Gao-Hui Cao, Lv Liu, Zhen Liu, Lei Zhu, Na Ta, Yi-Hui Liu, Ai-Qian Zhang, Liang-Liang Fan
Members of the immunoglobulin superfamily (IgSF) are cell-surface proteins essential for a wide range of biological processes, including molecular transport, morphoregulation, and cell differentiation. IGSF10, a member of this family, has been identified as a disease-associated gene in delayed puberty and cleidocranial dysplasia. In this study, a Chinese patient with delayed puberty, microcephaly, scoliosis, and epilepsy was investigated. The genetic defect and immune alterations were assessed using whole-exome sequencing, Sanger sequencing, and single-cell RNA sequencing. After variant filtering, a novel IGSF10 variant, NM_178,822.5:c.4518del (p.His1506Gln fs Ter13), was identified in the proband. Sanger sequencing indicated that this variant was de novo, as it was present only in the proband and absent from her parents. Quantitative real-time PCR showed that the newly identified variant was associated with reduced IGSF10 mRNA abundance, consistent with nonsense-mediated decay. Single-cell RNA sequencing of peripheral blood mononuclear cells revealed that this variant was associated with marked alterations in effector T-cell and monocyte populations. Further analysis suggested altered differentiation patterns of T cells and monocytes, supporting the hypothesis that immune perturbations may contribute to the patient's reproductive, neurological, and skeletal phenotypes, although this possibility requires functional validation. A novel IGSF10 variant was identified in a Chinese patient with delayed puberty, microcephaly, scoliosis, and epilepsy. This case expands the mutational spectrum of IGSF10 deficiency and suggests that its phenotypic spectrum may include scoliosis and epilepsy, pending further confirmation. These findings also provide preliminary insight into the potential interplay among IGSF10, immune function, hormone secretion, and brain and skeletal development.