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Truncating biallelic variant in DNAJA1, encoding the co-chaperone Hsp40, is associated with intellectual disability and seizures

  • Saud Alsahli
  • Ahmed Alfares
  • Francisco J. Guzmán-Vega
  • Stefan T. Arold
  • Duaa Ba-Armah
  • Fuad Al MutairiEmail author
Short Communication
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Abstract

Intellectual disability poses a huge burden on the health care system, and it is one of the most common referral reasons to the genetic and child neurology clinic. Intellectual disability (ID) is genetically heterogeneous, and it is associated with several other neurological conditions. Exome sequencing is a robust genetic tool and has revolutionized the process of molecular diagnosis and novel gene discovery. Besides its diagnostic clinical value, novel gene discovery is prime in reverse genetics, when human mutations help to understand the function of a gene and may aid in better understanding of the human brain and nervous system. Using WES, we identified a biallelic truncating variant in DNAJA1 gene (c.511C>T p.(Gln171*) in a multiplex Saudi consanguineous family. The main phenotype shared between the siblings was intellectual disability and seizure disorder.

Keywords

Intellectual disability Seizure disorder DNAJA1 Exome sequencing Chaperonopathy Chaperone Co-chaperone Hsp40 

Notes

Acknowledgments

We would thank the studied family for their enthusiastic participation.

Contributorship statement

SA and FA created the presented idea and wrote the manuscript. SA, DB, and FA contributed to the patient care and diagnosis. SA, AA, DB, and FA prepared the tables. SA, AA, STA, FJG, and FA prepared the figures. SA, AA, STA, FJG, DB, and FA edited the manuscript.

Funding information

The research by STA and FJGV reported in this publication was supported by funding from King Abdullah University of Science and Technology (KAUST) through the baseline fund and the Office of Sponsored Research (OSR), under award number FCC/1/1976-25-01.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10048_2019_573_MOESM1_ESM.docx (14 kb)
Table S1 Regions of homozygosity in the current cohort. (DOCX 14 kb)
10048_2019_573_MOESM2_ESM.docx (15 kb)
Table S2 Detailed clinical synopsis (DOCX 15 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Saud Alsahli
    • 1
    • 2
  • Ahmed Alfares
    • 3
    • 4
  • Francisco J. Guzmán-Vega
    • 5
  • Stefan T. Arold
    • 5
  • Duaa Ba-Armah
    • 2
    • 6
  • Fuad Al Mutairi
    • 2
    • 7
    Email author
  1. 1.Department of Pediatric NeurologyTexas Children’s Hospital, Baylor College of MedicineHoustonUSA
  2. 2.King Abdullah International Medical Research Center (KAIMRC), College of MedicineKing Saud bin Abdulaziz University for Health SciencesRiyadhSaudi Arabia
  3. 3.Department of Pathology and Laboratory Medicine, King Abdulaziz Medical CityMinistry of National Guard-Health Affairs (MNGHA)RiyadhSaudi Arabia
  4. 4.Department of PediatricsQassim UniversityBuraydahSaudi Arabia
  5. 5.Division of Biological and Environmental Sciences and Engineering (BESE)King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC)ThuwalSaudi Arabia
  6. 6.Department of Pediatrics, King Abdulaziz Medical City, Division of Pediatric NeurologyMinistry of National Guard-Health Affairs (MNGHA)RiyadhSaudi Arabia
  7. 7.Division of Genetics, Department of Pediatrics, King Abdulaziz Medical CityMinistry of National Guard-Health Affairs (MNGHA)RiyadhSaudi Arabia

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