A novel hemizygous CD40L mutation of X-linked hyper IgM syndromes and compound heterozygous DOCK8 mutations of Hyper IgE syndromes in two Chinese families

Abstract Background X-linked hyper IgM syndromes (X-HIGM) and autosomal recessive hyper IgE syndromes (HIES) are rare primary immunodeficiency diseases, characterized by recurrent infections due to the impairment in immune system. This study was aimed to investigate genotype-phenotype association and reveal the novel likely pathogenic mutations in CD40L and DOCK8 responsible to patients with X-HIGM and HIES respectively. Methods Whole exome sequencing (WES) and Sanger sequencing were performed to identify and verify the likely pathogenic mutations in the two families. Results A novel hemizygous mutation for CD40L in exon 2 (c.257delA) was identified in the first proband resulting in the substitution of glycine for glutamic acid at 86 codon of the protein causing the early termination of translation at downstream codon 9 (p.E86Gfs*9). Sanger sequencing verified that the variant was inherited from his mother. The second proband carried two novel compound heterozygous mutations in DOCK8, one at exon 14, c.1546C > G inherited from his father, another at exon 41, c.5355 + 6C > T(splicing) from his mother. Conclusion This study extends our knowledge to pathogenetic mutations spectrum of CD40L and DOCK8 which is helpful for accelerating prenatal diagnosis of X-HIGM and HIES and promoting timely treatment of patients.