A rare mutation causing autosomal dominant STAT1 deficiency in a South African multiplex kindred with disseminated BCG infection

Greybe, Leonore; Leung, Daniel; Wieselthaler, Nicole; le Roux, David M.; Chan, Koon W.; Lau, Yu L.; Eley, Brian

A rare mutation causing autosomal dominant STAT1 deficiency in a South African multiplex kindred with disseminated BCG infection

Journal Article

2023-07-29

Journal Title

BMC Pediatrics

Link to Journal

https://bmcpediatr.biomedcentral.com/

License

http://creativecommons.org/licenses/by/4.0/

Abstract

Abstract Background Autosomal dominant signal transducer and activator of transcription 1 (STAT1) deficiency, part of the Mendelian susceptibility to mycobacterial disease (MSMD) group, frequently causes disseminated Bacillus Calmette-Guérin (BCG) infections, but has not been reported from Sub-Saharan Africa (SSA) where routine birth BCG vaccination is practiced. Case presentation Two half-siblings presented five years apart, with multifocal osteomyelitis as the dominant feature of disseminated BCG, which was successfully treated with antimycobacterial therapy. Whole exome sequencing demonstrated a novel heterozygous substitution in the splice site between intron 13 and exon 14 of the STAT1 gene, NM_007315: c.1128-1G>A, in the proband and his mother and was later confirmed in his half-brother. Conclusions Children with BCG vaccine complications in SSA should be referred for further investigation and particular consideration of MSMD.