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. 2020 Mar-Apr;10(2):163-169.
doi: 10.1016/j.jceh.2019.04.051. Epub 2019 Apr 29.

Hemochromatosis in India: First Report of Whole Exome Sequencing With Review of the Literature

Abraham Koshy  1 , Roy J Mukkada  1 , Antony P Chettupuzha  1 , Jose V Francis  1 , Julio C Kandathil  2 , Pushpa Mahadevan  3
Affiliations

Hemochromatosis in India: First Report of Whole Exome Sequencing With Review of the Literature

Abraham Koshy et al. J Clin Exp Hepatol. 2020 Mar-Apr.

Abstract

Background: Primary hemochromatosis is unusual in India. The homeostatic iron regulator (HFE) gene C282Y mutation, a common cause for hemochromatosis in Europe, is considered almost nonexistent in India. We are reporting a case of hemochromatosis with the HFE gene C282Y mutation and two other adult cases with a novel hemojuvelin (HJV) mutation from Kerala.

Methods: Of 434 cases with chronic liver disease, 3 cases were identified with the serum ferritin level of more than 1000 ng/mL and primary hemochromatosis after excluding secondary causes. Whole exome sequencing, including genes HFE, HJV, SLC40A1, TFR2, FTH1, HAMP, SKIV2L, TTC37, and BMP2, was performed for blood samples in all 3 cases.

Results: One patient with hemochromatosis had a homozygous HFE gene C282Y mutation, and two other adult cases had a novel homozygous HJV D355Y mutation. This is the first report of hemochromatosis associated with the HFE C282Y mutation from Kerala and the second report in India. This is the second report of hemochromatosis associated with an HJV mutation from India.

Conclusion: HJV mutations may explain some of the adult onset primary hemochromatosis in India.

Keywords: 1D, single-dimensional; 3D, three-dimensional; ACMG, American College of Medical Genetics; ExAC, Exome Aggregation Consortium; HFE, homeostatic iron regulator; HJV, hemojuvelin; Polyphen2, Polymorphism Phenotyping v2; SIFT, Sorting Intolerant from Tolerant; cirrhosis; diabetes; gene; gnomAD, Genome Aggregation Database; iron; juvenile.

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Figures

Figure 1
Figure 1
Patient cohort with cirrhosis and high serum ferritin in whom the genetic test was performed. HFE, homeostatic iron regulator. WES, whole exome sequencing.
Figure 2
Figure 2
Course of parameters in case 1 over 10 years.
Figure 3
Figure 3
Family tree of patient 2.II.3, the proband.
Figure 4
Figure 4
Cartoon of HJV 1D structure with known mutations., , , , , , , 1D, single-dimensional; HJV, hemojuvelin.
See this image and copyright information in PMC

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