Intellectual disability (ID), occurring in syndromic or non-syndromic forms, is the most common neurodevelopmental disorder. Although many cases are caused by single gene defects, ID is highly genetically heterogeneous. Biallelic variants in the transmembrane protein TMEM147 have recently been linked to intellectual disability with dysmorphic facial features. TMEM147 is believed to localize to the endoplasmic reticulum membrane and nuclear envelope and also involved in biogenesis of multi-pass membrane proteins. Here, we report two patients born to a consanguineous family with a novel loss-of-function variant; (NM_001242597.2:c.193-197del) in TMEM147 causing intellectual disability and spasticity. Whole exome sequencing and validating Sanger sequencing were utilized to confirm the identified causal variant. Our findings were in line with the previously described patients with TMEM147 variants manifesting intellectual disability as a major clinical sign but also featured spasticity as a phenotypic expansion. This study provides additional evidence for the pathogenicity of TMEM147 mutations in intellectual disability and expands the phenotypic and variant spectrum linked to this gene.

智力障碍（ID）以综合征或非综合征形式发生，是最常见的神经发育障碍。尽管许多病例是由单基因缺陷引起的，但 ID 具有高度的遗传异质性。最近，跨膜蛋白TMEM147的双等位基因变异与面部特征畸形的智力障碍有关。据信TMEM147定位于内质网膜和核膜，并且还参与多通道膜蛋白的生物发生。在这里，我们报告了两名出生于近亲家庭的患者，患有一种新型功能丧失变异；(NM_001242597.2:c.193-197del) 存在于TMEM147中，导致智力障碍和痉挛。利用全外显子组测序和验证桑格测序来确认已识别的因果变异。我们的研究结果与之前描述的TMEM147变异患者一致，这些患者表现为智力障碍作为主要临床症状，但也以痉挛为表型扩展。这项研究为TMEM147突变对智力障碍的致病性提供了额外的证据，并扩展了与该基因相关的表型和变异谱。