PMID: 8592329Nov 1, 1995Paper

Discordant phenylketonuria phenotypes in one family: the relationship between genotype and clinical outcome is a function of multiple effects

Journal of Medical Genetics
L A TyfieldL P Hunt

Abstract

Four members spanning three generations of one family have phenylketonuria of varying degrees of severity. Two first cousins were screened in the neonatal period and have had dietary phenylalanine restriction since diagnosis, the older patient having been classified as having more severe PKU and the younger one as having mild PKU. Their mutual grandfather and his older brother also have a significant hyperphenylalaninaemia and are of normal intelligence despite never having had restricted phenylalanine intake. Mutation analysis of the phenylalanine hydroxylase (PAH) gene has established that there are four different mutations, two in exon 2 (F39L and L48S) and two in exon 3 (R111X and S67P), which give rise to PKU in this family. In order to establish their relative severity, we screened the PKU populations of western Scotland and the south west of England for these mutations. The exon 3 mutations are rare; however, F39L is relatively common in Scotland and L48S in England. A comparison of diagnostic blood phenylalanine concentrations in subjects carrying L48S/null or F39L/null mutations with those carrying two null mutations suggest that these exon 2 mutations are less deleterious. Thus, in this family, the different biochemic...Continue Reading

References

Sep 1, 1990·Journal of Medical Genetics·L A TyfieldP S Harper
May 2, 1991·The New England Journal of Medicine·Y OkanoH Lou
Mar 1, 1991·European Journal of Pediatrics·Y OkanoS L Woo
Feb 1, 1988·Human Genetics·D N Cooper, H Youssoufian
Dec 1, 1994·Acta Paediatrica. Supplement·B PérezM Ugarte
May 1, 1993·Journal of Medical Genetics·S J RamusR G Cotton

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Citations

Mar 22, 2013·Journal of Human Genetics·María A BuenoMaría L Couce
Jul 27, 2015·Clinica Chimica Acta; International Journal of Clinical Chemistry·Roberta TrunzoMaurizio Margaglione
Aug 1, 1997·American Journal of Human Genetics·P B MunroeS E Mole
Nov 21, 1998·The Journal of Nervous and Mental Disease·J E Rall
Jun 27, 2009·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Sofia BouchlariotouGeorge Maroulis
May 26, 2004·Journal of Inherited Metabolic Disease·J J JohnstonL-J C Wong

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