A novel germline <i>SAMD9L</i> mutation in a family with ataxia-pancytopenia syndrome and pediatric acute lymphoblastic leukemia

Cheah, Jesse; Brown, Anna L.; Schreiber, Andreas W.; Jiang, Feng; Babic, Milena; Moore, Sarah; Young, Chun-Chun; Fine, Miriam; Phillips, Kerry; Guandalini, Michael; Wilson, Peter; Poplawski, Nicola; Hahn, Christopher N.; Scott, Hamish S.

doi:10.3324/haematol.2018.207316

Cited by 15 publications

(22 citation statements)

References 15 publications

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“…Severe cerebellar ataxia is observed in some but not all cases [ 117 ]. Some patients might show cerebellar atrophy, dysmetria, nystagmus, white matter abnormalities, and loss of Purkinje cells [ 117 , 140 , 141 ].…”

Section: Samd9 and Samd9l Syndromesmentioning

confidence: 99%

“…Mostly in patients with MIRAGE phenotype ( SAMD9 ) but also in several SAMD9L -mutated patients, severe invasive infections have been described. The causative organisms were bacteria (pseudomonas aeruginosa, clostridium difficile, staphylococcus, serratia marcescens, enterococcus faecium, escherichia coli, klebsiella pneumoniae, stenotrophomonas maltophilia, streptococcus pyogenes), viruses (MRSA, CMV, EBV, rhinovirus, coronavirus, varicella), and fungi (aspergillus, candida) causing sepsis, meningitis, otitis, sinusitis, laryngitis, hepatitis, bronchiolitis, pneumonia, neonatal necrotizing enterocolitis, pancolitis, gastroenteritis, enteropathy, urinary tract infections, otitis media, ecthyma gangrenosum, warts, dental abscesses, and urethritis [ 118 , 119 , 121 , 124 , 125 , [128] , [129] , [130] , [131] , [132] , [133] , [136] , [137] , [138] , [139] , 141 , [143] , [144] , [145] ]. However, the majority of non-syndromic SAMD9/9L -MDS patients generally do not appear to have increased risk to develop immune dysfunction and severe infections.…”

Section: Samd9 and Samd9l Syndromesmentioning

confidence: 99%

“…Thus far 38 distinct SAMD9 and 26 SAMD9L mutations have been identified in 110 symptomatic patients as mutually exclusive events [ 118 , 119 , 121 , 122 , 124 , 126 , [129] , [130] , [131] , [132] , [133] , [134] , [140] , [141] , [142] , [143] , 145 , 146 ]. The majority of these patients exhibit haematological phenotype with cytopenias, and/or MDS with monosomy 7.…”

Section: Samd9 and Samd9l Syndromesmentioning

confidence: 99%

“…The unique aspect of SAMD9/9L disease mechanism is ‘adaptation by aneuploidy’ that is achieved by the non-random loss chromosome 7 (−7/del(7q)) which contains mutated SAMD9/9L gene copy ( Fig. 2 ) [ 118 , 119 , 121 , 122 , 124 , 125 , 127 , 129 , 134 , 135 , [141] , [142] , [143] , [144] , [145] ]. The decrease of mutant allele in haematopoiesis poses a diagnostic challenge, since germline SAMD9/9L mutations show decreased variant allele frequency (VAF), with VAF even below 5% (own observations), necessitating germline validation in non-haematopoietic specimens, i.e.…”

Section: Samd9 and Samd9l Syndromesmentioning

confidence: 99%

“…Several case reports documented complete disappearance of −7 clones, thus far seen exclusively in young children, a phenomenon previously referred to as transient monosomy 7 syndrome [ 121 , 122 , 124 , 127 , [141] , [142] , [143] ]. However, −7 is a high risk lesion with malignant propensity (i.e.…”

Section: Samd9 and Samd9l Syndromesmentioning

confidence: 99%

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Germline predisposition in myeloid neoplasms: Unique genetic and clinical features of GATA2 deficiency and SAMD9/SAMD9L syndromes

Sahoo

Kozyra

Wlodarski

2020

Best Practice & Research Clinical Haematology

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Increasing awareness about germline predisposition and the widespread application of unbiased whole exome sequencing contributed to the discovery of new clinical entities with high risk for the development of haematopoietic malignancies. The revised 2016 WHO classification introduced a novel category of “myeloid neoplasms with germline predisposition” with GATA2 , CEBPA , DDX41 , RUNX1 , ANKRD26 , and ETV6 genes expanding the spectrum of hereditary myeloid neoplasms (MN). Since then, more germline causes of MN were identified, including SAMD9 , SAMD9L , and ERCC6L2 . This review describes the genetic and clinical spectrum of predisposition to MN. The main focus lies in delineation of phenotypes, genetics and management of GATA2 deficiency and the novel SAMD9/SAMD9L-related disorders. Combined, GATA2 and SAMD9/SAMD9L (SAMD9/9L) syndromes are recognized as most frequent causes of primary pediatric myelodysplastic syndromes, particularly in setting of monosomy 7. To date, ∼550 cases with germline GATA2 mutations, and ∼130 patients with SAMD9/9L mutations had been reported in literature. GATA2 deficiency is a highly penetrant disorder with a progressive course that often rapidly necessitates bone marrow transplantation. In contrast, SAMD9/SAMD9L disorders show incomplete penetrance with various clinical outcomes ranging from spontaneous haematological remission observed in young children to malignant progression.

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Section: Samd9 and Samd9l Syndromesmentioning

confidence: 99%

Section: Samd9 and Samd9l Syndromesmentioning

confidence: 99%

Section: Samd9 and Samd9l Syndromesmentioning

confidence: 99%

Section: Samd9 and Samd9l Syndromesmentioning

confidence: 99%

Section: Samd9 and Samd9l Syndromesmentioning

confidence: 99%

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Germline predisposition in myeloid neoplasms: Unique genetic and clinical features of GATA2 deficiency and SAMD9/SAMD9L syndromes

Sahoo

Kozyra

Wlodarski

2020

Best Practice & Research Clinical Haematology

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New SAMD9L heterozygous mutation leading to myelodysplastic syndrome and acute myeloid leukemia: A case report and review of the literature

Monagel

2023

Cancer Reports

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Background SAMD9L mutation is linked to the development of myeloid neoplasm. The mutation has a wide range of clinical presentations involving neurological, immunological, and hematological manifestations. Until now, limited data regarding different variants of this genetic mutation existed. Here we present a 6‐year‐old girl who presented with acute myeloid leukemia/myelodysplastic changes and who carries a new germline variant mutation in the SAMD9L gene. Case Presentation A 6‐year‐old girl who presented initially as a case of immune thrombocytopenic purpura (ITP) was later diagnosed with acute myeloid leukemia and myelodysplastic changes. In addition, she was found to have a new germline variant mutation in the SAMD9L gene (other known pathogenic variants known to cause ataxia pancytopenia syndrome). She was treated with chemotherapy followed by haplo identical transplant from her unaffected father. She is alive 30 months post‐transplant and in complete remission with full donor chimerism. Her initial brain MRI showed mild prominence of the anterior (superior) vermis folia, suggesting mild atrophy. Ongoing surveillance for accompanied neurological manifestation is ongoing, although the patient is asymptomatic. Conclusion For SAMD‐9L‐related disorder, a careful approach must be taken when a patient presents with a suspicious clinical feature even without a well‐known genetic mutation giving the diverse presentation across affected members within the same family. In addition, other associated abnormalities should be monitored long‐term.

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The International Consensus Classification (ICC) of hematologic neoplasms with germline predisposition, pediatric myelodysplastic syndrome, and juvenile myelomonocytic leukemia

et al. 2022

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A novel germline SAMD9L mutation in a family with ataxia-pancytopenia syndrome and pediatric acute lymphoblastic leukemia

Cited by 15 publications

References 15 publications

Germline predisposition in myeloid neoplasms: Unique genetic and clinical features of GATA2 deficiency and SAMD9/SAMD9L syndromes

Germline predisposition in myeloid neoplasms: Unique genetic and clinical features of GATA2 deficiency and SAMD9/SAMD9L syndromes

New SAMD9L heterozygous mutation leading to myelodysplastic syndrome and acute myeloid leukemia: A case report and review of the literature

The International Consensus Classification (ICC) of hematologic neoplasms with germline predisposition, pediatric myelodysplastic syndrome, and juvenile myelomonocytic leukemia

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