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    Klinika Obstetrike Gjinekologjike Alushani
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    The DNA sample from patient Ersen Spahija was analyzed through whole exome sequencing. Two heterozygous variants were detected in the HFE gene. The first, c.187 C>G (p.His63Asp), is a known pathogenic variant. The second, c.340+4 T>C, is registered as likely benign but has been shown to cause iron accumulation when present together with the p.His63Asp variant. Publishing this case could provide useful information for future patients who have these same two variants detected. Permission from the patient would be required for publication.

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    The DNA sample from patient Ersen Spahija was analyzed through whole exome sequencing. Two heterozygous variants were detected in the HFE gene. The first, c.187 C>G (p.His63Asp), is a known pathogenic variant. The second, c.340+4 T>C, is registered as likely benign but has been shown to cause iron accumulation when present together with the p.His63Asp variant. Publishing this case could provide useful information for future patients who have these same two variants detected. Permission from the patient would be required for publication.

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    © All Rights Reserved
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    7 views2 pages

    Screenshot 2022-12-08 (20.30.31)

    Uploaded by

    Klinika Obstetrike Gjinekologjike Alushani
    The DNA sample from patient Ersen Spahija was analyzed through whole exome sequencing. Two heterozygous variants were detected in the HFE gene. The first, c.187 C>G (p.His63Asp), is a known pathogenic variant. The second, c.340+4 T>C, is registered as likely benign but has been shown to cause iron accumulation when present together with the p.His63Asp variant. Publishing this case could provide useful information for future patients who have these same two variants detected. Permission from the patient would be required for publication.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
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    of 2

    29.11.

    2022

    Dear Dr,

    DNA isolation was performed from the peripheral blood sample of your patient Ersen
    Spahija. The DNA sample was transferred to the laboratory of our partner Neuberg Genomic
    Medicine Center in the United States and analyzed by whole exome sequencing-WES with NGS
    method.

    A total of 9 GB of data was created and bioinformatics analysis was performed by sequencing
    8 genes that may be related to clinical data with 100% coverage. In the HFE gene responsible for
    hemochromatosis, 1 'pathogenic' and 1 'likely benign' variant was detected in heterozygous form.
    Almost all of the kits available in the market for hemochromatosis disease target the p.H63D,
    p.C282Y and p.S65C pathogenic variants that are frequently detected in patients. For this reason,
    there are cases that have clinical data using real-time PCR-based kits in the past years, but only one
    of these 3 variants was found to be heterozygous, and the situation could not be clarified genetically.
    If studied by sequencing, there is the possibility of detecting an additional heterozygous variant as in
    this case.
    Pathogenic c.187 C>G (p.His63Asp, p.H63D) variant was found heterozygous in your patient
    and a second variant c.340+4 T>C heterozygote was detected. This variant (rs2071303) is registered
    as 'likely benign' in the ClinVar database. There are also studies reporting polymorphism (de Lucas AP
    et al 2005, PMID: 2071303). c.340+4 T>C is a splice site variant. Removal of exon 2 by mis-splicing can
    result in a protein missing the alpha 1 domain, which is required for HFE/transferrin receptor-1
    interactions. Branco CC et al (2015, PMID: 26501199) found that heterozygous c.340+4 T>C variant
    (positive in 74.3% of patients) was transmitted together with heterozygous c.187 C>G (p.His63Asp,
    p.H63D) in patients with Hemochromatosis on the island of Sao Miguel. They reported iron
    accumulation. The last sentence of the published study is 'this data needs to be verified in other
    societies'. Six months ago, we obtained the same result as your patient in a 34-year-old male Turkish
    patient with similar clinical data.

    1
    In conclusion, the two heterozygous HFE variants detected explain the iron accumulation. I got
    permission for the article from the Turkish patient. If your patient's approval and permission are
    obtained, the publication of the data that the c.340+4 T>C variant, which is registered as 'likely benign' in
    the database, creates iron accumulation when co-existing with p.His63Asp will be illuminating for cases
    where the same alleles are detected in the future.

    Sincerely

    Prof.Dr.Veysel Sabri Hançer


    Scientific Director
    Pentagene Genetics ShPK

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