Anemia, Dyserythropoietic, Congenital/complications* ; Cholelithiasis/complications* ; Hemochromatosis ; Humans

OBJECTIVE: To identify the pathogenic variants of 4 patients with hemolytic anemia of unknown cause. METHODS: Peripheral blood samples of the patients and their family members were collected to extract DNA. The coding region and splice region in all exons of gene of erythrocyte related diseases were analyzed by using target sequence capture and high-throughput sequencing technology. Suspected pathogenic variants were verified by PCR combined Sanger sequencing technology. RESULTS: Each of the probands was detected two compound heterozygous variants, and CDA II was diagnosed. Six variants were detected in the 4 probands, four variants were reported and the other two were first reported. CONCLUSION By high-throughput sequencing, gene variant of CDA II be analyzed fast and accurately. It is an effective supplement to convenional diagnostic methods. Furthermore, the novel variant sites have enriched the variant database of the SEC23B gene.
Anemia, Dyserythropoietic, Congenital/genetics* ; Exons/genetics* ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Vesicular Transport Proteins/genetics*

OBJECTIVE: To explore the clinical feature, diagnosis and phenotype of Majeed syndrome. METHODS: Clinical manifestation, diagnostic process, imaging feature and genetic testing of an ethnic Han Chinese patient with Majeed syndrome were reviewed. RESULTS: The patient, a 3-year-9-month-old boy, had featured psychomotor retardation and developed bone pain from 8 month on. The child had tenderness of the lower limbs and presented with repeatedly joint swelling and pain accompanied by fever. Physical signs included limb muscle weakening, slightly decreased muscle tone, reduced muscle volume and positive Gower sign. High-throughput sequencing revealed that the child has carried compound heterozygous variants of the LPIN2 gene, including c.1966A>G and c.2534delG. MRI showed multiple lesions in bilateral knee joints and distal middle tibia presenting as patchy SPAIR high signals with unclear edge, in addition with edema of soft tissue surrounding the right distal femur. CONCLUSION Majeed syndrome is characterized by chronic and recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and growth retardation. Surrounding muscle tissue of osteomyelitis may also be involved. The syndrome may also affect the central nervous system, resulting in delayed language and motor development. Discovery of multiple pathological variants of the LPIN2 gene suggested that the clinical phenotype of this syndrome may vary between patients to some extent.
Anemia, Dyserythropoietic, Congenital/genetics* ; Child ; Genetic Testing ; Humans ; Immunologic Deficiency Syndromes/genetics* ; Infant ; Male ; Osteomyelitis/genetics*

Objective: To enrich the gene mutation sites and accumulate treatment experience of congenital dyserythropoietic anemia (CDA) type Ⅱ by reporting one case of CDA patient with new mutation site of SEC23B and was successfully treated by homozygous allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The mutation within SEC23B gene in a child case with the reduced hemoglobin for more than 3 months, and his family were analyzed in combination with literatures review. Results: A 3-day 5-month female child was admitted due to "decreasing hemoglobin for more than 3 months" , blood routine test showed HGB 44 g/L, positive for acid hemolysis test (Ham test) . Bone marrow showed that the proportion of erythroid line was 69%, mainly middle and late juvenile erythrocytes, binuclear and odd nucleated erythrocytes could be observed, and nuclear fragmentation and nuclear budding could be seen occasionally in nucleated erythrocytes, transmission electron microscopy disclosed that bone marrow harbored the typical double-layer membrane structure of nuclear erythrocytes. There were two unreported new mutation sites in the SEC23B gene, including 1504 G>C/wt and c. 2254-2255 insert A/wt. The two mutations were derived from the father and mother of the child respectively. At the late stage, the child was successfully treated with allo-HSCT, the original mutation turned negative. Conclusion: This study reported the mutation type of SEC23B gene insertion for the first time in China. Allo-HSCT could be utilized as a treatment for CDA.
Anemia, Dyserythropoietic, Congenital/genetics* ; China ; Erythroblasts ; Female ; Humans ; Mutation ; Vesicular Transport Proteins/genetics*

OBJECTIVETo detect potential mutation in a family affected with congenital dyserythropoietic anemia type II (CDA II).

METHODSTargeted sequence capture and next-generation sequencing (NGS) were used to analyze the exons and exon-intron boundaries of the SEC23B gene in a clinically suspected CDA II patient. Genotypes of the relatives were validated by Sanger sequencing. Potential impact of amino acid substitution on the structure and function of SEC23B protein was predicted with MutationTaster and PolyPhen-2. The protein structure was predicted with SWISS-MODEL software.

RESULTSThe proband was found to harbor double heterozygous mutations of the SEC23B gene, c.1727T>C (p.F576S) and c.1831C>T (p.R611W), which resulted in amino acid substitutions p.F576S and p.R611W. Both mutations were confirmed by Sanger sequencing. The sister of the proband was found to have carried c.1727T>C (p.F576S), while her father and son have carried c.1831C>T (p.R611W) mutation. In addition, the proband was detected to have carried c.211C>T (p.R71X) of the HFE gene, which resulted in substitution of arginine by a stop codon. The impact of above mutations on the structure or function of protein was predicted to be harmful. Splenectomy and iron chelation therapy have achieved effective improvement of anemia and iron overload. Computer simulation suggested that the mutations have altered the 3D structure of the SEC23B protein.

CONCLUSIONThe novel compound mutations of c.1727T>C and c.1831C>T of the SEC23B gene probably underlie the CDA II in the family, and there is a strong correlation between the genotype and phenotype.

Adult ; Anemia, Dyserythropoietic, Congenital ; genetics ; Computer Simulation ; Family ; Female ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Phenotype ; Vesicular Transport Proteins ; genetics

It has been known that extramedullary hematopoiesis occurring after birth can be developed in various diseases, and it is often found in hematologic diseases. Among these, congenital dyserythropoietic anemia is a rare disease characterized with increase of ineffective hematopoiesis and morphological abnormalities of erythroblasts. In congenital dyserythropoietic anemia, extramedullary hematopoiesis is very rare and only a few cases have been reported. Although treatment is not required if there is no symptom in extramedullary hematopoiesis, surgery or radiation therapy is effective in case that there is symptom or unresponsive anemia despite blood transfusion. This case report is about surgical treatment for extramedullary hematopoiesis in 23-year-old patients diagnosed of congenital dyserythropoietic anemia.
Anemia ; Anemia, Dyserythropoietic, Congenital* ; Blood Transfusion ; Erythroblasts ; Hematologic Diseases ; Hematopoiesis ; Hematopoiesis, Extramedullary* ; Humans ; Parturition ; Rare Diseases ; Young Adult

OBJECTIVETo report novel mutations SEC23B gene in congenital dyserythropoietic anemia (CDA).

METHODSBy direct sequencing method, we sequenced CDAN1 and SEC23B genes in a Chinese CDA II patient, presented with chronic fatigue and dark urine, as well as his family members. Serum hepcidin was assayed by mass spectrometry.

RESULTSWe found a c.71G>A mutation and a c.74C> A mutation in the patient. In addition, a heterozygous c.55A>G mutation of HFE2 gene was found in some family members. The level of serum hepcidin of the patient was below the detection limit (<1 nmol/L).

CONCLUSIONContrary with what have been reported previously in the Europe, especially in the Italy, the gene mutations identified in this case was different and novel. The two novel mutations contribute to the diagnosis of CDAII and are the first report in East Asian CDAII patients.

Adolescent ; Adult ; Anemia, Dyserythropoietic, Congenital ; genetics ; Asian Continental Ancestry Group ; genetics ; GPI-Linked Proteins ; genetics ; Glycoproteins ; genetics ; Hepcidins ; blood ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Vesicular Transport Proteins ; genetics

OBJECTIVETo investigate the clinical and laboratory features of congenital dyserythropoietic anemia type II (CDA-II) in order to improve the recognition of the disease.

METHODSA case of CDA-II was reported and the related literatures were reviewed.

RESULTSThe 32-years old female presented with moderate anemia, jaundice and hepatosplenomegaly from her childhood and was misdiagnosed as hereditary spherocytosis for a long time. There were no increased reticulocytes in the peripheral blood and her bone marrow showed erythroid hyperplasia with 43% of binucleated erythroblasts. Electron microscopy examination revealed stretches of double membrane lining the inner surface of the erythroblast cell membrane.

CONCLUSIONSCDA-II is a rare congenital anemia characterized by ineffective erythropoiesis with unique laboratory features, and is relatively easy to be misdiagnosed. It is necessary to improve the awareness of CDA-II, and to set-up its responsible gene analysis, i.e., CDAN2 gene and SEC23B gene detection.

Adult ; Anemia, Dyserythropoietic, Congenital ; diagnosis ; genetics ; Female ; Humans ; Vesicular Transport Proteins ; genetics

OBJECTIVETo analyze the clinical and laboratory features of patients with congenital dyserythropoietic anemia type I (CDA-I), and improve the clinical diagnostic accuracy.

METHODSThe clinical and hematological features of 5 patients diagnosed as CDA-I in our hospital between July 2002 and July 2007 were analyzed retrospectively, and the related literatures was reviewed.

RESULTSFive CDA-I patients, 1 male and 4 females, all had a long history of varied degree of chronic anemia. One patient had congenital malformations, 3 jaundice and 4 hepatosplenomegaly. Bone marrow specimens invariably showed hypercellularity due to erythroid hyperplasia with megaloblastic changes, irregularly shaped nuclear, and chromatin bridges in 0.2% to 0.6% of all erythroblasts. All the 5 patients' bone marrow erythroblasts showed spongy heterochromatin appearances (swiss-cheese) with electron microscopy examination. There was no morphologic abnormality in the granulocytes and megakaryocytes. Serum ferritin levels were increased in 3/4 patients. One patient had been misdiagnosed as hereditary spherocytosis and performed splenectomy in the local hospital with no improvement in Hb level.

CONCLUSIONSCDA-I is a rare congenital anemia characterized by ineffective erythropoiesis, jaundice, hepatosplenomegaly and iron overload, and may be misdiagnosed. Keeping these manifestations in mind should avoid misdiagnosis.

Adolescent ; Adult ; Anemia, Dyserythropoietic, Congenital ; blood ; diagnosis ; Female ; Humans ; Male ; Retrospective Studies ; Young Adult

The study was aimed to investigate the ultranstructural feature and diagnostic criteria of congenital dyserythropoietic anemia-type I (CDA-type I). Nucleated red cells in bone marrow from two patients with CDA-type I were analyzed by transmission electron microscopy (TEM). The results indicated that the erythropoietic/granulopoietic ratio was markedly increased with megaloblastic morphology in all stage of erythrocyte. Most proerythroblast showed of irregular nuclei, while the Swiss-cheese-appearance of the heterochromatin was usually found in basophilic and polychromatic erythroblast. About half of orthochromatic erythroblast illustrated karyolysis and karyorrhexis. Some orthochromatic erythroblast exhibited karyolysis and plasmolysis simultaneously. The inter-nuclear chromatin bridge between separated erythroblasts was seldom found by TEM. The nuclear membrane and rough endoplasmic reticulum were destructed at all stage of erythrocytes in different degree. In conclusion, the megaloblastic erythrosis was the main characteristic of CDA-type I, and then nuclear membrane disruption in polychromatic erythroblast and karyolysis or karyorrhexis in orthochromatic erythroblast. The universal breakdown of cytoplasm membranous system was fundamental pathogenesis of CDA-type I.
Anemia, Dyserythropoietic, Congenital ; blood ; pathology ; Bone Marrow Examination ; Erythroblasts ; ultrastructure ; Erythrocytes ; ultrastructure ; Female ; Humans ; Infant ; Iron ; blood ; Male ; Microscopy, Electron, Transmission