Novel pathogenic mutations identified in the first Chinese pedigree of complete C6 deficiency

Clinical & Translational Immunology
Philip H LiElaine Au

Abstract

Complete C6 deficiency (C6Q0) is a rare primary immunodeficiency leading to increased susceptibility to recurrent Neisseria infections. Patients with C6Q0 have mostly been reported in individuals of African ancestry previously, but never in Chinese. We identify the first Chinese patients with C6Q0 through family screening of an index case presenting with recurrent Neisseria meningitis with septicaemia and performed extensive clinical, serological and genetic investigations. Two variants in C6 were identified by next-generation sequencing and confirmed by Sanger sequencing in an index case of C6Q0. Immunological investigations, complement haemolytic assays (CH50/AH50), C6 gene sequencing and quantification of serum C6 levels were performed for all available members of his nonconsanguineous family. Three C6Q0 patients were identified with near-absent C6 levels, absent CH50/AH50 activity and compound heterozygous for two nonsense mutations in the C6 gene: NM_000065.4:c.1786C>T (p.Arg596Ter) and NM_000065.4:c.1816C>T (p.Arg606Ter). Neither mutations have been reported to be pathogenic previously. Two other family members who were heterozygous for either p.Arg596Ter or and p.Arg606Ter had intermediate C6 levels but preserved CH50/AH...Continue Reading

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Methods Mentioned

BETA
Genotyping
Exome Sequencing
ELISA
PCR

Software Mentioned

BaseSpace Onsite
GnomAD

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