Mengen Eda, Kor Deniz, Bulut Fatma Derya, Kotan Leman Damla, Turan İhsan, Yüksel Bilgin, Mungan Neslihan Önenli
Department of Pediatric Endocrinology, Faculty of Medicine, Çukurova University, 01330, Adana, Türkiye.
Department of Pediatric Metabolism and Nutrition, Çukurova University Faculty of Medicine, Adana, Türkiye.
J Pediatr Endocrinol Metab. 2025 Jun 20;38(9):991-995. doi: 10.1515/jpem-2025-0072. Print 2025 Sep 25.
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.
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.
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..
该基因编码一种蛋白质，作为结合免疫球蛋白蛋白（BiP）的共伴侣蛋白，BiP是热休克蛋白70（HSP70）家族的主要成员，存在于内质网（ER）中，促进正常蛋白质折叠。该基因功能丧失突变会导致早发性糖尿病和多系统神经退行性变。在本文中，我们报告了一例由先前未描述的该基因变异引起的单基因综合征性糖尿病病例。
一名15岁5个月大的女孩，在过去2至3个月出现多尿和多饮症状，因全身状况不佳和呼吸频繁等主诉入院，在该中心被诊断并治疗为糖尿病酮症酸中毒。她的实验室检查结果为糖化血红蛋白（HbA）15.1%，血清胰岛素7.83 mU/L，C肽0.78 μg/L。自身免疫性糖尿病标志物检测为阴性。体格检查发现严重身材矮小，身高141.4 cm（标准差分值-3.62）。糖尿病诊断后5个月出现感音神经性听力损失，智力功能受损。神经学检查显示明显共济失调。考虑为单基因综合征性糖尿病伴多系统神经退行性变，包括青少年型糖尿病、共济失调、身材矮小和感音神经性听力损失。外显子组测序和拷贝数变异（CNV）分析显示该基因存在一个新的纯合c.1244G>C（p.Arg415Pro）变异。
该病例支持了该基因变异广泛的表型谱和多系统受累潜力，并表明在这些罕见遗传疾病的诊断过程中需要提高认识。
