Page 196 - Haematologica Vol. 110 - January 2025

LETTER TO THE EDITOR
(Table 1). None of the patients had been diagnosed with a hematologic malignancy at time of collection. The BLM PV spanned amino acid 25 to 1,243, with most variants clus- tered in the DEAH helicase and RecQ helicase C-terminal domains (Figure 1A). Visual inspection of BLM variants confirmed family structure (Figure 1B).
No significant difference in mean number of total reads was identified between BSyn and control trio samples (Online
Supplementary Figure S1C; t test, P=0.268). After mapping to exome targets, BSyn trio samples had a mean coverage of 113.1x compared to controls with 106.5x coverage (Online Supplementary Figure S1D; t test, P=0.018). This coverage consistency extended across all chromosomes (Online Supplementary Figure S1E).
Samples were categorized into four groups: BSyn proband samples (N=10) designated as “affected”, BLM variant carrier
Table 1. Bloom syndrome patient and BLM pathogenic variant carrier demographics.
Sample Status Sex Age range Trio BSyn HGVS nomencalture of BLM mutation Cancer history, ID in years grouping status (NM_000057.4) type (years pc)
B179 Proband F 5-9 BLOOM_179 Affected NM_000057.4:c.[3727_3728insA];[3727_3728insA] No
C185 Father M 35-39 - Carrier NM_000057.4:c.3727_3728insA No
C184 Mother F 30-34 - Carrier NM_000057.4:c.3727_3728insA No
B286 Proband F 1-4 BLOOM_286 Affected NM_000057.4:c.[1933C>T];[c.3261del] No
C285 Father M 30-34 - Carrier NM_000057.4:c.1933C>T No
C287 Mother F 25-29 - Carrier NM_000057.4:c.3261del No
B360 Proband M <1 BLOOM_360 Affected NM_000057.4:c.[2207_2212delinsTAGATTC]; Yes, 1x ALL (7) [2207_2212delinsTAGATTC]
C353 Father M 30-34 - Carrier NM_000057.4:c.2207_2212delinsTAGATTC No
C354 Mother F 20-24 - Carrier NM_000057.4:c.2207_2212delinsTAGATTC No
B364 Proband M 35-39 BLOOM_364 Affected NM_000057.4:c.[2506_2507del];[2506_2507del]
Yes, 3x cSCC (1), 1x ALL (4)
C556 Father M 65-69 - Carrier NM_000057.4:c.2506_2507del No
C557 Mother F 60-64 - Carrier NM_000057.4:c.2506_2507del No
B380 Patient M 1-4 BLOOM_380 Affected
NM_000057.4:c.[2207_2212delinsTAGATTC]; Yes, 1x GIST (17), [2207_2212delinsTAGATTC] 1x DLBCL (20)
C381 Mother F 30-34 - Carrier NM_000057.4:c.2207_2212delinsTAGATTC No
B409 Proband M 1-4 BLOOM_409 Affected NM_000057.4:c.[2207_2212delinsTAGATTC]; Yes, AML (20) [2207_2212delinsTAGATTC]
C396 Father M 25-29 - Carrier NM_000057.4:c.2207_2212delinsTAGATTC No
C397 Mother F 20-24 - Carrier NM_000057.4:c.2207_2212delinsTAGATTC No
B488 Proband F 1-4 BLOOM_488 Affected NM_000057.4:c.[275del];[275del] No
C489 Father M 25-29 - Carrier NM_000057.4:c.275del No
C490 Mother F 30-34 - Carrier NM_000057.4:c.275del No
B498 Proband M 5-9 BLOOM_498 Affected NM_000057.4:c.[2695C>T];[2695C>T] No
C499 Father M 30-34 - Carrier NM_000057.4:c.2695C>T No
C500 Mother F 35-39 - Carrier NM_000057.4:c.2695C>T No
B502 Proband F 25-29 BLOOM_502 Affected NM_000057.4:c.[1933C>T];[1933C>T] Yes, BLCA (6)
C503 Father M 45-49 - Carrier NM_000057.4:c.1933C>T No
C504 Mother F 45-49 - Carrier NM_000057.4:c.1933C>T No
B615 Proband F 1-4 BLOOM_615 Affected NM_000057.4:c.[2695C>T];[3171_3172insT] No
C613 Father M 25-29 - Carrier NM_000057.4:c.3171_3172insT No
C614 Mother F 20-24 - Carrier NM_000057.4:c.2695C>T No
Bloom Syndrome patient (B#, N=10) and BLM pathogenic variant carrier (C#, N=19) parents included in our studies are identified with their patient (Bsyn) ID. Individual sex, age range, family grouping, BLM pathogenic variant and history of cancer are also shown. pc: post collection; M: male; F: female; ALL: acute lymphoblastic leukemia; cSCC: cutaneous squamous cell carcinoma; GIST: gastrointestinal stromal tumor; DLBCL: diffuse large B-cell lymphoma; AML: acute myeloid leukemia; BLCA: bladder carcinoma (Bsyn) ; HGVS: Human Genome Variation So- ciety; ins: insertions; del: deletions.
Haematologica | 110 January 2025
188