Severe microcephaly

Gene: HMGB1

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 3 p.m. | Last Modified: 1 Feb 2023, 3 p.m.

Panel Version: 3.5

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update on ID and microcephaly gene panel based on >3 unrelated cases presenting with relevant phenotype due to heterozygous variant in the HMGB1 gene (PMID: 34164801)

Created: 1 Aug 2022, 10:59 a.m. | Last Modified: 1 Aug 2022, 10:59 a.m.

Panel Version: 3.1639

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

13q12.3 microdeletion syndrome is a rare cause of syndromic ID. Previous studies identified four genes within the ~300 Kb minimal critical region including two candidate protein coding genes: KATNAL1 and HMGB1.

Uguen et al. (2021) report 6 patients with LOF variants involving HMGB1 with features similar to 13q12.3 microdeletion syndrome (i.e. developmental delay, language delay, microcephaly, obesity and dysmorphic features). In silico analyses suggest that HMGB1 is likely to be intolerant to LOF, and previous in vitro data are in line with the role of HMGB1 in neurodevelopment. They suggest that haploinsufficiency of the HMGB1 gene may play a critical role in the pathogenesis of the 13q12.3 microdeletion syndrome.
Sources: Literature

Created: 9 Oct 2021, 7:53 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Developmental delay and microcephaly

Publications

• 34164801

Variants in this GENE are reported as part of current diagnostic practice