Page 58 - Haematologica3

R. Bottega et al.
Table 1. Molecular and clinical data of Fanconi anemia individuals with biallelic or monoallelic p.His913Proand p.Arg951Gln alleles of FANCA.
Patient/ Status sex
F1/M Homozygous
F2/F* Homozygous
Mutation
c.2738A>C p.His913Pro
c.2738A>C p.His913Pro
c.2738A>C p.His913Pro
Present age (age at diagnosis)
11 (10)
Congenital malformations
Bilateral thumb hypoplasia, patency
of the ductusarteriosus Growth delay, strabismus,
Malformation score
11 Moderate
2 Mild
10 Moderate
9 Moderate
22 Severe
6 Moderate
2 Mild
1 Mild
1 Mild
7 Moderate
Hematologic features
Haematologic score
24
(6) astigmatism, microphthalmia,
Mild bi-lineage 3 cytopenia; Mild
no transfusion support
Cytopenia 7
tri-lineage before HSCT (17-year-old); no transfusion before HSCT
Moderate
F3/M
F4/F
F5/M
F6/M
F7/M
F8/M
F9/M
F10/M
F11/F*
Homozygous
Compound heterozygous
hypopigmentation (area), triangular face, micrognazia
26 Growth delay,
(16) strabismus, myopia, microphthalmia,
widespread hyperpigmentation, triangular face, visual impairment, hypospadias
13 Growth delay, (4) duodenal atresia,
hyperpigmentation (area), cafè au lait spots
18 Growth delay, (7) syndactyly,
Leukopenia before 5
c.2738A>C p.His913Pro c.3715_3729del p.Glu1239_Arg1243del
Leukopenia and 6
HSCT (18-year-old); HSCT no transfusion before
Moderate
thrombocytopenia before HSCT (9-year-old); no transfusion before HSCT
Moderate
Compound c.2738A>C heterozygous p.His913Pro
c.894-?_1470+?del
Compound c.2738A>C heterozygous p.His913Pro c.2852G>A
p.Arg951Glns Compound c.2852G>A heterozygous p.Arg951Gln
c.284-?_426+?del p.Gly95Glufs*38
Compound c.2852G>A heterozygous p.Arg951Gln
c.4261-19_4261-12del
Compound c.2852G>A
heterozygous p.Arg951Gln c.3558dup
p.Arg1187Glufs*28 c.2852C>T
p.Arg951Gln c.2T>A p.? c.2851C>T
Cytopenia 11
19 (15)
22 (11)
Dead at 9 (6)
Dead at 21 (10)
15 (6)
20 (7)
Triangular face
Growth delay
Growth delay, hyperpigmentation, triangular face, unilateral ectopic kidney
Microphthalmia, triangular face,
hyperpigmentation, hearing loss
Leukopenia at diagnosis; 2 at present, blood count Mild
in the normal range
Mild neutropenia 2 Mild
Thrombocytopenia 9
triangular face, unilateral (right) renal hypoplasia, micropenis, hypospadias Growth delay,
astigmatism, microphthalmia, widespread hyperpigmentation, triangular face, micrognazia Growth delay,
cutaneous hyperpigmentation
tri-lineage before HSCT (9-year-old); transfusion before HSCT
Severe
evolved in severe tri-lineage cytopenia concomitantly with MDS/AML. Dead after two HSTC for relapse (9-year-old)
Severe
Bi-lineage cytopenia. 7
Dead for CMV infection after HSCT (21-year-old)
Moderate
418
Compound heterozygous
Compound
Thrombocytopenia 8
heterozygous p.Arg951Trp c.1777-7_1779del
7 At diagnosis mild thrombocytopenia 7
Moderate evolved in tri-lineage Moderate left mild conductive
cytopenia before HSCT (17-year-old); transfusions before HSCT
evolved in tri-lineage cytopenia before HSCT (12-year-old); transfusions before HSCT
Moderate
*Potential hematologic mosaicism.In F2 lymphoblasts a de novo compensatory mutation c.2737C>G/p.His913Ala is likely to restore the allele function.In F11 lymphoblast cell lines the c.1777-7_1779del was not detected, suggesting that a back mutation event occurred in these cells. For all of these patients, it was not possible to establish when and to what extent the revertant event occurred.
haematologica | 2018; 103(3)