QIU Luyao, TANG Wenjing, YANG Lu, LYU Ge, CHEN Junjie, SUN Gan, WANG Yanping, ZHOU Lina, AN Yunfei, ZHANG Zhiyong, TANG Xuemei, ZHAO Xiaodong, DU Hongqiang. Clinical Phenotype and Immunological Characteristics of A Patient with De Novo Heterozygous Mutation of PTEN[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(2): 373-378. DOI: 10.12290/xhyxzz.2023-0023
Citation: QIU Luyao, TANG Wenjing, YANG Lu, LYU Ge, CHEN Junjie, SUN Gan, WANG Yanping, ZHOU Lina, AN Yunfei, ZHANG Zhiyong, TANG Xuemei, ZHAO Xiaodong, DU Hongqiang. Clinical Phenotype and Immunological Characteristics of A Patient with De Novo Heterozygous Mutation of PTEN[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(2): 373-378. DOI: 10.12290/xhyxzz.2023-0023

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

Funds: 

National Natural Science Foundation of China 81974255

More Information
  • Corresponding author:

    ZHAO Xiaodong, E-mail: zhaoxd530@aliyun.com

    DU Hongqiang, E-mail: doctordo@aliyun.com

  • Received Date: January 08, 2023
  • Accepted Date: February 09, 2023
  • Available Online: March 20, 2023
  • Issue Publish Date: March 29, 2023
  •   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.
  • [1]
    Pilarski R. PTEN Hamartoma Tumor Syndrome: A Clinical Overview[J]. Cancers (Basel), 2019, 11: 844. DOI: 10.3390/cancers11060844
    [2]
    Celebi JT, Tsou HC, Chen FF, et al. Phenotypic findings of Cowden syndrome and Bannayan-Zonana syndrome in a family associated with a single germline mutation in PTEN[J]. J Med Genet, 1999, 36: 360-364.
    [3]
    Tsujita Y, Mitsui-Sekinaka K, Imai K, et al. Phosphatase and tensin homolog (PTEN) mutation can cause activated phosphatidylinositol 3-kinase δ syndrome-like immunodeficiency[J]. J Allergy Clin Immunol, 2016, 138: 1672-1680. DOI: 10.1016/j.jaci.2016.03.055
    [4]
    Ding Y, Zhou L, Xia Y, et al. Reference values for peripheral blood lymphocyte subsets of healthy children in China[J]. J Allergy Clin Immunol, 2018, 142: 970-973. DOI: 10.1016/j.jaci.2018.04.022
    [5]
    Pilarski R, Burt R, Kohlman W, et al. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria[J]. J Natl Cancer Inst, 2013, 105: 1607-1616. DOI: 10.1093/jnci/djt277
    [6]
    Daly MB, Pilarski R, Berry M, et al. NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2017[J]. J Natl Compr Canc Netw, 2017, 15: 9-20. DOI: 10.6004/jnccn.2017.0003
    [7]
    Busa T, Milh M, Degardin N, et al. Clinical presentation of PTEN mutations in childhood in the absence of family history of Cowden syndrome[J]. Eur J Paediatr Neurol, 2015, 19: 188-192. DOI: 10.1016/j.ejpn.2014.11.012
    [8]
    Coulter TI, Chandra A, Bacon CM, et al. Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study[J]. J Allergy Clin Immunol, 2017, 139: 597-606. DOI: 10.1016/j.jaci.2016.06.021
    [9]
    Larbi A, Fulop T. From "truly naïve" to "exhausted senescent" T cells: when markers predict functionality[J]. Cytometry A, 2014, 85: 25-35. DOI: 10.1002/cyto.a.22351
    [10]
    Hand TW, Cui W, Jung YW, et al. Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival[J]. Proc Natl Acad Sci USA, 2010, 107: 16601-16606. DOI: 10.1073/pnas.1003457107
    [11]
    Zhou Y, Zhang Y, Han J, et al. Transitional B cells involved in autoimmunity and their impact on neuroimmunological diseases[J]. J Transl Med, 2020, 18: 131. DOI: 10.1186/s12967-020-02289-w
    [12]
    Leslie NR, Longy M. Inherited PTEN mutations and the prediction of phenotype[J]. Semin Cell Dev Biol, 2016, 52: 30-38. DOI: 10.1016/j.semcdb.2016.01.030
    [13]
    Chen L, Guo D. The functions of tumor suppressor PTEN in innate and adaptive immunity[J]. Cell Mol Immunol, 2017, 14: 581-589. DOI: 10.1038/cmi.2017.30
    [14]
    Nelen MR, van Staveren WC, Peeters EA, et al. Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease[J]. Hum Mol Genet, 1997, 6: 1383-1387. DOI: 10.1093/hmg/6.8.1383
    [15]
    Mester J, Eng C. Cowden syndrome: recognizing and managing a not-so-rare hereditary cancer syndrome[J]. J Surg Oncol, 2015, 111: 125-130. DOI: 10.1002/jso.23735
    [16]
    Daly MB, Pilarski R, Yurgelun MB, et al. NCCN Guide-lines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020[J]. J Natl Compr Canc Netw, 2020, 18: 380-391. DOI: 10.6004/jnccn.2020.0017
    [17]
    Podsypanina K, Lee RT, Politis C, et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice[J]. Proc Natl Acad Sci USA, 2001, 98: 10320-10325. DOI: 10.1073/pnas.171060098
    [18]
    Squarize CH, Castilho RM, Gutkind JS. Chemoprevention and treatment of experimental Cowden's disease by mTOR inhibition with rapamycin[J]. Cancer Res, 2008, 68: 7066-7072. DOI: 10.1158/0008-5472.CAN-08-0922
    [19]
    Ross-Innes CS, Becq J, Warren A, et al. Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma[J]. Nat Genet, 2015, 47: 1038-1046. DOI: 10.1038/ng.3357
    [20]
    Lagergren J, Lagergren P. Recent developments in esophageal adenocarcinoma[J]. CA Cancer J Clin, 2013, 63: 232-248. DOI: 10.3322/caac.21185
  • Related Articles

    [1]YAO Ru, YANG Xu, QU Yang, LIAN Jie, ZHANG Jiahui, HUANG Xin, CHEN Chang, REN Xinyu, PAN Bo, ZHOU Yidong, SUN Qiang. PTEN Mutation Related Unilateral Multicentric, Synchronous and Metachronous Bilateral Breast Cancer: Three Case Reports[J]. Medical Journal of Peking Union Medical College Hospital, 2024, 15(4): 916-920. DOI: 10.12290/xhyxzz.2023-0550
    [2]CHEN Yuqing, LI Jinming. Virological Characteristics of the Omicron Variant: Key Mutations, Pathogenicity, and Immune Escape[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(5): 945-952. DOI: 10.12290/xhyxzz.2023-0139
    [3]LI Wendao, GU Hao, WANG Wei, WU Runhui, SONG Hongmei. First Case Report of FOXN1 Haploinsufficiency in China and Literature Review[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(2): 366-372. DOI: 10.12290/xhyxzz.2022-0040
    [4]Xiao-yun ZHANG, Jian-yu HAO. PTEN and Digestive Organ Fibrosis[J]. Medical Journal of Peking Union Medical College Hospital, 2017, 8(4-5): 300-304. DOI: 10.3969/j.issn.1674-9081.2017.05.020
    [5]Jing-yi LI, Li-jun XU, Yan JIANG, Zheng-qing QIU, Feng-xia YAO, Wen-hui LI, Xin-hua XIAO, Xiao-ping XING. A Novel Compound Heterozygous Mutation in Glucose-6-Phosphatase Gene in a Chinese Patient with Glycogen Storage Disease Ia[J]. Medical Journal of Peking Union Medical College Hospital, 2016, 7(4): 264-268. DOI: 10.3969/j.issn.1674-9081.2016.04.005
    [6]MAIMAITI Nu-rong-gu-li, Hua-bing ZHANG, Xiao-ping XING. Clinical and Genetic Analysis of a Uyghur Patient with Gitelman's Syndrome[J]. Medical Journal of Peking Union Medical College Hospital, 2015, 6(6): 427-431. DOI: 10.3969/j.issn.1674-9081.2015.06.006
    [7]Xiao-jie XU, Dou-dou MA, Fang Lü, Yi LIU, Jian-yi WANG, Yan JIANG, Ou WANG, Wei-bo XIA, Xiao-ping XING, Mei LI. Mutation in TGFB1 Causes Rare Progressive Diaphyseal Dysplasia[J]. Medical Journal of Peking Union Medical College Hospital, 2015, 6(5): 327-332. DOI: 10.3969/j.issn.1674-9081.2015.05.003
    [8]Bei TAN, Yun-lu FENG, Dong WU, Yi-cheng ZHU, Yu CHEN, Jia-ming QIAN. Mitochondrial Neurogastrointestinal Encephalomyopathy Caused by A Novel TYMP Gene Mutation in An Adult Patient[J]. Medical Journal of Peking Union Medical College Hospital, 2014, 5(3): 302-306. DOI: 10.3969/j.issn.1674-9081.2014.03.011
    [9]Fei XU, Rui-fang SUI, Hui LI, Ru-xin JIANG, Fang-tian DONG. Clinical Characteristics and Genetic Mutations of Chinese Patients with X-linked Retinoschisis[J]. Medical Journal of Peking Union Medical College Hospital, 2013, 4(2): 98-103. DOI: 10.3969/j.issn.1674-9081.2013.02.003
    [10]Xu ZHANG, Yong-sheng TIAN, Xiao-wei CHEN, Hong JIANG. Mitochondrial 12S rRNA Mutations Related to Drug-induced Hearing Loss[J]. Medical Journal of Peking Union Medical College Hospital, 2012, 3(2): 185-189. DOI: 10.3969/j.issn.1674-9081.2012.02.012
  • Cited by

    Periodical cited type(1)

    1. 徐丹,张丽,朱芸. 肿瘤患者PICC导管相关血流感染mTOR 信号通路变化与危险因素. 中华医院感染学杂志. 2023(23): 3567-3571 .

    Other cited types(0)

Catalog

    Article Metrics

    Article views (3003) PDF downloads (40) Cited by(1)
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return
    x Close Forever Close