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Appendix A: The Frequency of PKU Mutants from Published Studies

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The content in this publication was current at the time it was published, but it is not being updated. The publication is provided for historical purposes only.​

By Pamela L. Flodman, Erica Ramos, Malia Rumbaugh, M. Anne Spence

Division of Human Genetics, Department of Pediatrics, University of California, Irvine Medical Center, Orange, California

The "Phenylalanine Hydroxylase Locus Knowledgebase," available on the web ( External Web Site Policy), provides detailed information about phenylketonuria and mutations in the phenylalanine hydroxylase gene which produce this genetic disorder. Missing from this website is the frequency of different mutations in different populations. As information becomes available on genotype (mutation) phenotype correlations, the frequency of different mutations will become increasingly important. The panel recognized this deficiency in information and requested that it be assembled, to the extent possible. To this aim, the papers in the extensive bibliography assembled by the staff at the  National Library of Medicine were searched for the key words mutation, frequency, incidence and prevalence. Unfortunately, the abstracts provided for these articles did not always contain the salient facts and so the papers were located in the primary sources and reviewed by one of the authors. Some papers were not available or failed to contain the necessary information even when reviewed in full and could not be included in this summary.

The goal was to provide the frequency information for different populations residing within the United States as determined by systematic surveys. Unfortunately, very few such studies are reported for U.S. populations (their results are summarized in Table A-I). Further, it quickly became apparent that frequency estimates alone would be less than satisfactory since the "populations" surveyed were often quite small and therefore the estimates would have large standard errors. For that reason, it was decided to include the actual sample size for each study and the number of times each mutation was identified. In some studies certain common mutations were assumed to be present and actively tested. Interestingly, however, on a number of occasions these common mutations were not detected. For that reason, a zero appears in the numerator of the reported incidence indicating that these were assayed but not found.

It was not possible to present such a plethora of information in a simple table. Several editorial decisions were made. The data from the U.S. studies are presented in Table A-I . However, since there were not very many of these studies, it was decided that information from other populations, many of which have significant representation in the U.S., would be worth summarizing. This information will prove particularly helpful to cities and states where large populations of these individuals reside and will be very useful as more genotype-phenotype studies are undertaken. The international data are presented in Table A-II, with separate sub tables for five regions.

The symbols used in the two Tables are not self-explanatory. The * indicates each study which reports some information on genotype-phenotype correlation. This information is much too complex to capture in simple tabular form and it is left to the reader to pursue mutations of interest. An # indicates that only haplotype 6 individuals were further tested, an occurrence sufficiently common to note. For some states within the US the results have also been included in larger regional summaries. These are indicated in the Table A-I with a ^. Note that the citation number in parentheses, (n), after each notation in the table refers to the references for the two Tables. A blank box simply indicates that no data were available to us at the time of this summary.

Mutations are listed in the order they occur within the PHE locus. This corresponds exactly to the manner by which data are summarized on the web site and hopefully will assist in correlating information from that source with these appendices. Mutations for which no frequency data were available from any population noted in the literature have been omitted from the tables.

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