title: Variable expressivity of the clinical and biochemical phenotype associated with the apolipoprotein E p.Leu149del mutation.
abstract: Splenomegaly with sea-blue histiocytes, thrombocytopenia and hypertriglyceridemia is a very rare association that has been described in only one report to date. The molecular defect in the two reported patients consists in a deletion of a leucine at position 149 in the receptor-binding region of the apoE molecule. Here, we report on another family in whom the proband and his brother were diagnosed with splenomegaly, thrombocytopenia and hypertriglyceridemia. An apoE p.Leu149del mutation was found in both subjects. A large beta band in the VLDL fraction and elevated VLDL cholesterol-to-plasma triglyceride ratio was observed in the proband only. Their mother, presenting with isolated hypertriglyceridemia, also carried the same p.Leu149del mutation. The coexistence of factors facilitating the development of hypertriglyceridemia and/or low HDL-cholesterol level could explain why the proband and his brother developed a splenomegaly with thrombocytopenia, whereas the mother did not. Moreover, the presence of an apoE2 allele in the proband likely explains the more severe phenotype we observed in this subject. In conclusion, the apoE p.Leu149del mutation results in a very striking phenotype including one or all symptoms among splenomegaly, thrombocytopenia and hypertriglyceridemia, and should be considered as a differential diagnosis of storage disorders in the causes of splenomegaly with sea-blue histiocytes.
authors.affiliation: Centre de Génétique Médicale, Hôpital d'Enfants, Dijon, France. laurence.faivre@chu-dijon.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Pascale
authors.initials: P
authors.lastname: Saugier-Veber
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Pais de Barros
authors.forename: Bruno
authors.initials: B
authors.lastname: Verges
authors.forename: Bertrand
authors.initials: B
authors.lastname: Couret
authors.forename: Bernard
authors.initials: B
authors.lastname: Lorcerie
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin
authors.forename: Françoise
authors.initials: F
authors.lastname: Charbonnier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Philippe
authors.initials: P
authors.lastname: Gambert
authors.forename: Thierry
authors.initials: T
authors.lastname: Frebourg
authors.forename: Laurence
authors.initials: L
authors.lastname: Duvillard
mesh_terms: D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000235:genetics; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012618:Sea-Blue Histiocyte Syndrome / Q000235:genetics*; D013163:Splenomegaly / Q000235:genetics; D013577:Syndrome; D013921:Thrombocytopenia / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; D008074:Lipoproteins