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Eur J Haematol. 2017 Mar;98(3):228-234. doi: 10.1111/ejh.12820. Epub 2016 Nov 11.

Clinical evaluation of a hemochromatosis next-generation sequencing gene panel.

Author information

1
Department of Medicine, McMaster University, Hamilton, ON, Canada.
2
Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada.
3
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
4
Department of Medicine, Western University, London, ON, Canada.

Abstract

BACKGROUND:

Next-generation sequencing of an iron metabolism gene panel could identify pathogenic mutations, improving on standard hemochromatosis genetic testing and providing a molecular diagnosis in patients with suspected iron overload.

METHODS:

A next-generation sequencing panel of 15 genes with known roles in iron metabolism was constructed. A total of 190 patients were sequenced: 94 from a tertiary hemochromatosis clinic and 96 submitted for HFE testing with biochemical evidence of iron overload [elevated ferritin (>450 μg/L) or transferrin saturation (>55%)] obtained from a chart review.

RESULTS:

From the hemochromatosis clinic cohort, six patients were diagnosed with non-HFE hemochromatosis due to homozygous hemojuvelin (HFE2) mutations. Ten additional heterozygous pathogenic mutations were observed. From the chart review cohort, a C-terminus ferritin light chain (FTL) frameshift mutation was observed consistent with neuroferritinopathy. Heterozygous deletion of HFE2 and four additional rare pathogenic or likely pathogenic heterozygous mutations were identified in seven patients.

CONCLUSIONS:

An iron metabolism gene panel provided a molecular diagnosis in six patients with non-HFE iron overload and is suitable for diagnostic purposes in exceptional cases in specialized clinics. Further research will be required to assess the modifier effect of rare heterozygous mutations in iron metabolism genes.

KEYWORDS:

hemochromatosis; iron overload; neuroferritinopathy; next-generation sequencing

PMID:
27753142
DOI:
10.1111/ejh.12820
[Indexed for MEDLINE]

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