Association of mutations in mannose binding protein gene with childhood infection in consecutive hospital series

• Published in: BMJ Vol. 314; no. 7089; pp. 1229 - 1232
• Main Authors: Summerfield, John A, Sumiya, Michiko, Levin, Michael, Turner, Malcolm W
• Format: Journal Article
• Language: English
• Published: London British Medical Journal Publishing Group 26.04.1997; British Medical Association; BMJ Publishing Group Ltd; BMJ Publishing Group LTD; BMJ Publishing Group
• Edition: International edition
• Subjects: Adolescent; Age Factors; Alleles; Biological and medical sciences; Carrier proteins; Carrier Proteins - genetics; Child; Child health services; Child, Preschool; Childhood; Children; Children & youth; Codons; Disease Susceptibility; Diseases; Female; Gene mutation; Gene mutations; General aspects; Genes; Genetic aspects; Genetic mutation; Genotypes; Health risk assessment; Heterozygote; Homozygote; Hospitalization; Humans; Infant; Infant, Newborn; Infection; Infection - genetics; Infection pathogenesis; Infections; Infectious diseases; Lectins; Male; Mannose; Mannose-Binding Lectins; Medical sciences; Mutation; Pediatric diseases; Pediatrics; Physiological aspects; Proteins; Risk Factors; Transport proteins; Human; Infection; Binding protein; Prevalence; Gene; Risk factor; Predisposition; Mannose; Hospital; Mutation; Molecular biology; Child
• ISSN: 0959-8138; 0959-8146; 1468-5833; 1756-1833
• DOI: 10.1136/bmj.314.7089.1229

Abstract Objective: To determine the extent to which mutations in the mannose binding protein gene predispose to childhood infection. Design: Clinical details and genotype of mannose binding protein determined in consecutive children attending a paediatric department. Setting: Inner city hospital paediatric service in London. Subjects: 617 children attending hospital between October 1993 and August 1995. Main outcome measure: Infection as the cause for attendance or admission in relation to mutations in the mannose binding protein gene. Results: The prevalence of mutations in the mannose binding protein gene in children with infection (146/345) was about twice that in children without infection (64/272) (P<0.0001). Increased susceptibility to infection was found in both heterozygotic and homozygotic children. 13 out of 17 children homozygotic for variant alleles presented with strikingly severe infections, including 6 with septicaemia. Conclusions: The findings suggest that mutations in the mannose binding protein gene are an important risk factor for infections in children. Screening for such mutations should be included in the investigation of severe or frequent infections. Key messages Mutations in the mannose binding protein gene, which cause a common opsonic defect, are strongly associated with children presenting to hospital with infection The mutations increase susceptibility to infection in children who are heterozygotic or homozygotic for the mutations Children homozygotic for mannose binding protein gene mutations usually present with severe infections Investigation of severe or frequent infections should include screening for mannose binding protein gene mutations