A homozygous stop gain mutation in BOD1 gene in a Lebanese patient with syndromic intellectual disability

• Published in: Clinical genetics Vol. 98; no. 3; pp. 288 - 292
• Main Authors: Hamdan, Nadine, Mehawej, Cybel, Sebaaly, Ghada, Jalkh, Nadine, Corbani, Sandra, Abou‐Ghoch, Joelle, De Backer, O., Chouery, Eliane
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2020
• Subjects: Cell division; Cell survival; Chromosomes; Cognitive ability; consanguinity; Genetic diversity; gonadal dysfunction; Hearing loss; Intellectual disabilities; Mutation; Neurodevelopmental disorders; Nonsense mutation; syndromic intellectual disability; whole exome sequencing; consanguinity; syndromic intellectual disability; gonadal dysfunction; whole exome sequencing
• DOI: 10.1111/cge.13799
• ISSN: 0009-9163

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. Whole Exome Sequencing led to the identification of BOD1 stop gain mutation (NM_138369: c.451C>T; p.R151*) in a Lebanese patient with syndromic intellectual disability, including: moderate mental disability (IQ of 44); endocrine dysfunction; and high‐frequency hearing impairment.