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

Abraham Koshy; Roy J Mukkada; Antony P Chettupuzha; Jose V Francis; Julio C Kandathil; Pushpa Mahadevan

doi:10.1016/j.jceh.2019.04.051

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

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

Authors

Abraham Koshy¹, Roy J Mukkada¹, Antony P Chettupuzha¹, Jose V Francis¹, Julio C Kandathil², Pushpa Mahadevan³

Affiliations

¹ Departments of Gastroenterology, VPS Lakeshore Hospital, Kochi, India.
² Radiology, VPS Lakeshore Hospital, Kochi, India.
³ Pathology, VPS Lakeshore Hospital, Kochi, India.

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.