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Familial thrombocytosis caused by the novel germ-line mutation p.Pro106Leu in the MPL gene

El-Harith Abdelghaffar El-Harith1, Cornelia Roesl, Matthias Ballmaier

  • 1Institute of Human Genetics, Medical University of Hannover, Hannover, Germany.

British Journal of Haematology
|November 28, 2008
PubMed

Insights

A novel MPL gene mutation, p.Pro106Leu, causes familial thrombocytosis (FT) in Arab families. Homozygotes exhibit severe thrombocytosis, while heterozygotes may show mild symptoms, suggesting an autosomal-recessive inheritance pattern.

Area of Science:

  • Genetics
  • Hematology
  • Molecular Biology

Background:

  • Familial thrombosis (FT) is a rare, typically autosomal-dominant disorder.
  • Mutations in the thrombopoietin gene (THPO) or myeloproliferative leukaemia virus oncogene (MPL) gene are known causes of FT.
  • The MPL gene encodes the thrombopoietin receptor.

Purpose of the Study:

  • To investigate the genetic basis of familial thrombocytosis in an Arab family.
  • To identify novel mutations associated with familial thrombocytosis.
  • To determine the inheritance pattern and prevalence of identified mutations.

Main Methods:

  • Linkage analysis was performed on an Arab family with severe thrombocytosis.
  • MPL gene sequencing was conducted to identify mutations.
  • Genotyping of controls and patients was performed to assess mutation frequency.

Main Results:

  • A novel MPL germline mutation, p.Pro106Leu (c.317C > T), was identified in homozygous form in siblings with severe thrombocytosis.
  • Homozygosity for p.Pro106Leu was found in six additional familial thrombocytosis patients from three Arab families.
  • Heterozygous carriers (18 individuals) showed normal platelet counts (14) or mild thrombocytosis (4).
  • The p.Pro106Leu mutation was absent in 193 healthy German controls but present in 3.3% of 213 unrelated Arabs (P < 0.001).

Conclusions:

  • The MPL mutation p.Pro106Leu is strongly associated with familial thrombocytosis.
  • p.Pro106Leu is a frequent MPL mutation in the Arab population.
  • The inheritance pattern appears autosomal-recessive with potential mild manifestation in heterozygotes, differing from typical autosomal-dominant FT.

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