Objective: To report the clinical manifestations and total exon detection results of one case of MYSM1 gene complex heterozygosity mutation of bone marrow failure syndrome 4 and the results of total exon detection of her family to provide a case phenotype for the early diagnosis of bone marrow failure syndrome 4. Methods: A 1-month-old girl with severe anemia was sequenced with trio-WES. Similarly, the family was also sequenced with tribe-WES to confirm the molecular diagnosis. BWA, GATK, and other software were used for annotation analysis of sequencing results. After polymerase chain reaction, Sanger sequencing was performed by ABI3730 sequencer to verify the target sequence. Moreover, the verification results were obtained by the sequence analysis software. The clinical diagnosis of this girl was reported and the relevant pieces of literature were reviewed. Results: The girl presented with pancytopenia, polydactylism, nonspecific white matter changes, and cysts. However, CD3(-)CD19(+) B decreased. The child was identified with MYSM1 complex heterozygous mutation by whole-exome sequencing, NM_001085487.2:c.1607_c.1611delAAGAG and c.1432C>T, which was respectively inherited from his parents. Genealogy verification confirmed that the c.1432C>T mutation carried by the father was from the grandfather (father's father) , whereas the c.1607_c.1611delAAGAG mutation carried by the mother was from the grandfather (mother's father) , whereas the grandmothers, aunts, and uncle did not carry the mutation. The child was diagnosed with BMFS4 combined with clinical phenotypic and molecular genetic findings. Conclusion: This case provides a case phenotype for the early diagnosis of BMFS4 and extends the pathogenicity variation and phenotype spectrum of the MYSM1 gene. The newly discovered pathogenic variant of MYSM1 c. 1607_c.1611delAAGAG has not been reported at home or abroad.
目的： 报道1例MYSM1基因复合杂合变异致骨髓衰竭综合征4型患儿临床表现及全外显子检测结果，同时报道其家系全外显子检测结果，为早期诊断此类骨髓衰竭综合征提供典型案例。 方法： 报道1例1月龄骨髓衰竭综合征4型患儿临床诊断过程，并对患儿及其家系成员外周血DNA进行全外显子测序，使用BWA、GATK等软件对测序结果进行注释分析。 结果： 本例1月龄骨髓衰竭综合征4型患儿，表现为全血细胞减少、多指畸形，影像学示非特异性脑白质改变及囊肿，淋巴细胞亚群分类示CD3(-)CD19(+) B细胞降低。通过家系全外显子测序检测，鉴定患儿携带分别遗传自父母的MYSM1基因复合杂合性变异NM_001085487.2:c.1607_c.1611delAAGAG和c.1432C>T。家系验证证实先证者父亲携带的c.1432C>T突变来源于先证者祖父，先证者母亲携带的c.1607_c.1611delAAGAG突变来自于先证者外祖父，其他家系成员均不携带突变。 结论： 本研究新发现MYSM1致病性变异c.1607_c.1611delAAGAG，国内外尚未见报道。本例为BMFS4的早期诊断提供了典型案例，并扩展了MYSM1基因致病性变异谱和表型谱。.
Keywords: Bone marrow failure syndrome type 4; Family survey; MYSM1 mutation.