Properdin deficiency associated with recurrent otitis media and pneumonia, and identification of male carrier with Klinefelter syndrome

TY - JOUR

T1 - Properdin deficiency associated with recurrent otitis media and pneumonia, and identification of male carrier with Klinefelter syndrome

AU - Schejbel, Lone

AU - Rosenfeldt, Vibeke

AU - Marquart, Hanne

AU - Valerius, Niels Henrik

AU - Garred, Peter

N1 - Keywords: Female; Genetic Predisposition to Disease; Heterozygote; Humans; Klinefelter Syndrome; Male; Mutation; Otitis Media; Pedigree; Pneumonia; Properdin; Questionnaires; Recurrence; Retrospective Studies

PY - 2009

Y1 - 2009

N2 - Properdin is an initiator and stabilizer of the alternative complement activation pathway (AP). Deficiency of properdin is a rare X-linked condition characterized by increased susceptibility to infection with Neisseria meningitidis associated with a high mortality rate. We report properdin deficiency in a large Pakistani family. The index cases were found by screening for immunodeficiency due to a history of recurrent infections. This revealed absent AP activity, but normal classical and lectin pathway activity. Sequencing of the properdin gene (PFC) revealed a novel frameshift mutation. When all available relatives (n=24) were screened for the mutation, four affected males, four female carriers and a male heterozygous carrier were identified. He was subsequently diagnosed with Klinefelter syndrome. A questionnaire revealed a striking association between properdin deficiency and recurrent otitis media (P=0.0012), as well as recurrent pneumonia (P=0.0017). This study is the first to show a significant association between properdin deficiency and recurrent infections.

AB - Properdin is an initiator and stabilizer of the alternative complement activation pathway (AP). Deficiency of properdin is a rare X-linked condition characterized by increased susceptibility to infection with Neisseria meningitidis associated with a high mortality rate. We report properdin deficiency in a large Pakistani family. The index cases were found by screening for immunodeficiency due to a history of recurrent infections. This revealed absent AP activity, but normal classical and lectin pathway activity. Sequencing of the properdin gene (PFC) revealed a novel frameshift mutation. When all available relatives (n=24) were screened for the mutation, four affected males, four female carriers and a male heterozygous carrier were identified. He was subsequently diagnosed with Klinefelter syndrome. A questionnaire revealed a striking association between properdin deficiency and recurrent otitis media (P=0.0012), as well as recurrent pneumonia (P=0.0017). This study is the first to show a significant association between properdin deficiency and recurrent infections.

U2 - 10.1016/j.clim.2009.02.008

DO - 10.1016/j.clim.2009.02.008

M3 - Journal article

C2 - 19328743

SN - 1521-6616

VL - 131

SP - 456

EP - 462

JO - Clinical Immunology

JF - Clinical Immunology

IS - 3

ER -