Primary complement C5 deficiencies – Molecular characterization and clinical review of two families

TY - JOUR

T1 - Primary complement C5 deficiencies – Molecular characterization and clinical review of two families

AU - Schejbel, Lone

AU - Fadnes, Dag

AU - Permin, Henrik

AU - Lappegård, Knut Tore

AU - Garred, Peter

AU - Mollnes, Tom Eirik

PY - 2013/10

Y1 - 2013/10

N2 - Inherited deficiency states of the terminal complement component C5 are rare and often associated with increased risk of recurrent Neisseria infections. More than 50 cases with primary C5 deficiency have been reported. In spite of this, the molecular basis has only been documented in a few cases. In the present study we investigated two unrelated Caucasian probands with C5 deficiency originating from Norway and Denmark, respectively, and found three previously undescribed mutations. With these data, thirteen mutations associated with C5 deficiency have been described. By genetic screening of the family of the Norwegian patient, previously diagnosed as homozygous C5 deficient and suffering four Neisseria infections, an additional case of C5 deficiency was discovered, who had experienced one episode of Neisseria infections. Detailed review of the clinical history of the patients and their healthy relatives did not reveal any differences between C5 deficient and sufficient individuals with regard to clinical presentation, apart from the susceptibility to Neisseria infections. Of note, one of the patients described here, and several C5 deficient patients from the literature had Neisseria meningitidis serotype B infections, which is not covered by the current vaccines. These data support the clinical guidelines for patients treated with C5 inhibitors, who are functional C5 deficient by the treatment.

AB - Inherited deficiency states of the terminal complement component C5 are rare and often associated with increased risk of recurrent Neisseria infections. More than 50 cases with primary C5 deficiency have been reported. In spite of this, the molecular basis has only been documented in a few cases. In the present study we investigated two unrelated Caucasian probands with C5 deficiency originating from Norway and Denmark, respectively, and found three previously undescribed mutations. With these data, thirteen mutations associated with C5 deficiency have been described. By genetic screening of the family of the Norwegian patient, previously diagnosed as homozygous C5 deficient and suffering four Neisseria infections, an additional case of C5 deficiency was discovered, who had experienced one episode of Neisseria infections. Detailed review of the clinical history of the patients and their healthy relatives did not reveal any differences between C5 deficient and sufficient individuals with regard to clinical presentation, apart from the susceptibility to Neisseria infections. Of note, one of the patients described here, and several C5 deficient patients from the literature had Neisseria meningitidis serotype B infections, which is not covered by the current vaccines. These data support the clinical guidelines for patients treated with C5 inhibitors, who are functional C5 deficient by the treatment.

U2 - 10.1016/j.imbio.2013.04.021

DO - 10.1016/j.imbio.2013.04.021

M3 - Journal article

C2 - 23743184

SN - 0171-2985

VL - 218

SP - 1304

EP - 1310

JO - Immunobiology

JF - Immunobiology

IS - 10

ER -