Journal of Shandong University (Health Sciences) ›› 2022, Vol. 60 ›› Issue (5): 104-108.doi: 10.6040/j.issn.1671-7554.0.2021.1523

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A case report of early-onset diabetes mellitus carrying paired box 4 gene mutation and literature review

TANG Qinlian1, ZHANG Yuchao1, ZHAO Huichen1, MA Xiaoli1, YU Minmin1, LIU Yuantao2   

  1. 1. Department of Endocrinology, Qingdao Municipal Hospital, Qingdao 266011, Shandong, China;
    2. Department of Endocrinology, Qilu Hospital of Shandong University(Qingdao), Qingdao 266011, Shandong, China
  • Published:2022-06-01

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Abstract: Objective To explore the clinical features of early-onset diabetes caused by paired box 4(PAX4)gene mutation so as to improve the understanding of the disease. Methods The clinical data of a patient with early-onset diabetes mellitus with PAX4 gene mutation were retrospectively analyzed, and the literature was reviewed. Results A 25-year-old female patient was admitted due to fatigue, thirst, polydipsia and polyuria for more than 40 days, and nausea and anorexia for 4 days. The diagnosis was diabetic ketoacidosis. Insulin autoantibody test was negative. During hospitalization, the patient was treated with a variety of hypoglycemic drugs, but with poor curative effects and islet secretion failure. Genetic testing revealed a heterozygous variant of G > A at codon 192(CGT)in exon 5 of PAX4 gene, which was R192H. Conclusion For patients with suspected monogenic diabetes, gene sequencing is of great significance, especially in the diagnosis and typing. Accurate genetic diagnosis can assure professional treatment.

Key words: Diabetes, Gene sequencing, Paired box 4 genes, Mutation

CLC Number: 

  • R587
[1] Fajans SS, Bell GI. MODY: history, genetics, pathophysiology, and clinical decision making [J]. Diabetes Care, 2011, 34(8): 1878-1884.
[2] Gupta MK, Vadde R. A computational structural biology study to understand the impact of mutation on structure-function relationship of inward-rectifier potassium ion channel Kir6.2 in human [J]. J Biomol Struct Dyn, 2021, 39(4): 1447-1460.
[3] Nkonge KM, Nkonge DK, Nkonge TN. The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young(MODY)[J]. Clin Diabetes Endocrinol, 2020, 6(1): 20.
[4] Jang KM. Maturity-onset diabetes of the young: update and perspectives on diagnosis and treatment [J]. Yeungnam Univ J Med, 2020, 37(1): 13-21.
[5] Xu Y, Wang L, He J, et al. Prevalence and control of diabetes in Chinese adults[J]. JAMA, 2013, 310(9): 948-959.
[6] Al-Kandari H, Al-Abdulrazzaq D, Davidsson L, et al. Maturity-onset diabetes of the young(MODY): a time to act [J]. Lancet Diabetes Endocrinol, 2020, 8(7): 565-566.
[7] Sosa-Pineda B. The gene Pax4 is an essential regulator of pancreatic beta-cell development [J]. Mol Cells, 2004, 18(3): 289-294.
[8] Perge K, Eljaafari A. Overexpression of PAX4 by gene therapy for type 1 diabetes treatment [J]. Med Sci(Paris), 2020, 36(5): 458-460.
[9] Xu YY, Wang Y, Song YN, et al. Generation and phenotype identification of PAX4 gene knockout rabbit by CRISPR/Cas9 system [J]. G3(Bethesda), 2018, 8(8): 2833-2840.
[10] Sosa-Pineda B, Chowdhury K, Torres M, et al. The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas [J]. Nature, 1997, 386(6623): 399-402.
[11] Brun T, Franklin I, St-Onge L, et al. The diabetes-linked transcription factor PAX4 promotes beta-cell proliferation and survival in rat and human islets [J]. J Cell Biol, 2004, 167(6): 1123-1135.
[12] Lu J, Li G, Lan MS, et al. Pax4 paired domain mediates direct protein transduction into mammalian cells [J]. Endocrinology, 2007, 148(11): 5558-5565.
[13] Hu He KH, Lorenzo PI, Brun T, et al. In vivo conditional Pax4 overexpression in mature islet β-cells prevents stress-induced hyperglycemia in mice [J]. Diabetes, 2011, 60(6): 1705-1715.
[14] Mellado-Gil JM, Jimenez-Moreno CM, Martin-Montalvo A, et al. PAX4 preserves endoplasmic reticulum integrity preventing beta cell degeneration in a mouse model of type 1 diabetes mellitus [J]. Diabetologia, 2016, 59(4): 755-765.
[15] Collombat P, Xu X, Ravassard P, et al. The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells [J]. Cell, 2009, 138(3): 449-462.
[16] Lorenzo PI, Juárez-Vicente F, Cobo-Vuilleumier N, et al. The diabetes-linked transcription factor PAX4: from gene to functional consequences [J]. Genes(Basel), 2017, 8(3): 101.
[17] Plengvidhya N, Kooptiwut S, Songtawee N, et al. PAX4 mutations in Thais with maturity onset diabetes of the young [J]. J Clin Endocrinol Metab, 2007, 92(7): 2821-2826.
[18] Abreu GM, Soares CAPD, Tarantino RM, et al. Identification of the first PAX4-MODY family reported in Brazil[J]. Diabetes Metab Syndr Obes, 2020, 13: 2623-2631. doi:10.2147/dmso.s256858.
[19] Mauvais-Jarvis F, Smith SB, May CL, et al. PAX4 gene variations predispose to ketosis-prone diabetes [J]. Hum Mol Genet, 2004, 13(24): 3151-3159.
[20] Shimajiri Y, Shimabukuro M, Tomoyose T, et al. PAX4 mutation(R121W)as a prodiabetic variant in Okinawans [J]. Biochem Biophys Res Commun, 2003, 302(2): 342-344.
[21] Sujjitjoon J, Kooptiwut S, Chongjaroen N, et al. PAX4 R192H and P321H polymorphisms in type 2 diabetes and their functional defects [J]. J Hum Genet, 2016, 61(11): 943-949.
[22] Ang SF, Tan CSH, Wang L, et al. PAX4 R192H is associated with younger onset of Type 2 diabetes in East Asians in Singapore [J]. J Diabetes Complications, 2019, 33(1): 53-58.
[23] Sujjitjoon J, Kooptiwut S, Chongjaroen N, et al. Aberrant mRNA splicing of paired box 4(PAX4)IVS7-1G>A mutation causing maturity-onset diabetes of the young, type 9 [J]. Acta Diabetol, 2016, 53(2): 205-216.
[24] Jo W, Endo M, Ishizu K, et al. A novel PAX4 mutation in a Japanese patient with maturity-onset diabetes of the young [J]. Tohoku J Exp Med, 2011, 223(2): 113-118.
[25] Liang H, Zhang Y, Li M, et al. Recognition of maturity-onset diabetes of the young in China [J]. J Diabetes Investig, 2021, 12(4): 501-509.
[26] Yang Y, Chan L. Monogenic diabetes: what it teaches us on the common forms of type 1 and type 2 diabetes [J]. Endocr Rev, 2016, 37(3): 190-222.
[27] 于晓华, 张金玲, 刘国良. MODY 9的研究,认识现状及处理[J]. 实用糖尿病杂志, 2017, 13(2): 7-9.
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