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Orphanet J Rare Dis. 2015 Jun 30;10:86. doi: 10.1186/s13023-015-0298-6.

Acquired familial Mediterranean fever associated with a somatic MEFV mutation in a patient with JAK2 associated post-polycythemia myelofibrosis.

Author information

1
Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. yshinar@sheba.health.gov.il.
2
Hematology Laboratory, Sheba Medical Center, Tel Hashomer, Israel. Tali.Tohami@gmail.com.
3
Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. alivenh@sheba.health.gov.il.
4
Department of Pathology, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Schiby.Ginette@sheba.health.gov.il.
5
Department of Oral Pathology & Oral Medicine, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel. Abraham.Hirshberg@sheba.health.gov.il.
6
Hematology Laboratory, Sheba Medical Center, Tel Hashomer, Israel. Meital.Nagar@sheba.health.gov.il.
7
Cancer Research Center, Sheba Medical Center, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Itamar.Goldstein@sheba.health.gov.il.
8
Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Rinat.Cohen@sheba.heath.gov.il.
9
Institute of Nephrology and Hypertension, Sheba Medical Center, Tel Hashomer, Israel. Olga.Kukuy@sheba.health.gov.il.
10
Maccabi Healthcare Organization, Petach Tikva, Israel. Ora.Shubman@sheba.health.gov.il.
11
Internal Medicine D, Sheba Medical Center and Sackler Faculty of Medicine, Tel Aviv, Israel. Yehonatan.Sharabi@sheba.health.gov.il.
12
Department of Immunology, Hospital Clinic-IDIBAPS, Barcelona, Spain. EVGONZAL@clinic.ub.es.
13
Department of Immunology, Hospital Clinic-IDIBAPS, Barcelona, Spain. JIAROSTE@clinic.ub.es.
14
Cancer Research Center, Sheba Medical Center, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Gidi.Rechavi@sheba.health.gov.il.
15
Hematology Laboratory, Sheba Medical Center, Tel Hashomer, Israel. Ninnette.Amariglio@sheba.health.gov.il.
16
Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Ophira.Salomon@sheba.health.gov.il.

Abstract

BACKGROUND:

A study was designed to identify the source of fever in a patient with post-polycythemia myelofibrosis, associated with clonal Janus Kinase 2 (JAK2) mutation involving duplication of exon 12. The patient presented with 1-2 day long self-limited periodic episodes of high fever that became more frequent as the hematologic disease progressed.

METHODS:

After ruling out other causes for recurrent fever, analysis of the pyrin encoding Mediterranean fever gene (MEFV) was carried out by Sanger sequencing in peripheral blood DNA samples obtained 4 years apart, in buccal cells, laser dissected kidney tubular cells, and FACS-sorted CD3-positive or depleted mononucleated blood cells. Hematopoeitc cells results were validated by targeted deep sequencing. A Sanger sequence based screen for pathogenic variants of the autoinflammatory genes NLRP3, TNFRSF1A and MVK was also performed.

RESULTS:

A rare, c.1955G>A, p.Arg652His MEFV gene variant was identified at negligible levels in an early peripheral blood DNA sample, but affected 46 % of the MEFV alleles and was restricted to JAK2-positive, polymorphonuclear and CD3-depleted mononunuclear DNA samples obtained 4 years later, when the patient experienced fever bouts. The patient was also heterozygous for the germ line, non-pathogenic NLRP3 gene variant, p.Q705K. Upon the administration of colchicine, the gold standard treatment for familial Mediterranean fever (FMF), the fever attacks subsided.

CONCLUSIONS:

This is the first report of non-transmitted, acquired FMF, associated with a JAK2 driven clonal expansion of a somatic MEFV exon 10 mutation. The non-pathogenic germ line NLRP3 p.Q705K mutation possibly played a modifier role on the disease phenotype.

PMID:
26123310
PMCID:
PMC4506767
DOI:
10.1186/s13023-015-0298-6
[Indexed for MEDLINE]
Free PMC Article

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