Medical Genetics Unit, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
Endocrinology Department, Bellevue Medical Center, Mansourieh, Lebanon.
Clin Genet. 2020 Sep;98(3):288-292. doi: 10.1111/cge.13799.
Intellectual disability (ID) is a neurodevelopmental disorder characterized by limitations in both intellectual and behavioral functioning. It can occur in non-syndromic and syndromic forms involving multiple organs. While the majority of genetic variants linked to ID are de novo, inherited variants are also detected in some forms. Here, we report a consanguineous Lebanese family presenting with an autosomal recessive syndromic ID characterized by neurodevelopmental delay, mild dysmorphic features, hearing impairment and endocrine dysfunction. Whole exome sequencing enabled the detection of the homozygous nonsense mutation in BOD1, p.R151X, in the proband. BOD1 is required for chromosomes biorientation during cell division. It also contributes to the regulation of cell survival and to the modulation of fatty acid metabolism. Another nonsense mutation in BOD1 was linked to ID in a consanguineous Iranian family. This is the second report of BOD1 mutations in humans and the first in a syndromic ID including gonadal dysfunction and high-frequency hearing impairment. Our findings confirm the involvement of BOD1 in cognitive functioning and expand the clinical spectrum of BOD1 deficiency.
智力残疾(ID)是一种神经发育障碍,其特点是智力和行为功能都有限。它可以是非综合征性和综合征性的,涉及多个器官。虽然大多数与 ID 相关的遗传变异是新生的,但在某些形式中也检测到遗传变异。在这里,我们报告了一个有亲缘关系的黎巴嫩家族,该家族表现出自体隐性综合征性 ID,其特征是神经发育迟缓、轻度畸形特征、听力障碍和内分泌功能障碍。全外显子组测序在先证者中检测到 BOD1 基因的纯合无义突变,p.R151X。BOD1 在细胞分裂过程中对染色体的双定向是必需的。它还有助于细胞存活的调节和脂肪酸代谢的调节。BOD1 的另一个无义突变与一个有亲缘关系的伊朗家族的 ID 有关。这是 BOD1 突变在人类中的第二次报道,也是第一个包括性腺功能障碍和高频听力障碍的综合征性 ID 的报道。我们的研究结果证实了 BOD1 参与认知功能,并扩展了 BOD1 缺乏的临床谱。