Figure 5.
Figure 5. Characteristics in patients with SAMD9L and SAMD9 mutations. (A) G-banding ideogram of human chromosome 7 with genomic location of the tandem SAMD9 and SAMD9L genes. (B-C) Graphical representation of SAMD9L and SAMD9 proteins, respectively. Amino acid changes are indicated; see additional details in supplemental Figures 6 and 7. (D) Schematic of hematological history from birth to latest follow-up in the 16 patients with SAMD9 or SAMD9L mutations; see family trees in supplemental Figures 6 and 7, clinical characteristics in Table 4 and somatic evolution in supplemental Table 12. Median age of the SAMD9L and SAMD9 mutated patients at diagnosis was 13 months and 7 years, respectively (range, 8 months to 46 years, and 2 to 21 years, respectively). (E) Telomere length in PBMCs in 8 SAMD9L and 3 SAMD9 mutated patients, measured by flow cytometry fluorescence in situ hybridization. The vertical axis shows the relative telomere length determined in comparison with a control tetraploid cell line per percentage, whereas the horizontal axis displays age. Only 2 patients had short telomeres, and they also had a TERC and a RTEL1 mutation, respectively. (F) Family tree for patients UB609 and UB612 (arrows). The germ line SAMD9L mutation status is shown for the family members; +/−, heterozygous c.C2956T; +/+, no mutation. Patient UB612 (IV-1) was diagnosed with severe BMF and monosomy 7 without BM dysplasia at the age of 13 months. Transplantation was planned but eventually cancelled because his blood cell counts improved spontaneously. This patient is now 5 years old, without residual cytopenia or monosomy 7. His mother, patient UB609 (III-2), experienced a rather similar story 32 years previously; when she was 13 months old she was diagnosed with severe AA and BM transplantation was planned, which was also cancelled due to spontaneous improvement. Although they were not included in our IBMF cohort, we managed to investigate more patients in this family. The mother’s sister (III-3) also had early transitory pancytopenia, and both sisters, now aged 33 and 37 years, are doing well. Interestingly, the grandmother (II-2) had a cerebellar atrophy with ataxia, a nystagmus and the SAMD9L mutation found in her oral swab, whereas her own mother (I-2) also had the same neurological phenotype but could not be genetically explored. (G) Blood cell counts over time for patient UB612. The red curve indicates the hemoglobin concentration (Hb); light brown, the absolute neutrophil count (ANC); whereas the blue line indicates platelet counts (Pt). The gray area indicates the detection of monosomy 7 on marrow karyotyping.

Characteristics in patients with SAMD9L and SAMD9 mutations. (A) G-banding ideogram of human chromosome 7 with genomic location of the tandem SAMD9 and SAMD9L genes. (B-C) Graphical representation of SAMD9L and SAMD9 proteins, respectively. Amino acid changes are indicated; see additional details in supplemental Figures 6 and 7. (D) Schematic of hematological history from birth to latest follow-up in the 16 patients with SAMD9 or SAMD9L mutations; see family trees in supplemental Figures 6 and 7, clinical characteristics in Table 4 and somatic evolution in supplemental Table 12. Median age of the SAMD9L and SAMD9 mutated patients at diagnosis was 13 months and 7 years, respectively (range, 8 months to 46 years, and 2 to 21 years, respectively). (E) Telomere length in PBMCs in 8 SAMD9L and 3 SAMD9 mutated patients, measured by flow cytometry fluorescence in situ hybridization. The vertical axis shows the relative telomere length determined in comparison with a control tetraploid cell line per percentage, whereas the horizontal axis displays age. Only 2 patients had short telomeres, and they also had a TERC and a RTEL1 mutation, respectively. (F) Family tree for patients UB609 and UB612 (arrows). The germ line SAMD9L mutation status is shown for the family members; +/−, heterozygous c.C2956T; +/+, no mutation. Patient UB612 (IV-1) was diagnosed with severe BMF and monosomy 7 without BM dysplasia at the age of 13 months. Transplantation was planned but eventually cancelled because his blood cell counts improved spontaneously. This patient is now 5 years old, without residual cytopenia or monosomy 7. His mother, patient UB609 (III-2), experienced a rather similar story 32 years previously; when she was 13 months old she was diagnosed with severe AA and BM transplantation was planned, which was also cancelled due to spontaneous improvement. Although they were not included in our IBMF cohort, we managed to investigate more patients in this family. The mother’s sister (III-3) also had early transitory pancytopenia, and both sisters, now aged 33 and 37 years, are doing well. Interestingly, the grandmother (II-2) had a cerebellar atrophy with ataxia, a nystagmus and the SAMD9L mutation found in her oral swab, whereas her own mother (I-2) also had the same neurological phenotype but could not be genetically explored. (G) Blood cell counts over time for patient UB612. The red curve indicates the hemoglobin concentration (Hb); light brown, the absolute neutrophil count (ANC); whereas the blue line indicates platelet counts (Pt). The gray area indicates the detection of monosomy 7 on marrow karyotyping.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal