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

BMC Pediatr. 2023 Jul 29;23(1):378. doi: 10.1186/s12887-023-04206-8.

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.

Keywords: BCG complications; BCG osteomyelitis; Disseminated BCG; MSMD; Pediatrics; STAT1 deficiency; STAT1 mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BCG Vaccine* / adverse effects
  • Child
  • Female
  • Humans
  • Male
  • Mothers*
  • Mutation
  • STAT1 Transcription Factor / genetics
  • South Africa

Substances

  • BCG Vaccine
  • STAT1 protein, human
  • STAT1 Transcription Factor