Understanding the pathophysiological mechanism of Mulvihill-Smith syndrome global patient-13 using sc-MULTI-omics approach: a case report

Mulvihill-Smith syndrome (MSS) is an extremely rare disorder and currently 12 persons have been described in the literature. Most of the reported cases (91%) have immunological impairments and these patients succumb to infection or later in their life develop cancer. Pathophysiology remains elusive and therapeutic options are limited. Here, we report a 13th MSS case who is only 16 years old which has increased leukocyte counts, xeroderma pigmentosa and accelerated ageing. Progress in single-cell RNA sequencing (sc-RNA-seq) coupled with antibody detection, TCR and BCR provides an opportunity to dissect human disease pathophysiology at exceptional resolutions for ultra-rare diseases lacking animal models. We performed sc-MULTI-omics RNA-seq from MSS patient blood samples (peripheral blood mononuclear cells; PBMCs), identifying the pathways with progeria-like phenotype and cancer progression as a potential target. We further showed that central memory CD4+ T cells and effector memory CD8+ T cells were enriched compared with mother. Thus, sc-MUTLI-omics RNA-seq analyses improve our understanding of complicated human disease pathophysiology and provide an alternative approach in personalized medicine if any drug therapy was provided for such cases.