CEP104 and CEP290 ; Genes with Ciliary Functions Cause Intellectual Disability in Multiple Families.

Autor: Khoshbakht S; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Beheshtian M; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.; Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran., Fattahi Z; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.; Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran., Bazazzadegan N; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Parsimehr E; Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran., Fadaee M; Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran., Vazehan R; Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran., Faraji Zonooz M; Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran., Abolhassani A; Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran., Makvand M; Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran., Kariminejad A; Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran., Celik A; Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey., Kahrizi K; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Najmabadi H; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.; Kariminejad - Najmabadi Pathology & Genetics Center, Tehran, Iran.
Jazyk: angličtina
Zdroj: Archives of Iranian medicine [Arch Iran Med] 2021 May 01; Vol. 24 (5), pp. 364-373. Date of Electronic Publication: 2021 May 01.
DOI: 10.34172/aim.2021.53
Abstrakt: Background: Neurodevelopmental and intellectual impairments are extremely heterogeneous disorders caused by a diverse variety of genes involved in different molecular pathways and networks. Genetic alterations in cilia, highly-conserved organelles with sensorineural and signal transduction roles can compromise their proper functions and lead to so-called "ciliopathies" featuring intellectual disability (ID) or neurodevelopmental disorders as frequent clinical manifestations. Here, we report several Iranian families affected with ID and other ciliopathy-associated features carrying known and novel variants in two ciliary genes; CEP104 and CEP290 .
Methods: Whole exome and Targeted exome sequencing were carried out on affected individuals. Lymphoblastoid cell lines (LCLs) derived from the members of affected families were established for two families carrying CEP104 mutations. RNA and protein expression studies were carried out on these cells using qPCR and Western blot, respectively.
Results: A novel homozygous variant; NM_025114.3:c.7341_7344dupACTT p.(Ser2449Thrfs*8) and four previously reported homozygous variants; NM_025114.3:c.322C>T p.(Arg108*), NM_025114.3:c.4393C>T p.(Arg1465*), NM_025114.3:c.5668G>T p.(Gly1890*) and NM_025114.3:c.1666dupA p.(Ile556Asnfs*20) were identified in CEP290 . In two other families, two novel homozygous variants; NM_014704:c.2356_2357insTT p.(Cys786Phefs*11) and NM_014704:c.1901_1902insT p.(Leu634Phefs*33) were identified in CEP104 , another ciliary gene. qPCR and Western blot analyses showed significantly lower levels of CEP104 transcripts and protein in patients compared to heterozygous or normal family members.
Conclusion: We emphasize on the clinical variability and pleiotropic phenotypes due to variants of these genes. In conclusion, our findings support the pivotal role of these genes resulting in cognitive and neurodevelopmental features.
(© 2021 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)
Databáze: MEDLINE
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