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