Abstract
Objective: Maturity-onset diabetes of the young (MODY) is a group of monogenic diabetes characterized by an autosomal dominant inheritance. MODY is categorized by a large variety of clinical manifestations and is caused by a wide spectrum of mutations in MODY‑related genes that lead to different clinical pictures and require distinct treatment strategies. In the current study, the clinical features and gene mutations of a Chinese child, diagnosed with MODY9, are reported for the first time with the relevant literature being adequately reviewed. Methods: The clinical data of a PAX4-MODY9 patient admitted to the Department of Endocrinology at Beijing Children’s Hospital are summarized, and his genetic sequencing results are analyzed and discussed. Results: The patient was male, aged 19 months. He was admitted to the hospital due to excessive water drinking, polyuria for over half a month and wheezing for 3 days. Laboratory examination showed that the blood glucose was 21.69mmol/L, glycosylated haemoglobin was 11.1%, the measured levels of insulin on the 0th minute were 0.56μIU/ml, while at the same time point the C-peptide blood serum concentration was 0.09ng/ml. ICA (anti-islet cell antibody) and GADA (anti-glutamate decarboxylase antibody) were negative. Blood gas analysis showed that the blood pH was 7.06, the actual and standard bicarbonate was 4.2mmol/L and 5.8mmol/L, while the whole blood base storage was 24.2mmol/L. Urine routine tests showed that urine glucose and ketone bodies were positive, 4+ and 3+ respectively. The patient was treated with insulin in the meantime. The whole-exon sequencing analysis demonstrated that the child carried the heterozygous missense mutation of c.487>T in the 7th exon region of PAX4 gene, leading to the amino acid sequence variation of p.R163W. The father of the child patient had the same heterozygous mutation, while the mother presented with a normal genotype, suggesting that the mutation was autosomal dominant. Up to now, c.487C>T mutation in the PAX4 gene has not been reported in literature yet. Conclusions: MODY diagnostics by gene sequencing analysis holds great potential for precise and on time therapeutic solutions. Results show that in Chinese children, the rare heterozygous mutation c.487C>T of PAX4 gene leads to the occurrence of MODY9 and though the clinical symptoms of MODY9 are different, we suggest this patient to undergo insulin therapy.
Keywords: MODY9, PAX4 gene, missense mutation, next-generation sequencing, monogenic diabetes