KIF26A is mutated in the syndrome of congenital hydrocephalus with megacolon.

Autor: Almannai M; Genetics and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia. almannaimo@mngha.med.sa.; Medical Genomics Research Department, King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia. almannaimo@mngha.med.sa.; College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. almannaimo@mngha.med.sa., AlAbdi L; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Department of Zoology, Collage of Science, King Saud University, Riyadh, Saudi Arabia., Maddirevula S; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Alotaibi M; Department of Genetics, King Saud Medical City, Riyadh, Saudi Arabia., Alsaleem BM; Gastroenterology Division, Intestinal Failure Rehabilitation Program, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia., Aljadhai YI; Department of Neuroimaging and Intervention, Medical Imaging Administration, King Fahad Medical City, Riyadh, Saudi Arabia., Alsaif HS; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Centre of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Abukhalid M; Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia., Alkuraya FS; Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. falkuraya@kfshrc.edu.sa.
Jazyk: angličtina
Zdroj: Human genetics [Hum Genet] 2023 Mar; Vol. 142 (3), pp. 399-405. Date of Electronic Publication: 2022 Dec 23.
DOI: 10.1007/s00439-022-02513-1
Abstrakt: Human disorders of the enteric nervous system (ENS), e.g., Hirschsprung's disease, are rarely associated with major central nervous system involvement. We describe two families each segregating a different homozygous truncating variant in KIF26A with a unique constellation of severe megacolon that resembles Hirschsprung's disease but lacks aganglionosis as well as brain malformations that range from severe to mild. The intestinal phenotype bears a striking resemblance to that observed in Kif26a -/- mice where KIF26A deficiency was found to cause abnormal GDNF-Ret signaling resulting in failure to establish normal neuronal networks despite myenteric neuronal hyperplasia. Very recently, a range of brain developmental phenotypes were described in patients and mice with KIF26A deficiency and were found to result from abnormal radial migration and increased apoptosis. Our report, therefore, reveals a recognizable autosomal-recessive human KIF26A deficiency phenotype characterized by severe ENS dysfunction and a range of brain malformations.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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