Blood Res 2022; 57(S1):
Published online April 30, 2022
https://doi.org/10.5045/br.2022.2022056
© The Korean Society of Hematology
Correspondence to : Sun-Hee Kim, M.D., Ph.D.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
E-mail: sunnyhk@skku.edu
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Inherited bone marrow failure syndrome (IBMFS) is a group of clinically heterogeneous disorders characterized by significant hematological cytopenias of one or more hematopoietic cell lineages and is associated with an increased risk of cancer. The genetic etiology of IBMFS includes germline mutations impacting several key biological processes, such as DNA repair, telomere biology, and ribosome biogenesis, which may cause four major syndromes: Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. Although the clinical features of some patients may be typical of a particular IBMFS, overlapping and atypical clinical manifestations and variable penetrance pose diagnostic challenges. Here, we review the clinical and genetic features of the major forms of IBMFS and discuss their molecular genetic diagnosis. Next-generation sequencing-based gene panel testing or whole exome sequencing will help elucidate the genetic causes and underlying mechanisms of this genetically heterogeneous group of diseases.
Keywords Inherited bone marrow failure syndrome, Fanconi anemia, Dyskeratosis congenital, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Somatic genetic rescue
Blood Res 2022; 57(S1): S86-S92
Published online April 30, 2022 https://doi.org/10.5045/br.2022.2022056
Copyright © The Korean Society of Hematology.
Hyun-Young Kim, Hee-Jin Kim, Sun-Hee Kim
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence to:Sun-Hee Kim, M.D., Ph.D.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
E-mail: sunnyhk@skku.edu
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Inherited bone marrow failure syndrome (IBMFS) is a group of clinically heterogeneous disorders characterized by significant hematological cytopenias of one or more hematopoietic cell lineages and is associated with an increased risk of cancer. The genetic etiology of IBMFS includes germline mutations impacting several key biological processes, such as DNA repair, telomere biology, and ribosome biogenesis, which may cause four major syndromes: Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. Although the clinical features of some patients may be typical of a particular IBMFS, overlapping and atypical clinical manifestations and variable penetrance pose diagnostic challenges. Here, we review the clinical and genetic features of the major forms of IBMFS and discuss their molecular genetic diagnosis. Next-generation sequencing-based gene panel testing or whole exome sequencing will help elucidate the genetic causes and underlying mechanisms of this genetically heterogeneous group of diseases.
Keywords: Inherited bone marrow failure syndrome, Fanconi anemia, Dyskeratosis congenital, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Somatic genetic rescue
Table 1 . Characteristics of major inherited bone marrow failure syndrome..
Categories | Involved genes (estimated proportiona)) | Clinical and laboratory characteristics |
---|---|---|
Fanconi anemia | AR: AD: XLR: | Short stature, upper limb (radial ray) abnormalities, skin pigmentation (caféau lait macules), renal malformations, microcephaly. May have features of VACTERL-H. Pancytopenia, macrocytosis, elevated HbF, increased chromosome breakage. |
Dyskeratosis congenital (DC) and related telomere biology disorders | XLR: AD: AR: AD and AR: | Classic triad of DC: nail dystrophy, oral leukoplakia, skin pigmentation. Pulmonary fibrosis, liver disease. Pancytopenia, macrocytosis, very short telomeres. |
Diamond-Blackfan anemia | AD: XLR: | Cleft lip or palate, thumb abnormalities, cardiac malformations, short stature. Anemia, macrocytosis, reticulocytopenia. |
Shwachman-Diamond syndrome | AR: AD: | Exocrine pancreatic insufficiency, skeletal abnormalities. Neutropenia, low serum isoamylase, low serum trypsinogen. |
a)Estimated proportion of patients are not described for genes that are rarely involved..
Abbreviations: AD, autosomal dominant; AR, autosomal recessive; VACTERL-H, vertebral anomalies, anal atresia, cardiac anomalies, tracheo-esophageal fistula, esophageal atresia, renal structural anomalies, upper limb anomalies, hydrocephalus; XLR, X-linked recessive..
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