A novel compound heterozygous mutation of MYSM1 gene in a patient with bone marrow failure syndrome 4.

Myb-like swirm and MPN domains 1 (MYSM1) is a gene encoding histone H2A deubiquitinase, which can regulate the expression of transcription factor related genes and involve the immune and hematopoietic system. Homozygous and missense mutations of MYSM1 lead to immune deficiency, mainly manifested by B cell deficiency and T cell reduction. Bone marrow failure syndrome 4 (BMFS 4) is an autosomal recessive disorder characterized by early-onset anemia, leukopenia, and decreased B cells, resulting in an increased susceptibility to infection. Here, we report a 2-month-old girl with a highly suspected BMFS due to the clinical characteristics of recurrent, severe anemia, intermittent thrombocytopenia, polydactylism, and slow growth. Whole exome sequencing identified a compound heterozygous mutation with c.1607_c.1611delAAGAG (exon 12) from the mother and c.1432C>T (exon 10) from the father in the girl. We suggest that c.1607_c.1611delAAGAG is a newly discovered pathogenic mutation. In addition, the mutation c.1432C>T (exon 10), rs748065332 is a truncated mutation (p.R478*,351), which is also reported for the first time. This case expands the phenotypic spectrum of BMSF4 and is helpful to explore the significance of BMFS4 gene detection in children with bone marrow failure syndrome.