PDF(Pubmed)
Abstract：
DNAJC3, abundant in the pancreatic cells, attenuates endoplasmic reticulum stress. Homozygous DNAJC3 mutations have been reported to cause non-immune juvenile-onset diabetes, neurodegeneration, hearing loss, short stature, and hypothyroidism.
We report a case of homozygous DNAJC3 mutation in two siblings of a consanguineous family. A 3-year-old boy presented with short stature and a thyroid nodule. Laboratory findings confirmed hypothyroidism. Subsequently, levothyroxine was administered. Growth hormone (GH) stimulation test results were within the normal limits. His stature was exceedingly short (80.5 cm) (-3.79 SDS). The patient developed sensorineural hearing loss at age 6 years; his intellectual functioning was impaired. Recombinant Human Growth Hormine (rhGH) treatment was postponed until the age of 6.9 years due to a strong family history of diabetes. At age 9 years, he developed an ataxic gait. Brain magnetic resonance imaging (MRI) revealed neurodegeneration. The patient developed diabetes at the age of 11 years-5 years after the initiation of rhGH treatment. Tests for markers of autoimmune diabetes were negative. Lifestyle modification was introduced, but insulin therapy was eventually required. Whole-exome-sequencing (WES) revealed a homozygous DNAJC3 mutation, which explained his clinical presentation. MRI revealed a small, atrophic pancreas. At the age of 17, his final adult height was 143 cm (-4.7 SDS). His elder brother, who had the same mutation, had a similar history, except that he had milder ataxia and normal brain MRI finding at the age of 28 years.
We propose that DNAJC3 mutation can be considered as a cause of maturity onset diabetes of the young. Patients with DNAJC3 mutations may possess a small atrophic pancreas.
We report a case of homozygous DNAJC3 mutation in two siblings of a consanguineous family. A 3-year-old boy presented with short stature and a thyroid nodule. Laboratory findings confirmed hypothyroidism. Subsequently, levothyroxine was administered. Growth hormone (GH) stimulation test results were within the normal limits. His stature was exceedingly short (80.5 cm) (-3.79 SDS). The patient developed sensorineural hearing loss at age 6 years; his intellectual functioning was impaired. Recombinant Human Growth Hormine (rhGH) treatment was postponed until the age of 6.9 years due to a strong family history of diabetes. At age 9 years, he developed an ataxic gait. Brain magnetic resonance imaging (MRI) revealed neurodegeneration. The patient developed diabetes at the age of 11 years-5 years after the initiation of rhGH treatment. Tests for markers of autoimmune diabetes were negative. Lifestyle modification was introduced, but insulin therapy was eventually required. Whole-exome-sequencing (WES) revealed a homozygous DNAJC3 mutation, which explained his clinical presentation. MRI revealed a small, atrophic pancreas. At the age of 17, his final adult height was 143 cm (-4.7 SDS). His elder brother, who had the same mutation, had a similar history, except that he had milder ataxia and normal brain MRI finding at the age of 28 years.
We propose that DNAJC3 mutation can be considered as a cause of maturity onset diabetes of the young. Patients with DNAJC3 mutations may possess a small atrophic pancreas.
摘要：
■DNAJC3，在胰腺细胞中含量丰富，减弱内质网应激。据报道，纯合DNAJC3突变会导致非免疫性青少年糖尿病，神经变性,听力损失,身材矮小,和甲状腺功能减退。
■我们报告了一个近亲家族的两个兄弟姐妹中的纯合DNAJC3突变病例。一个3岁男孩，身材矮小，甲状腺结节。实验室检查结果证实甲状腺功能减退。随后，给予左甲状腺素。生长激素（GH）刺激测试结果在正常范围内。他的身材非常矮（80.5厘米）（-3.79SDS）。患者在6岁时出现感觉神经性听力损失；他的智力功能受损。重组人生长激素（rhGH）治疗由于糖尿病家族史而推迟至6.9岁。9岁时,他出现了共济失调步态.脑磁共振成像（MRI）显示神经变性。患者在开始rhGH治疗后11岁-5岁时发展为糖尿病。自身免疫性糖尿病标志物的检测为阴性。引入了生活方式的修改，但最终需要胰岛素治疗。全外显子组测序（WES）揭示了一个纯合的DNAJC3突变，解释了他的临床表现.核磁共振显示，萎缩性胰腺.17岁时，他的最终成年身高为143厘米（-4.7SDS）。他的哥哥，有相同突变的人，有类似的历史，除了他在28岁时有较轻的共济失调和正常的脑MRI发现。
■我们建议DNAJC3突变可以被认为是年轻人成年糖尿病的原因。具有DNAJC3突变的患者可能具有小的萎缩性胰腺。
■我们报告了一个近亲家族的两个兄弟姐妹中的纯合DNAJC3突变病例。一个3岁男孩，身材矮小，甲状腺结节。实验室检查结果证实甲状腺功能减退。随后，给予左甲状腺素。生长激素（GH）刺激测试结果在正常范围内。他的身材非常矮（80.5厘米）（-3.79SDS）。患者在6岁时出现感觉神经性听力损失；他的智力功能受损。重组人生长激素（rhGH）治疗由于糖尿病家族史而推迟至6.9岁。9岁时,他出现了共济失调步态.脑磁共振成像（MRI）显示神经变性。患者在开始rhGH治疗后11岁-5岁时发展为糖尿病。自身免疫性糖尿病标志物的检测为阴性。引入了生活方式的修改，但最终需要胰岛素治疗。全外显子组测序（WES）揭示了一个纯合的DNAJC3突变，解释了他的临床表现.核磁共振显示，萎缩性胰腺.17岁时，他的最终成年身高为143厘米（-4.7SDS）。他的哥哥，有相同突变的人，有类似的历史，除了他在28岁时有较轻的共济失调和正常的脑MRI发现。
■我们建议DNAJC3突变可以被认为是年轻人成年糖尿病的原因。具有DNAJC3突变的患者可能具有小的萎缩性胰腺。
