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

Alshammari, Muneera J.; Shamseldin, Hanan E.; Essbaiheen, Fahad; Eltahir, Sara H.; Alruwaili, Ashwag R.; Abdulwahab, Firdous; Alkuraya, Fowzan S.

doi:10.1007/s00439-023-02621-6

Hum. Genet.

2024

DOI: 10.1007/s00439-023-02621-6

|View full text |Cite

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

Muneera J. Alshammari,

Hanan E. Shamseldin,

Fahad Essbaiheen

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article2

Relationship

Self Cite0

Independent2

Authors

Journals

Cited by 2 publications

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Novel homozygous ESAM variants in two families with perinatal strokes showing variable neuroradiologic and clinical findings

Abdel-Salam,

Esmail,

Nagy

et al. 2024

J Hum Genet

View full text Add to dashboard Cite

Biallelic loss of function variants in ESAM (endothelial cell adhesion molecule) have recently been reported in 14 individuals (9 families) presenting with prenatal intracranial hemorrhage. Here, we describe four patients from two unrelated families in whom three of them presented with variable onset encephalopathy and seizures while one only displayed profound delay without seizures. Brain MRI showed variable onset intracranial hemorrhage that evolved to hydrocephalus in 3 patients, whereas hemosiderin deposits, white matter volume loss, and porencephalic cysts were noted in one patient. Unlike the majority of described cases, the youngest brother of the first family did not show microcephaly and failure to thrive. Exome sequencing identified two novel homozygous ESAM variants. A splice variant (c.731-2A>G) was identified in one family which was confirmed by investigating the patient’s mRNA to result in exon skipping and early protein truncation. In addition, a missense variant (c.561G>C; p.Trp187Cys) was identified in the other family, which is the first disease causing missense variant to be described in patients with ESAM deficient phenotype. In addition, a maternally inherited pathogenic MC4R variant (c.811T>C; p.Cys271 Arg) was also identified in the youngest brother of the first family. Variants in the MC4R gene are associated with a non-syndromic form of obesity that could explain the unusual macrocephaly and obesity. Our work establishes ESAM as a tight junction gene that can present with variable neuroradiological and clinical phenotypes when mutated. Moreover, it refines the phenotype of this ultrarare syndrome and extends the number and type of variants described to date.

show abstract

Novel homozygous ESAM variants in two families with perinatal strokes showing variable neuroradiologic and clinical findings

Abdel-Salam,

Esmail,

Nagy

et al. 2024

J Hum Genet

View full text Add to dashboard Cite

show abstract

Spotlight on Hemorrhagic Destruction of the Brain, Subependymal Calcification, and Congenital Cataracts (HDBSCC)

Kozak,

Mochida,

Lin

et al. 2024

View full text Add to dashboard Cite

Hemorrhagic Destruction of the Brain, Subependymal Calcification, and Congenital Cataracts (HDBSCC) is a rare syndrome caused by biallelic mutations in the JAM3 gene with significant intrafamilial variability in clinical presentation and brain imaging phenotypes. The clinical presentation of HDBSCC includes severe recurrent hemorrhages involving the brain parenchyma and the ventricles beginning in utero and continuing in infancy together with dense central cataracts present at birth. This comprehensive review documents reported cases on this unique condition and describes its genetic, neuroradiologic and ophthalmic features. It should be included in the differential diagnosis of children with congenital cataracts and neurodevelopmental abnormalities. Unique clinical, imaging findings and genetic testing can help the diagnosis.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

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

Cited by 2 publications

References 27 publications

Novel homozygous ESAM variants in two families with perinatal strokes showing variable neuroradiologic and clinical findings

Novel homozygous ESAM variants in two families with perinatal strokes showing variable neuroradiologic and clinical findings

Spotlight on Hemorrhagic Destruction of the Brain, Subependymal Calcification, and Congenital Cataracts (HDBSCC)

Contact Info

Product

Resources

About