先天性红细胞生成异常性贫血 Ia 型伴新型 CDAN1 基因突变，经全外显子组测序诊断。
Congenital dyserythropoiesis anemia type Ia with a novel CDAN1 mutation diagnosed by whole exome sequencing.
机构信息
Division of Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
出版信息
Mol Genet Genomic Med. 2020 May;8(5):e1220. doi: 10.1002/mgg3.1220. Epub 2020 Mar 11.
BACKGROUND
Congenital dyserythropoiesis anemia type Ia (OMIM:224120), is a rare hereditary anemia. The diagnosis is difficult to make and usually delayed in part due to its rarity and nonspecific clinical manifestations.
METHODS
Whole exome sequencing was applied for the genetic diagnosis of a 12-year-old boy who has suffered from hemolytic anemia since birth and who requires regular transfusions. Sanger sequencing of the variants detected in whole exome sequencing was performed in the patient and his parents.
RESULTS
Compound heterozygous mutations of CDAN1 gene, including one previously reported and one novel mutation, which is a splicing change, were detected in the whole exome sequencing and confirmed by Sanger sequencing. The autosomal recessive inheritance was confirmed by pedigree analysis.
CONCLUSION
To our knowledge, this is the first case report of congenital dyserythropoiesis anemia type Ia with genetic diagnosis to be located in Taiwan. Because of the rarity of CDA Ia and the overlapping of the clinical manifestations with other hereditary anemias, the next-generation sequencing approach is effective for conclusive diagnosis of CDA Ia.
背景
先天性红细胞生成性卟啉病贫血Ⅰa 型（OMIM：224120）是一种罕见的遗传性贫血。由于其罕见性和非特异性临床表现，部分患者的诊断较为困难且常被延误。
方法
对一名 12 岁男孩进行了全外显子组测序，该男孩自出生以来即患有溶血性贫血，需要定期输血。对全外显子组测序中发现的变异进行了 Sanger 测序，并在患者及其父母中进行了检测。
结果
在全外显子组测序中检测到 CDAN1 基因的复合杂合突变，包括一个先前报道的突变和一个新的剪接突变，该突变通过 Sanger 测序得到了证实。通过家系分析证实了常染色体隐性遗传模式。
结论
据我们所知，这是首例在台湾地区进行基因诊断的先天性红细胞生成性卟啉病贫血Ⅰa 型病例报告。由于 CDA Ia 的罕见性以及与其他遗传性贫血的临床表现重叠，下一代测序方法对于 CDA Ia 的明确诊断是有效的。
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