Sharkia Rajech, Shalev Stavit A, Zalan Abdelnaser, Marom-David Milit, Watemberg Nathan, Urquhart Jill E, Daly Sarah B, Bhaskar Sanjeev S, Williams Simon G, Newman William G, Spiegel Ronen, Azem Abdussalam, Elpeleg Orly, Mahajnah Muhammad
The Triangle Regional Research and Development Center, Kfar Qari', Israel.
Beit-Berl Academic College, Beit-Berl, Israel.
Am J Med Genet A. 2017 Apr;173(4):1051-1055. doi: 10.1002/ajmg.a.38140.
PTRH2 is an evolutionarily highly conserved mitochondrial protein that belongs to a family of peptidyl-tRNA hydrolases. Recently, patients from two consanguineous families with mutations in the PTRH2 gene were reported. Global developmental delay associated with microcephaly, growth retardation, progressive ataxia, distal muscle weakness with ankle contractures, demyelinating sensorimotor neuropathy, and sensorineural hearing loss were present in all patients, while facial dysmorphism with widely spaced eyes, exotropia, thin upper lip, proximally placed thumbs, and deformities of the fingers and toes were present in some individuals. Here, we report a new family with three siblings affected by sensorineural hearing loss and peripheral neuropathy. Autozygosity mapping followed by exome sequencing identified a previously reported homozygous missense mutation in PTRH2 (c.254A>C; p.(Gln85Pro)). Sanger sequencing confirmed that the variant segregated with the phenotype. In contrast to the previously reported patient, the affected siblings had normal intelligence, milder microcephaly, delayed puberty, myopia, and moderate insensitivity to pain. Our findings expand the clinical phenotype and further demonstrate the clinical heterogeneity related to PTRH2 variants.
PTRH2是一种在进化上高度保守的线粒体蛋白,属于肽基-tRNA水解酶家族。最近,有报道称来自两个近亲家庭的患者存在PTRH2基因突变。所有患者均出现与小头畸形相关的全球发育迟缓、生长发育迟缓、进行性共济失调、伴有踝关节挛缩的远端肌肉无力、脱髓鞘感觉运动神经病和感音神经性听力损失,而部分个体存在面部畸形,表现为眼距宽、外斜视、上唇薄、拇指位置近以及手指和脚趾畸形。在此,我们报告一个新的家庭,有三个兄弟姐妹患有感音神经性听力损失和周围神经病。通过纯合性定位随后进行外显子组测序,在PTRH2基因中鉴定出一个先前报道的纯合错义突变(c.254A>C;p.(Gln85Pro))。Sanger测序证实该变异与表型共分离。与先前报道的患者不同,受影响的兄弟姐妹智力正常,小头畸形较轻,青春期延迟,近视,对疼痛中度不敏感。我们的研究结果扩展了临床表型,并进一步证明了与PTRH2变异相关的临床异质性。