Clinical Phenotype and Immunological Characteristics of A Patient with De Novo Heterozygous Mutation of PTEN

To analyze the clinical phenotype and immunological characteristics of a patient with heterozygous mutation of PTEN and enrich the clinical phenotypes related to PTEN mutation.

A retrospective analysis of the clinical data of a patient with PTEN heterozygous mutation admitted to the Children's Hospital of Chongqing Medical University was conducted. Peripheral venous blood was extracted for medical whole-exome comprehensive detection, and the PTEN mutation was confirmed by Sanger sequencing. Flow cytometry was applied to detect the lymphocyte subsets and immunophenotype of the patient. The expression level of PTEN protein in peripheral blood mononuclear cells was detected by Western blot, and the healthy control was the patient's father.

The patient was a boy of 1 year and 4 months, with macrocephaly (head circumference > P99), verrucous epidermal nevus, delayed psychomotor development and delayed language learning as the main manifestations. Gene sequencing revealed a de novo heterozygous mutation of PTEN c.388C > T(p.R130X). Reduced expression of PTEN protein was observed in peripheral blood mononuclear cells of the patient. For immunological characteristics, the IgA level mildly decreased(0.177 g/L), with increased counts of terminally differentiated memory CD4⁺ T cells, terminally differentiated memory CD8⁺ T cells, transitional B cells, but phosphorylation of PI3K/Akt/mTOR pathway in T cells was normal. The patient mainly manifested as PTEN hamartoma tumor syndrome related phenotype, without any classic activated phosphatidylinositol 3-kinase δ syndrome-like phenotype.

This patient has a de novo heterozygous mutation of PTEN c.388C > T(p.R130X), which has not been previously reported in China. This article could enrich clinicians' understanding of the disease and assist clinical diagnosis and treatment.