Abstract:

Objective To investigate the clinical and immunological features of Griscelli syndrome type 2 (GS2) caused by RAB27A gene defect. Methods The clinical data, biochemical examination and pathological biopsy results of 2 children with GS2 in 1 family were collected. Hair was collected for microscopic examination. Peripheral venous blood was extracted for immune-related gene sequencing, and the RAB27A mutation site in the children and their parents was verified by Sanger sequencing. The expression level of RAB27A protein in peripheral blood mononuclear cells was detected by western blot. Flow cytometry was performed to detect CD107a expression in NK and CTL cells, and an age-matched healthy child was used as control. Results The two patients were siblings, and both presented with postnatal hypopigmentation of hair. The main clinical manifestations of both patients were recurrent fever, recurrent respiratory infection combined with hemophagocytic lymphohistiocytosis (HLH), and the younger sister was accompanied by generalized diffuse target-shaped lesions. Accumulation of irregular melanin clusters in the hair were observed in both patients, and the histopathology of the younger sister's lesions showed an irregular distribution of melanocytes in the basal layer of the epidermis. Gene sequencing identified a homozygous frameshift mutation of c.377delC in exon 5 of RAB27A gene, and the parents were consanguineous and both were carriers. Reduced expression of RAB27A protein and defects in the cytotoxicity of NK cells and CTL were observed in peripheral blood mononuclear cells of both patients. Neither patient received chemotherapy or hematopoietic stem cell transplantation (HSCT) and died of HLH successively. Conclusions The definitive diagnosis of GS2 relies on clinical manifestations and genetic testing, immune function testing also contributes to the diagnosis. Currently, allogeneic HSCT is the only method to cure GS2.

Key words: Griscelli syndrome type 2, RAB27A gene, familial hemophagocytic lymphohistiocytosis