Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

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

References

    1. Trujillano D., Bertoli-Avella A.M., Kumar K.K. Clinical exome sequencing: results from 2819 samples reflecting 1000 families. Eur J Hum Genet. 2017;25:176–182. - PMC - PubMed
    1. Dhillon B.K., Das R., Garewal G. Frequency of primary iron overload and HFE gene mutations (C282Y, H63D and S65C) in chronic liver disease patients in north India. World J Gastroenterol. 2007;13:2956–2959. - PMC - PubMed
    1. Thakur V., Guptan R.C., Hashmi A.Z., Sakhuja P., Malhotra V., Sarin S.K. Absence of hemochromatosis associated Cys282Tyr HFE gene mutation and low frequency of hemochromatosis phenotype in nonalcoholic chronic liver disease patients in India. J Gastroenterol Hepatol. 2004;19:86–90. - PubMed
    1. Jain S., Agarwal S., Tamhankar P., Verma P., Choudhuri G. Lack of association of primary iron overload and common HFE gene mutations with liver cirrhosis in adult Indian population. Indian J Gastroenterol. 2011;30:161–165. - PubMed
    1. Athiyarath R., Srivastava A., Edison E.S. Molecular basis of primary iron overload in India and the role of serum-derived factors in hepcidin regulation. Ann Hematol. 2013;92:843–844. - PubMed