Prevalence of Hfe Mutations in California Newborns

Hoppe, Carolyn; Watson, Robert H.; Long, Christopher M.; Lorey, Fred; Lara, Robles; Klitz, William; Styles, Lori; Vichinsky, Elliott

doi:10.1080/08880010600751918

Cited by 9 publications

(5 citation statements)

References 61 publications

(66 reference statements)

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“… 48 Subsequent case–control studies have reported a median p.C282Y/p.H63D compound heterozygous genotype frequency among clinically characterized hemochromatosis cohorts of 4.6% (0–21.7%), 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 which is significantly higher than the compound heterozygote frequency of 1.7% (0–7.7%) reported in screening studies. 60 , 63 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 ,...…”

Section: Methodology and Resultsmentioning

confidence: 99%

EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH)

et al. 2015

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Molecular genetic testing for hereditary hemochromatosis (HH) is recognized as a reference test to confirm the diagnosis of suspected HH or to predict its risk. The vast majority (typically >90%) of patients with clinically characterized HH are homozygous for the p.C282Y variant in the HFE gene, referred to as HFE-related HH. Since 1996, HFE genotyping was implemented in diagnostic algorithms for suspected HH, allowing its early diagnosis and prevention. However, the penetrance of disease in p.C282Y homozygotes is incomplete. Hence, homozygosity for p.C282Y is not sufficient to diagnose HH. Neither is p.C282Y homozygosity required for diagnosis as other rare forms of HH exist, generally referred to as non-HFE-related HH. These pose significant challenges when defining criteria for referral, testing protocols, interpretation of test results and reporting practices. We present best practice guidelines for the molecular genetic diagnosis of HH where recommendations are classified, as far as possible, according to the level and strength of evidence. For clarification, the guidelines' recommendations are preceded by a detailed description of the methodology and results obtained with a series of actions taken in order to achieve a wide expert consensus, namely: (i) a survey on the current practices followed by laboratories offering molecular diagnosis of HH; (ii) a systematic literature search focused on some identified controversial topics; (iii) an expert Best Practice Workshop convened to achieve consensus on the practical recommendations included in the guidelines.

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Section: Methodology and Resultsmentioning

confidence: 99%

EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH)

et al. 2015

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“…In 2002, DNA was extracted from punches from 4000 blood cards using QiaAmp 96 DNA Blood kits (Qiagen, Valencia, CA) in a 96-well block extractor per manufacturers instructions[3]. Cards were not sorted by ethnicity prior to DNA preparation; thus, African American samples were distributed at random among the total sample set[4].…”

Section: Methodsmentioning

confidence: 99%

Concordance of next generation sequence-based and sequence specific oligonucleotide probe-based HLA-DRB1 genotyping

Lane¹,

Johnson

Noble³

2015

Human Immunology

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Next generation sequencing (NGS) of clonally amplified DNA, using Roche 454 technology, was used to genotype HLA-DRB1, DRB3, DRB4, and DRB5 loci (exon 2 only) from a set of 993 samples from newborns with maternally-reported African American ancestry. DRB1 exon 2 was genotyped previously on the same sample set using sequence-specific oligonucleotide probe (SSOP) technology. Comparison of the genotype calls from both methods indicated concordance of 92.3%. Some discordance was expected due to the higher resolution of NGS data, compared to SSOP data. This resulted from selection of the incorrect allele from the ambiguity string produced by SSOP genotyping. Of 76 discordant genotypes, only three were due to resolution of ambiguity with the NGS method. The low percent of changes due to the increased resolution of the NGS method instills confidence in the overall value of previous data genotyped with moderate resolution methods, i.e., the vast majority of alleles present in a population are those that are detectable at moderate resolution. The remaining 73 discordant genotypes resulted from preventable errors in sample handling, data interpretation, and data entry. These results underscore the potential for error that can result from factors such as low quality genomic DNA, manual data entry, and interpretation of marginal genotyping results. Optimization of genomic DNA quality, automation of genotyping steps wherever possible, and use of the highest resolution technology available can lead to dramatic improvements in HLA genotype data quality. NGS-based methodology generated data of superior quality and accuracy compared to the SSOP system.

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“…Advanced read-out Mass spectrometry based, capillary electrophoresis, chip based n/a n/a n/a + [174][175][176][177][178][179] Reverse hybridization assay Multiplex PCR amplification followed by reverse hybridization n/a n/a n/a + [21,150,180,181] Novel extraction methods Dried blood spots, whole-blood PCR n/a n/a n/a ++ [38,158,182] Whether they are screened with the above procedure depends upon their age, health status, and the attitude of the family.…”

Section: Family Screeningmentioning

confidence: 99%

EASL clinical practice guidelines for HFE hemochromatosis

Ji-don¹

2010

Journal of Hepatology

480

167

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Iron overload in humans is associated with a variety of genetic and acquired conditions. Of these, HFE hemochromatosis (HFE-HC) is by far the most frequent and most well-defined inherited cause when considering epidemiological aspects and risks for iron-related morbidity and mortality. The majority of patients with HFE-HC are homozygotes for the C282Y polymorphism [1]. Without therapeutic intervention, there is a risk that iron overload will occur, with the potential for tissue damage and disease. While a specific genetic test now allows for the diagnosis of HFE-HC, the uncertainty in defining cases and disease burden, as well as the low phenotypic penetrance of C282Y homozygosity poses a number of clinical problems in the management of patients with HC. This Clinical Practice Guideline will therefore, focus on HFE-HC, while rarer forms of genetic iron overload recently attributed to pathogenic mutations of transferrin receptor 2, (TFR2), hepcidin (HAMP), hemojuvelin (HJV), or to a sub-type of ferroportin (FPN) mutations, on which limited and sparse clinical and epidemiologic data are available, will not be discussed. We have developed recommendations for the screening, diagnosis, and management of HFE-HC.

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Prevalence of Hfe Mutations in California Newborns

Cited by 9 publications

References 61 publications

EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH)

EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH)

Concordance of next generation sequence-based and sequence specific oligonucleotide probe-based HLA-DRB1 genotyping

EASL clinical practice guidelines for HFE hemochromatosis

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