A novel homozygous missense variant in syndromic juvenile-onset diabetes.

OBJECTIVES

The gene encodes a protein that acts as a cochaperone of binding immunoglobulin protein (BiP), a major member of the heat shock protein 70 (HSP70) family, which is found in the endoplasmic reticulum (ER) and promotes normal protein folding. Loss-of-function mutations in lead to early-onset diabetes and multisystemic neurodegeneration. In this article, we report a case of monogenic syndromic diabetes caused by a previously undescribed variant.

CASE PRESENTATION

A 15-year-old 5-month-old girl with polyuria and polydipsia for the last 2-3 months was diagnosed and treated as diabetic ketoacidosis at the center where she was admitted with complaints of general condition disorder and frequent breathing. Her laboratory findings were HbA 15.1 %, serum insulin 7.83 m U/L, C-peptide 0.78 μg/L. Tests for autoimmune diabetes markers were negative. Physical examination revealed severe short stature 141.4 cm (-3.62 SDS). Sensorineural hearing loss developed 5 months after the diagnosis of diabetes and intellectual functions were impaired. Neurologic examination revealed marked ataxia. Monogenic syndromic diabetes mellitus with multisystemic neurodegeneration including juvenile onset diabetes mellitus, ataxia, short stature and sensorineural hearing loss was considered. Exome sequencing and CNV (Copy Number Variation) analysis revealed a novel homozygous c.1244G>C (p.Arg415Pro) variant in gene.

CONCLUSIONS

This case supports the wide phenotypic spectrum and multisystem involvement potential of variants and demonstrates the need to increase awareness in the diagnostic process of these rare genetic disorders..