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Duan Y, Lin S, Xie L, et al. Exome sequencing identifies a novel mutation of the GDI1 gene in a Chinese non-syndromic X-linked intellectual disability family. Genet Mol Biol. 2017;40(3):591-596doi: 10.1590/1678-4685-GMB-2016-0249.
Duan, Y., Lin, S., Xie, L., Zheng, K., Chen, S., Song, H., Zeng, X., Gu, X., Wang, H., Zhang, L., Shao, H., Hong, W., Zhang, L., & Duan, S. (2017). Exome sequencing identifies a novel mutation of the GDI1 gene in a Chinese non-syndromic X-linked intellectual disability family. Genetics and molecular biology, 40(3), 591-596. https://doi.org/10.1590/1678-4685-GMB-2016-0249
Duan, Yongheng, et al. "Exome sequencing identifies a novel mutation of the GDI1 gene in a Chinese non-syndromic X-linked intellectual disability family." Genetics and molecular biology vol. 40,3 (2017): 591-596. doi: https://doi.org/10.1590/1678-4685-GMB-2016-0249
Duan Y, Lin S, Xie L, Zheng K, Chen S, Song H, Zeng X, Gu X, Wang H, Zhang L, Shao H, Hong W, Zhang L, Duan S. Exome sequencing identifies a novel mutation of the GDI1 gene in a Chinese non-syndromic X-linked intellectual disability family. Genet Mol Biol. 2017 Jul-Sep;40(3):591-596. doi: 10.1590/1678-4685-GMB-2016-0249. Epub 2017 Aug 31. PMID: 28863211; PMCID: PMC5596370.
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Genet Mol Biol. 2017 Jul-Sep;40(3):591-596. doi: 10.1590/1678-4685-GMB-2016-0249. Epub 2017 Aug 31.

Exome sequencing identifies a novel mutation of the GDI1 gene in a Chinese non-syndromic X-linked intellectual disability family.

Genetics and molecular biology

Yongheng Duan, Sheng Lin, Lichun Xie, Kaifeng Zheng, Shiguo Chen, Hui Song, Xuchun Zeng, Xueying Gu, Heyun Wang, Linghua Zhang, Hao Shao, Wenxu Hong, Lijie Zhang, Shan Duan

Affiliations

  1. Laboratory of Medical Genetics, Center for Birth Defect Research and Prevention, Shenzhen Research Institute of Population and Family Planning, Shenzhen City, People's Republic of China.
  2. College of Pharmacy, Nankai University, Tianjin City, People's Republic of China.

PMID: 28863211 PMCID: PMC5596370 DOI: 10.1590/1678-4685-GMB-2016-0249

Abstract

X-linked intellectual disability (XLID) has been associated with various genes. Diagnosis of XLID, especially for non-syndromic ones (NS-XLID), is often hampered by the heterogeneity of this disease. Here we report the case of a Chinese family in which three males suffer from intellectual disability (ID). The three patients shared the same phenotype: no typical clinical manifestation other than IQ score ≤ 70. For a genetic diagnosis for this family we carried out whole exome sequencing on the proband, and validated 16 variants of interest in the genomic DNA of all the family members. A missense mutation (c.710G > T), which mapped to exon 6 of the Rab GDP-Dissociation Inhibitor 1 (GDI1) gene, was found segregating with the ID phenotype, and this mutation changes the 237th position in the guanosine diphosphate dissociation inhibitor (GDI) protein from glycine to valine (p. Gly237Val). Through molecular dynamics simulations we found that this substitution results in a conformational change of GDI, possibly affecting the Rab-binding capacity of this protein. In conclusion, our study identified a novel GDI1 mutation that is possibly NS-XLID causative, and showed that whole exome sequencing provides advantages for detecting novel ID-associated variants and can greatly facilitate the genetic diagnosis of the disease.

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