemia in newborns.
Journal ArticleDOI
Cystathionine β‐synthase mutations in homocystinuria
Jan P. Kraus,Miroslav Janosik,Viktor Kožich,Roseann Mandell,Vivian E. Shih,Maria Pia Sperandeo,Gianfranco Sebastio,Raffaella de Franchis,Generoso Andria,Leo A. J. Kluijtmans,Henk J. Blom,Godfried H.J. Boers,Ross B. Gordon,Pierre Kamoun,Michael Y. Tsai,Warren D. Kruger,Hans G. Koch,Toshihiro Ohura,Mette Gaustadnes +18 more
TL;DR: Ninety‐two different disease‐associated mutations have been identified in the CBS gene in 310 examined homocystinuric alleles in more than a dozen laboratories around the world, and most of these mutations are missense, and the vast majority of these are private mutations.