Background: Majeed syndrome is a rare, autosomal recessive autoinflammatory disorder first described in 1989. The syndrome starts during infancy with recurrent relapses of osteomyelitis typically associated with fever, congenital dyserythropoietic anemia (CDA), and often neutrophilic dermatosis. Mutations in the LPIN2 gene located on the short arm of chromosome 18 have been identified as being responsible for Majeed syndrome. Case presentation: We report an 8-month-old boy, who presented with recurrent fever, mild to moderate anemia, and severe neutropenia. Erythrocyte sedimentation rate and C-reactive protein were elevated. Molecular testing identified a paternal splicing donor site variant c.2327 + 1G > C and a maternal frameshift variant c.1691_1694delGAGA (Arg564Lysfs*3) in LPIN2. Conclusions: Only a few cases with LPIN2 mutation have been reported, mainly in the Middle East with homozygous variants. Our patient exhibited a mild clinical phenotype and severe neutropenia, different from previous reports.

Background: Dilated cardiomyopathy (DCM), which is a major cause of heart failure, is a primary cardiac muscle disease with high morbidity and mortality rates. DCM is a genetically heritable disease and more than 10 gene ontologies have been implicated in DCM. CDH2 encodes N-cadherin and belongs to a superfamily of transmembrane proteins that mediate cell–cell adhesion in a calcium-dependent manner. Deficiency of CDH2 is associated with arrhythmogenic right ventricular cardiomyopathy (OMIM: 618920) and agenesis of the corpus callosum, cardiac, ocular, and genital syndrome (OMIM: 618929). However, there have been no reports of isolated DCM associated with CDH2 deficiency.Methods: We performed whole exome sequencing in a 12-year-old girl with non-syndromic DCM and her unaffected parents. Variants in both known DCM-related genes and novel candidate genes were analyzed and pathogenicity confirmation experiments were performed.Results: No pathogenic/likely pathogenic variant in known DCM-related genes was identified in the patient. We found a de novo variant in a candidate gene CDH2 in the patient, namely, c.474G>C/p.Lys158Asn (NM_001792.5). This variant has not been reported in the ClinVar or Human Gene Mutation Database (HGMD). CDH2 p.Lys158Asn was found in the conserved domain of N-cadherin, which is associated with the hydrolysis of the precursor segment and interference with adhesiveness. Furthermore, we tested the expression and efficiency of cell–cell adhesion while overexpressing the CDH2 Lys158Asn mutant and two previously reported variants in CDH2 as positive controls. The adhesion efficiency was considerably reduced in the presence of the mutated CDH2 protein compared with wild-type CDH2 protein, which suggested that the mutated CDH2 protein's adhesion capacity was impaired. The variant was probably pathogenic after integrating clinical manifestations, genetic analysis, and functional tests.Conclusion: We identified a CDH2 variant in DCM. We observed a new clinical symptom associated with N-cadherin deficiency and broadened the genetic spectra of DCM.