Genomic analysis of presumed perinatal stroke in Saudi Arabia reveals a strong monogenic contribution

Genomic analysis of presumed perinatal stroke in Saudi Arabia reveals a strong monogenic contribution

Perinatal stroke is associated with significant short- and long-term morbidity and has been recognized as the most common cause of cerebral palsy in term infants. The diagnosis of presumed perinatal stroke (PPS) is made in children who present with neurological deficit and/or seizures attributable t...

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Bibliographic Details
Published in:Human genetics Vol. 143; no. 1; pp. 59 - 69
Main Authors: Alshammari, Muneera J., Shamseldin, Hanan E., Essbaiheen, Fahad, Eltahir, Sara H., Alruwaili, Ashwag R., Abdulwahab, Firdous, Alkuraya, Fowzan S.
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 2024
Springer Nature B.V
Subjects:
Biomedical and Life Sciences
Biomedicine
Cerebral infarction
Developmental disabilities
Gene Function
Genomic analysis
Human Genetics
Metabolic Diseases
Molecular Medicine
Morbidity
Neonates
Neuroimaging
Original Investigation
Risk factors
Seizures
Stroke
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Summary:Perinatal stroke is associated with significant short- and long-term morbidity and has been recognized as the most common cause of cerebral palsy in term infants. The diagnosis of presumed perinatal stroke (PPS) is made in children who present with neurological deficit and/or seizures attributable to focal chronic infarction on neuroimaging and have uneventful neonatal history. The underlying mechanism of presumed perinatal stroke remains unknown and thorough investigation of potential monogenic causes has not been conducted to date. Here, we describe the use of untargeted exome sequencing to investigate a cohort of eight patients from six families with PPS. A likely deleterious variant was identified in four families. These include the well-established risk genes COL4A2 and JAM3 . In addition, we report the first independent confirmation of the recently described link between ESAM and perinatal stroke. Our data also highlight NID1 as a candidate gene for the condition. This study suggests that monogenic disorders are important contributors to the pathogenesis of PPS and should be investigated by untargeted sequencing especially when traditional risk factors are excluded.
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ISSN:0340-6717
1432-1203
DOI:10.1007/s00439-023-02621-6