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

• Main Authors: Leonore Greybe (Author), Daniel Leung (Author), Nicole Wieselthaler (Author), David M le Roux (Author), Koon Wing Chan (Author), Yu Lung Lau (Author), Brian Eley (Author)
• Format: Book
• Published: BMC, 2023-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/s12887-023-04206-8; 1471-2431
• Keywords: BCG complications; BCG osteomyelitis; Disseminated BCG; STAT1 deficiency; STAT1 mutation; MSMD; Pediatrics; RJ1-570
• Source: BMC Pediatrics, Vol 23, Iss 1, Pp 1-6 (2023)

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.