Clinical and genetic analysis of a child with Majeed syndrome / 中华医学遗传学杂志

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.

Variant analysis of SEC23B gene in 4 families with congenital dyserythropoietic anemia / 中华医学遗传学杂志

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.

New mutation site of SEC23B gene in type Ⅱ congenital erythrocythememia anemia: one case report and literatures review / 中华血液学杂志

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.