A biallelic loss-of-function variant in TMEM147 causes profound intellectual disability and spasticity.
A biallelic loss-of-function variant in TMEM147 causes profound intellectual disability and spasticity.
复制标题
TMEM147 中的双等位基因功能丧失变异会导致严重的智力障碍和痉挛。
DOI：
10.1007/s10048-023-00734-8
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发表时间：
2023
期刊：
影响因子：
2.2
通讯作者：
Mozdarani,Hossein
中科院分区：
文献类型：
--
作者：
Ghorashi,Tahereh;Darvish,Hossein;Bakhtiari,Somayeh;Tafakhori,Abbas;Kruer,MichaelC;Mozdarani,Hossein
智力残疾（ID），发生在综合征或非综合征的形式，是最常见的神经发育障碍。虽然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。跨膜蛋白TMEM 147的双等位基因变异与面部畸形的智力残疾有关，TMEM 147定位于内质网膜和核膜，并参与多通道膜蛋白的生物合成。在这里，我们报告了两名患者出生于一个近亲家庭，一个新的功能丧失的变异;（NM_001242597.2：c.193- 197 del）inTMEM 147造成智力残疾和痉挛。利用全外显子组测序和验证桑格测序来确认鉴定的致病变体。我们的研究结果与先前描述的TMEM 147变异患者一致，这些患者表现为智力残疾作为主要临床体征，但也表现为痉挛作为表型扩展。这项研究为TMEM 147突变在智力残疾中的致病性提供了额外的证据，并扩大了与该基因相关的表型和变异谱。
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 proteinTMEM147have recently been linked to intellectual disability with dysmorphic facial features.TMEM147is 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) inTMEM147causing 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 withTMEM147variants manifesting intellectual disability as a major clinical sign but also featured spasticity as a phenotypic expansion. This study provides additional evidence for the pathogenicity ofTMEM147mutations in intellectual disability and expands the phenotypic and variant spectrum linked to this gene.