SLC25A38 congenital sideroblastic anemia: Phenotypes and genotypes of 31 individuals from 24 families, including 11 novel mutations, and a review of the literature

Matthew M Heeney; Simon Berhe; Dean R Campagna; Joseph H Oved; Peter Kurre; Peter J Shaw; Juliana Teo; Mayada A Shanap; Hoda M Hassab; Bertil E Glader; Sanjay Shah; Ayami Yoshimi; Afshin Ameri; Joseph H Antin; Jeanne Boudreaux; Michael Briones; Kathryn E Dickerson; Conrad V Fernandez; Roula Farah; Henrik Hasle; Sioban B Keel; Timothy S Olson; Jacquelyn M Powers; Melissa J Rose; Akiko Shimamura; Sylvia S Bottomley; Mark D Fleming

doi:10.1002/humu.24267

SLC25A38 congenital sideroblastic anemia: Phenotypes and genotypes of 31 individuals from 24 families, including 11 novel mutations, and a review of the literature

Hum Mutat. 2021 Nov;42(11):1367-1383. doi: 10.1002/humu.24267. Epub 2021 Aug 5.

Authors

Matthew M Heeney¹, Simon Berhe², Dean R Campagna², Joseph H Oved³, Peter Kurre⁴, Peter J Shaw⁵, Juliana Teo⁶, Mayada A Shanap⁷, Hoda M Hassab⁸, Bertil E Glader⁹, Sanjay Shah¹⁰, Ayami Yoshimi¹¹, Afshin Ameri¹², Joseph H Antin¹³, Jeanne Boudreaux¹⁴, Michael Briones¹⁴, Kathryn E Dickerson¹⁵, Conrad V Fernandez¹⁶, Roula Farah¹⁷, Henrik Hasle¹⁸, Sioban B Keel¹⁹, Timothy S Olson²⁰, Jacquelyn M Powers²¹, Melissa J Rose²², Akiko Shimamura¹, Sylvia S Bottomley²³, Mark D Fleming²

Affiliations

¹ Division of Hematology, Dana-Farber Boston Children's Cancer and Blood Disorders Center and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
² Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
³ Cellular Therapy and Transplant Section, Division of Oncology and Comprehensive Bone Marrow Failure Center, Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, Philadelphia, USA.
⁴ Pediatric Comprehensive Bone Marrow Failure Center, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁵ BMT Services, Children's Hospital at Westmead; Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
⁶ Department of Haematology, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
⁷ King Hussein Medical Center, Amman, Jordan.
⁸ Department of Paediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
⁹ Division of Hematology-Oncology, Lucille Packard Children's Hospital, Stanford, California, USA.
¹⁰ Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, Arizona, USA.
¹¹ Department of Paediatrics and Adolescent Medicine, Division of Paediatric Haematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
¹² Division of Pediatric Hematology/Oncology, Department of Pediatrics, Augusta University, Augusta, Georgia, USA.
¹³ Hematopoietic Stem Cell Transplantation Program, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts, USA.
¹⁴ Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA.
¹⁵ Department of Pediatrics, University of Texas Southwestern, Dallas, Texas, USA.
¹⁶ Division of Hematology-Oncology, IWH Center, Dalhousie University, Halifax, Nova Scotia, Canada.
¹⁷ Department of Pediatrics, Lebanese American University Medical Center, Beirut, Lebanon.
¹⁸ Department of Pediatrics, Aarhus University Hospital, Aarhus University, Aarhus, Denmark.
¹⁹ Division of Hematology, University of Washington and Seattle Cancer Care Alliance, Seattle, Washington, USA.
²⁰ Cellular Therapy and Transplant Section, Division of Oncology and Comprehensive Bone Marrow Failure Center, Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
²¹ Texas Children's Hospital and Department of Pediatrics, Section of Hematology/Oncology, Baylor College of Medicine, Houston, Texas, USA.
²² Division of Hematology & Oncology, Nationwide Children's Hospital, Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
²³ Hematology-Oncology Section, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma, USA.

Abstract

The congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited disorders of erythropoiesis characterized by pathologic deposits of iron in the mitochondria of developing erythroblasts. Mutations in the mitochondrial glycine carrier SLC25A38 cause the most common recessive form of CSA. Nonetheless, the disease is still rare, there being fewer than 70 reported families. Here we describe the clinical phenotype and genotypes of 31 individuals from 24 families, including 11 novel mutations. We also review the spectrum of reported mutations and genotypes associated with the disease, describe the unique localization of missense mutations in transmembrane domains and account for the presence of several alleles in different populations.

Keywords: erythropoiesis; genetics; hematopoietic stem cell transplantation; iron; sideroblastic anemia.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Anemia, Sideroblastic / congenital*
Child, Preschool
Female
Genotype*
Humans
Infant
Infant, Newborn
Male
Mitochondrial Membrane Transport Proteins / genetics*
Mutation*
Phenotype*

Substances

Mitochondrial Membrane Transport Proteins
Slc25a38 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding