FAMILIAL SAMD9L MUTATION WWTH VARIABLE CLINICAL PHENOTYPE OF MDS/AML MONOSOMY 7 AND APLASTIC ANEMIA: A CASE OF TWO AFFECTED SIBLINGS..

Abstract

Introduction

SAMD9L mutation has been associated with hematological malignancies. The mutation has diverse hematological phenotypes ranging from Myelodysplastic syndrome (MDS) to Acute myeloid leukemia (AML)involving chromosome 7 aberration and recently described the emerging phenotype of aplastic anemia. We report two siblings with SAMD9L germline mutation born to asymptomatic consanguineous parents. each with different hematological phenotype.

Methods

Case #1: A 7- year old girl presented with thrombocytopenia & 4% peripheral blasts. She has no dysmorphic features . Family history is negative for hematological malignancies or BMF. She was diagnosed with MDS- Monomsomy7 . She transformed to AML over few weeks During this period her sibling presented with aplastic anemia, his (WES) revealed germline SAMD9L mutation which was detected in his sister . During chemotherapy of AED; there was interrupted due to septic shock so She was bridged with (Azacitadine + Venetoclax) prior to haploidentical BMT Case#2: A10- week old male presented with respiratory symptoms. He was diagnosed with Aplastic anemia and CMV pneumonitis .He was not dysmorphic WES revealed germline SAMD9L Mutation. although normal immunology workup, Natural Killer cell dysfunction was suspected based on SAMD9L mutation detection, early age of presentation, & resistant CMV-Viremia. He was treated for CMV infection and decided for haploidentical BMT

Results

We suggest to include SAMD9/SAMD9L in the standard AMLMDS genetic panel if additional system involved like immunodeficiency, neurological or genitourinary anomaly.

Conclusions

the heterogeneity of SAMD9L mutation even in family. High index of suspicious of this germline mutation is warranted in children with MDS.