P7
Case# P7, 2yo report
CasePresentingHPOs HP:0005528, HP:0001873
CasePreviousTesting genes related to MDS/inherited bone marrow failure syndromes was performed in patients, negative for this patient
CaseMethod1 NGS
CaseMethod2 Sanger
CaseGenotypingMethod NGS then variant confirmed with Sanger
Variant NM_152703.4(SAMD9L):c.2640C>A (p.His880Gln)
ClinVar 242372
CaseAddInfo transient monosomy 7 with somatic mutation of new variant NM_152703.3:c.3951_3955del (p.Ser1317ArgfsTer21) - CA658820702
P5
Case# P5, 7yo report
CasePresentingHPOs HP:0005528, HP:0001873
CasePreviousTesting genes related to MDS/inherited bone marrow failure syndromes was performed in patients, negative for this patient
CaseMethod1 NGS
CaseMethod2 Sanger
CaseGenotypingMethod NGS then variant confirmed with Sanger
Variant NM_152703.4(SAMD9L):c.2956C>T (p.Arg986Cys)
ClinVar 446530
VariantEvidence (Figure 5) 293FT cells transfected with p.Arg986Cys showed more limited cell proliferation than WT SAMD9L in 28202457
CaseAddInfo "The HLA-identical brother of P5 was thoroughly evaluated as a potential bone marrow donor. He was clinically healthy and had a normal complete blood count, but he did not qualify as a donor because of hypocellular bone marrow with mild dysplastic features. He was also a carrier of the p.R986C mutation."
P7
Case# P7, 2yo report
CasePresentingHPOs HP:0005528, HP:0001873
CasePreviousTesting genes related to MDS/inherited bone marrow failure syndromes was performed in patients, negative for this patient
CaseMethod1 NGS
CaseMethod2 Sanger
CaseGenotypingMethod NGS then variant confirmed with Sanger
Variant NM_152703.4(SAMD9L):c.2640C>A (p.His880Gln)
ClinVar 242372
CaseAddInfo transient monosomy 7 with somatic mutation of new variant NM_152703.3:c.3951_3955del (p.Ser1317ArgfsTer21) - CA658820702
P5
Case# P5, 7yo report
CasePresentingHPOs HP:0005528, HP:0001873
CasePreviousTesting genes related to MDS/inherited bone marrow failure syndromes was performed in patients, negative for this patient
CaseMethod1 NGS
CaseMethod2 Sanger
CaseGenotypingMethod NGS then variant confirmed with Sanger
Variant NM_152703.4(SAMD9L):c.2956C>T (p.Arg986Cys)
ClinVar 446530
VariantEvidence (Figure 5) 293FT cells transfected with p.Arg986Cys showed more limited cell proliferation than WT SAMD9L in 28202457
CaseAddInfo "The HLA-identical brother of P5 was thoroughly evaluated as a potential bone marrow donor. He was clinically healthy and had a normal complete blood count, but he did not qualify as a donor because of hypocellular bone marrow with mild dysplastic features. He was also a carrier of the p.R986C mutation."
F2: II-4
Case# Fam2:II-4, M, 7yo onset, Finnish
CasePresentingHPOs HP:0001310, HP:0001260, HP:0001251, HP:0000639, HP:0009072, HP:0008969, HP:0003487
CaseMethod1 WES
Variant NM_152703.4(SAMD9L):c.2672T>C (p.Ile891Thr)
ClinVar 446529
CaseAddInfo previously in 28202457
Table
Case# UW-AP:III-3, 60yo reported
CasePresentingHPOs HP:0001251, HP:0001310, HP:0001260, HP:0000639, HP:0007256
Variant NM_152703.4(SAMD9L):c.2640C>A (p.His880Gln)
ClinVar 242372
CaseAddInfo only genotyping methods described are for extended Family 1 or in a previous study. Is this UW family also from another study?
F2: II-4
Case# Fam2:II-4, M, 7yo onset, Finnish
CasePresentingHPOs HP:0001310, HP:0001260, HP:0001251, HP:0000639, HP:0009072, HP:0008969, HP:0003487
CaseMethod1 WES
Variant NM_152703.4(SAMD9L):c.2672T>C (p.Ile891Thr)
ClinVar 446529
CaseAddInfo previously in 28202457
Table
Case# UW-AP:III-3, 60yo reported
CasePresentingHPOs HP:0001251, HP:0001310, HP:0001260, HP:0000639, HP:0007256
Variant NM_152703.4(SAMD9L):c.2640C>A (p.His880Gln)
ClinVar 242372
CaseAddInfo only genotyping methods described are for extended Family 1 or in a previous study. Is this UW family also from another study?
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.
Family#PresentingHPOs HP:0000639
FamilyNotHPOs HP:0001251, HP:0001876, HP:0005528
CountryOrigin France
Family#Method1 WES
Family#Method2 Sanger
FamilyGenotypingMethod WES results confirmed with Sanger
Affected 3
Unaffected 2
Segregations 3
AddSegregationInfo family not to score
ProbandLabel UB612, M, 13mo diagnosis
CasePresentingHPOs HP:0005528, HP:0000639, HP:0001876
CaseAddInfo "Transplantation was planned but eventually cancelled because his blood cell counts improved spontaneously," possibly due to UPD.
Variant NM_152703.4(SAMD9L):c.2956C>T (p.Arg986Cys)
ClinVar 446530
VariantEvidence (Figure 5) 293FT cells transfected with p.Arg986Cys showed more limited cell proliferation than WT SAMD9L in 28202457
FamilyAddInfo Monosomy 7 in IV:1, mother and aunt also recovered, likely due to UPD or revertant mosaicism
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.
Family#PresentingHPOs HP:0000639
FamilyNotHPOs HP:0001251, HP:0001876, HP:0005528
CountryOrigin France
Family#Method1 WES
Family#Method2 Sanger
FamilyGenotypingMethod WES results confirmed with Sanger
Affected 3
Unaffected 2
Segregations 3
AddSegregationInfo family not to score
ProbandLabel UB612, M, 13mo diagnosis
CasePresentingHPOs HP:0005528, HP:0000639, HP:0001876
CaseAddInfo "Transplantation was planned but eventually cancelled because his blood cell counts improved spontaneously," possibly due to UPD.
Variant NM_152703.4(SAMD9L):c.2956C>T (p.Arg986Cys)
ClinVar 446530
VariantEvidence (Figure 5) 293FT cells transfected with p.Arg986Cys showed more limited cell proliferation than WT SAMD9L in 28202457
FamilyAddInfo Monosomy 7 in IV:1, mother and aunt also recovered, likely due to UPD or revertant mosaicism