一例PTEN新生杂合突变患儿临床表型与免疫特征分析

邱璐瑶; 唐文静; 杨露; 吕格; 陈俊杰; 孙淦; 王艳平; 周丽娜; 安云飞; 张志勇; 唐雪梅; 赵晓东; 杜鸿强

doi:10.12290/xhyxzz.2023-0023

一例PTEN新生杂合突变患儿临床表型与免疫特征分析

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

摘要

摘要:
目的探讨一例PTEN杂合突变患儿的临床表型及免疫特征，丰富PTEN突变相关临床表型谱。
方法收集患儿门诊及住院期间的病史资料、生化检查及影像学检查结果，抽取外周静脉血进行医学全外显子组综合检测，Sanger测序验证患儿及其父母PTEN基因突变位点，采用流式细胞术进行T细胞PI3K/Akt/mTOR通路磷酸化水平及T细胞亚群与其耗竭相关表面分子检测，采用蛋白质印迹法检测外周血单个核细胞PTEN蛋白表达水平，健康对照为患儿父亲。
结果患儿以大头畸形(头围＞P99)、疣状表皮痣、精神运动发育迟缓、学语延迟为主要临床表现，PTEN基因(NM_000314.8) c.388C＞T(p.R130X)新生杂合突变，PTEN蛋白表达减少，血清IgA水平稍低(0.177 g/L)，精细免疫分型CD4⁺终末分化效应记忆T细胞、CD8⁺终末分化效应记忆T细胞、过渡性B细胞比例及绝对数均增加，但T细胞PI3K/Akt/mTOR通路磷酸化水平正常。患儿以PTEN错构瘤综合征相关表型为主要表现，无明显PI3Kδ过度活化综合征样表型。
结论该患儿PTEN基因的突变位点为国内首例，有助于丰富临床医生对该疾病的认识，提高诊治水平。

Abstract:
Objective 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.
Methods 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.
Results 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.
Conclusions 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.

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