PDF(Pubmed)
Abstract：
Peptidyl-tRNA hydrolase 2 (PTRH2) is an evolutionarily highly conserved mitochondrial protein. The biallelic mutations in the PTRH2 gene have been suggested to cause a rare autosomal recessive disorder characterized by an infantile-onset multisystem neurologic endocrine and pancreatic disease (IMNEPD). Patients with IMNEPD present varying clinical manifestations, including global developmental delay associated with microcephaly, growth retardation, progressive ataxia, distal muscle weakness with ankle contractures, demyelinating sensorimotor neuropathy, sensorineural hearing loss, and abnormalities of thyroid, pancreas, and liver. In the current study, we conducted an extensive literature review with an emphasis on the variable clinical spectrum and genotypes in patients. Additionally, we reported on a new case with a previously documented mutation. A bioinformatics analysis of the various PTRH2 gene variants was also carried out from a structural perspective. It appears that the most common clinical characteristics among all patients include motor delay (92%), neuropathy (90%), distal weakness (86.4%), intellectual disability (84%), hearing impairment (80%), ataxia (79%), and deformity of head and face (~70%). The less common characteristics include hand deformity (64%), cerebellar atrophy/hypoplasia (47%), and pancreatic abnormality (35%), while the least common appear to be diabetes mellitus (~30%), liver abnormality (~22%), and hypothyroidism (16%). Three missense mutations were revealed in the PTRH2 gene, the most common one being Q85P, which was shared by four different Arab communities and was presented in our new case. Moreover, four different nonsense mutations in the PTRH2 gene were detected. It may be concluded that disease severity depends on the PTRH2 gene variant, as most of the clinical features are manifested by nonsense mutations, while only the common features are presented by missense mutations. A bioinformatics analysis of the various PTRH2 gene variants also suggested the mutations to be deleterious, as they seem to disrupt the structural confirmation of the enzyme, leading to loss of stability and functionality.
摘要：
肽基tRNA水解酶2(PTRH2)是一种进化上高度保守的线粒体蛋白。PTRH2基因的双等位基因突变已被认为会导致罕见的常染色体隐性遗传疾病，其特征是婴儿发作的多系统神经内分泌和胰腺疾病（IMNEPD）。IMNEPD患者表现出不同的临床表现，包括与小头畸形相关的全球发育迟缓，生长迟缓,进行性共济失调,远端肌肉无力伴踝关节挛缩，脱髓鞘性感觉运动神经病,感觉神经性听力损失,甲状腺异常，胰腺,还有肝脏.在目前的研究中,我们进行了广泛的文献综述,重点是患者的可变临床谱和基因型.此外,我们报道了一个先前记录的突变的新病例。还从结构角度对各种PTRH2基因变体进行了生物信息学分析。似乎所有患者中最常见的临床特征包括运动延迟（92％），神经病变（90%），远端无力（86.4%），智力残疾（84%），听力障碍（80%），共济失调（79%），头部和面部畸形（约70％）。较不常见的特征包括手畸形（64％），小脑萎缩/发育不全（47%），胰腺异常（35%），虽然最不常见的似乎是糖尿病（约30％），肝脏异常（~22%），和甲状腺功能减退（16％）。在PTRH2基因中发现了三个错义突变，最常见的是Q85P，它由四个不同的阿拉伯社区共享，并在我们的新案例中呈现。此外，在PTRH2基因中检测到四种不同的无义突变。可以得出结论，疾病的严重程度取决于PTRH2基因变异，因为大多数临床特征都表现为无义突变，而错义突变仅呈现共同特征。对各种PTRH2基因变体的生物信息学分析也表明突变是有害的，因为它们似乎破坏了酶的结构确认，导致丧失稳定性和功能性。
