Combined Immunodeficiency

Gene: BLM

Green List (high evidence)

Well-established gene-disease association; more than 10 unrelated individuals and multiple BLM deficient mouse models demonstrate BS phenotypes such as a high rate of sister-chromatid exchange, Immunoglobulin deficiency and development of a variety of cancers.

Individuals reported as homozygous and compound heterozygous for BLM variants, with missense, and small deletions/insertion/duplications identified, resulting in premature protein truncation due to induced stop codons.

PMID: 17407155 (2007). In survey of 135 affected individuals, 64 different mutations were identified in 125 individuals.
In 102/125 individuals, the mutations identified were recurrent (shared by two or more individuals). Ethnic affiliations of the individuals with recurrent variants indicate founder mutations (inherited from a common ancestor); high frequency in Eastern European Jewish (Ashkenazi) population.

Created: 20 Jul 2021, 12:23 a.m. | Last Modified: 20 Jul 2021, 12:23 a.m.

Panel Version: 0.208

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Bloom Syndrome MIM# 210900; Short stature, dysmorphic facies; sun-sensitive; immunoglobulin deficiency (IgA, IgG, IgM); erythema; marrow failure; leukaemia; lymphoma; chromosomal instability; predisposition to malignancies

Publications

• 17407155
• 9285778
• 7585968
• 8079989
• 12242442
• 11101838