Genetics of Sideroblastic Anemia Mohammad Keramatipour MD Ph

Genetics of Sideroblastic Anemia Mohammad Keramatipour MD, Ph. D Keramatipour@tums. ac. ir 1

Sideroblastic Anemia n Definition n Classification: Ø Inherited / Congenital Ø Acquired 2

Inherited Sideroblastic Anemias n Locus heterogeneity n Patterns of inheritance: Ø X-linked recessive û ALAS 2 & ABCB 7 genes Ø Autosomal recessive û SLC 25 A 38, GLRX 5, LARS 2, PUS 1, YARS 2, & TRNT 1 genes (SLC 19 A 2 ? ? ) Ø Autosomal dominant û HSPA 9 3

X-linked Sideroblastic Anemia n X-linked sideroblastic anemia Ø ALAS 2 gene: erythroid ALA-synthase, role in synthesis of aminolevulinic acid (ALA), a precursor of heme n X-linked sideroblastic anemia and ataxia Ø ABCB 7 gene: ABCB 7, ATP-binding cassette sub-family B member 7 protein 4

X-linked Sideroblastic Anemia n Features of X-linked recessive inheritance Ø Most affected are males Ø Mothers are carriers – some affected due to skewed X-inactivation Ø Affected males do not pass the disease 5

Autosomal Recessive SAs n Sideroblastic anemia, 2, pyridoxine refractory: SLC 25 A 38 n Sideroblastic anemia, 3, pyridoxine refractory: GLRX 5 n Hydrops, lactic acidosis, and sideroblastic anemia: LARS 2 n Myopathy, lactic acidosis, and sideroblastic anemia 1: PUS 1 n Myopathy, lactic acidosis, and sideroblastic anemia 2: YARS 2 n Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay: TRNT 1 6

Autosomal Recessive SAs 7

Autosomal Dominant SA n Sideroblastic anemia, 4: HSPA 9 8

Case Report n An 8 -month-old female was referred to us in Khordad 96 n Microcytic hypochromic anemia n First cousin parents n WES was performed using Agilent V 6 capturing system – Sequencing done by Illumina Hi. Seq 4000 machine 9

WES Result n Solute carrier family 25 member 38 (SLC 25 A 38) 10

Variant Interpretation 11

WES Result n Carrier for hearing loss 12

Thank you for listening, any comments? 13

Acknowledgments Patents and families, physicians, & our team members 14