BACKGROUND Primary microcephaly is defined as reduced occipital-frontal circumference noticeable before 36 weeks of gestation. Large amount of insults might lead to microcephaly including infections, hypoxia and genetic mutations. More than 16 genes are described in autosomal recessive primary microcephaly. However, the cause of microcephaly remains unclear in many cases after extensive investigations and genetic screening. CASE PRESENTATION Here, we described the case of a boy with primary microcephaly who presented to a neurology clinic with short stature, global development delay, dyskinetic movement, strabismus and dysmorphic features. We performed microcephaly investigations and genetic panels. Then, we performed whole-exome sequencing to identify any genetic cause. Microcephaly investigations and genetic panels were negative, but we found a new D317V homozygous mutation in TELOE-2 interacting protein 2 (TTI2) gene by whole-exome sequencing. TTI2 is implicated in DNA damage response and mutation in that gene was previously described in mental retardation, autosomal recessive 39. CONCLUSIONS We described the first French Canadian case with primary microcephaly and global developmental delay secondary to a new D317V homozygous mutation in TTI2 gene. Our report also highlights the importance of TTI2 protein in brain development.

中文翻译：

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全外显子测序可确定一名原发性小头畸形儿童的TTI2纯合突变：一例病例报告。

背景技术原发性小头畸形被定义为在妊娠36周之前可观察到的枕前额周长减少。大量侮辱可能导致小头畸形，包括感染，缺氧和基因突变。常染色体隐性原发性小头畸形中描述了超过16个基因。但是，经过广泛的研究和基因筛选后，在许多情况下小头畸形的病因仍不清楚。病例介绍在这里，我们描述了一个原发性小头畸形男孩的病例，该男孩身高矮小，整体发育迟缓，运动障碍，斜视和畸形特征出现在神经内科诊所。我们进行了小头畸形调查和遗传学调查。然后，我们进行了全外显子测序，以确定任何遗传原因。小头畸形检查和遗传检查均阴性，但是我们通过全外显子组测序发现了TELOE-2相互作用蛋白2（TTI2）基因中的一个新的D317V纯合突变。TTI2与DNA损伤反应有关，而该基因的突变先前曾描述为智力低下，常染色体隐性遗传39。结论我们描述了第一例加拿大法语病例，该病原发于小头畸形，继发于TTI2基因新的D317V纯合突变而导致全球发育延迟。我们的报告还强调了TTI2蛋白在大脑发育中的重要性。结论我们描述了第一例加拿大法语病例，其原发性小头畸形和整体发育延迟继发于TTI2基因新的D317V纯合突变。我们的报告还强调了TTI2蛋白在大脑发育中的重要性。结论我们描述了第一例加拿大法语病例，其原发性小头畸形和整体发育延迟继发于TTI2基因新的D317V纯合突变。我们的报告还强调了TTI2蛋白在大脑发育中的重要性。