Page 92 - Haematologica Vol. 107 - September 2022

ARTICLE - Inherited cytopenias in children
O. Gilad et al.
ried variants in known relevant genes. Similarly, of 43 pa- tients with germline variants in SAMD9/L enrolled in the European Working Group of MDS in childhood (EWOG- MDS), 39 (91%) had RCC and only four (9%) had MDS-EB.40 The reason for this observation is currently unclear.
We observed phenotypic variability among the three pa- tients with biallelic variants in ERCC6L2: one is a 7-year- old boy who presented with IBMFS and two patients, aged 16 and 20 years, presented with MDS. The ERCC6L2 gene encodes for a transcription–coupled nucleotide excision
repair protein and when mutated, causes genomic insta- bility and affects mitochondrial function, leading to in- creased levels of reactive oxygen species.31 Most patients described so far were children presenting with IBMFS.41 Bluteau et al. found ERCC6L2 variants in seven (8%) of 86 patients diagnosed with IBMFS. However, two of these seven patients, both aged 22 years, had marrow dysplastic changes; and one patient developed AML at the age of 43 years.6 Poor prognosis AML-M6 was recently identified in adult members (aged 39-59 years) of four Finnish families,
Table 5. Clinical characteristics of patients referred with isolated thrombocytopenia.
Patient
Ethnic
origin/ Consangui- nity (+/-)
Gene
Disease/ Inheritance
MHGVS Coding
Age at diagnosis/ presentation
Hematological presentation
BM, cytogenetics and functional tests
Extra hematological manifestations
Outcome
4674
Jewish (-)
MYH9
IT/AD
NM_002473.6: c.287C>T -Ht
8-28d/18y
Thrombocytopenia
Mild myeloid hy- poplasia
Mental retardation, renal failure
Followup
4814
Jewish (-)
MYH9
IT/AD
NM_002473.5: c.4270G>A -Ht
1-7d/0.3y
Thrombocytopenia
Not done
None
Followup
5016
Arab Muslim (-)
MYH9
IT/AD
NM_002473.4: c.5797C>T -Ht
1-7d/5y
Thrombocytopenia
Reduced megakaryocytes
None
Followup
3870
Jewish (-)
MYH9
IT/AD
NM_002473.6: c.287C>T-Ht
1y/5y
Thrombocytopenia ("ITP")
Reduced megakaryocytes
None
Followup
5688
Jewish (-)
MYH9
IT/AD
NM_002473.5: c.4641G>T-Ht
0.9y/15y
Thrombocytopenia
Normal
None
Followup
5437
Jewish (-)
ACTN1
IT/AD
NM_001130004.1: c.1019C>T -Ht
1-7d/10.5y
Thrombocytopenia
Not done
None
Followup
4774
Jewish (-)
ACTN1
IT/AD
NM_001130004.1: c.1019C>T-Ht
8-28d/17y
Thrombocytopenia
Not done
None
Followup
5487
Arab Muslim (-)
CYCS
IT/AD
NM_018947.5: c.274A>G-Ht
0.5y/5y
Thrombocytopenia ("ITP")
Not done
None
Followup
4440
Arab Muslim (+)
NBEAL 2
IT/AR
NM_015175.3: c.7225-1G>C-Hm
8-28d/4y
Thrombocytopenia
Reduced megakaryocytes
None
Followup
5566
Jewish (-)
ANKRD 26
IT-MDS/AD
NM_001256053: c.-134G>A -Ht
8-28d/4y
Thrombocytopenia ("ITP")
Not done
None
Followup
3867
Jewish (-)
ANKRD 26
IT-MDS/AD
NM_014915.2: c.-127A>G –Ht
8-28d/20y
Thrombocytopenia
Not done
None
Followup
3610
Jewish (-)
ANKRD 26
IT-MDS/AD
NM_014915.3: c.-128G>T-Ht
8-28d/1.5y
Thrombocytopenia ("ITP")
Normal
None
Followup
5433
Jewish (-)
ANKRD 26
IT-MDS/AD
NM_001256053: c.-134G>A -Ht
1-7d/1y
Thrombocytopenia
Not done
None
Followup
5275
Jewish (-)
ETV6
IT-MDS/AD
NM_001987.4: c.1103T>G -Ht
0.7d/18y
Thrombocytopenia (“ITP”)
Hypocellular mar- row
None
Followup
5419
Arab Muslim (-)
ETV6
IT-MDS/AD
NM_001987.4 c.1104C>G-Ht
5.5d/6y
Thrombocytopenia
Not done
Developmental delay, short stature
Followup
5214
Jewish (-)
RUNX1
IT-MDS/AD
NM_001001890.2: c.532+1_532+10del GTAAGTGCAT-Ht
8-28d/2.5y
Thrombocytopenia
Reduced megakaryocytes
None
Followup
5878
Arab Muslim (+)
GALE
IT-MDS/AR
NM_000403.3: c.151C>T –Hm
8-28d/1.5y
Thrombocytopenia
Not done
None
Followup
BM: bone marrow; IT: inherited thrombocytopenia; MDS: myelodysplastic syndrome; AR: autosomal recessive; AD: autosomal dominant; y: years; d: days; Ht: heterozygous; Hm: homozygous; ITP: immune thrombocytopenia.
Haematologica | 107 September 2022
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