Targeted re-sequencing in pediatric and perinatal stroke

Grossi, Alice; Severino, Mariasavina; Rusmini, Marta; Tortora, Domenico; Ramenghi, Luca A.; Cama, Armando; Rossi, Andrea; Rocco, Maja Di; Ceccherini, Isabella; Bertamino, Marta; Amico, Giulia; Banov, Laura; Capra, Valérie; Caorsi, Roberta; Caroli, Fabrizio; Giacomini, Thea; Ac, Molinari; Moretti, Paolo; Moscatelli, Andrea; Nobili, Lucia; Palmieri, Antonella; Pavanello, Marco; Prato, Giulia; Alessandro, Riccardo; Ronchetti, Anna; Signa, Sara; Uccella, Sarà

doi:10.1016/j.ejmg.2020.104030

Cited by 14 publications

(8 citation statements)

References 39 publications

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“…COL4A1 causes several autosomal dominant syndromes that have been associated with stroke[6]. Patient 96169 was an adult male with developmental delay, hypotonia, seizures, dysmorphic facies, cataracts and brainstem strokes.…”

Section: Resultsmentioning

confidence: 99%

“…Including these additional cases, the only recurrent genes were COL4A1 and ATP13A2. COL4A1 causes several autosomal dominant syndromes that have been associated with stroke [6].…”

Section: Recurrent Genes Observed In the Cohortmentioning

confidence: 99%

“…Monogenic causes of stroke include CADASIL, homocystinuria, Fabry disease, TREX1, COL4A1/COL4A2-related syndromes, and others [4,5]. One study of 38 patients with pediatric and perinatal stroke diagnosed 10% of cases using a panel of 15 genes focused on Mendelian causes of stroke [6]. Others have similarly shown the importance of gene-panel testing in evaluation of stroke [7].…”

Section: Introductionmentioning

confidence: 99%

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Clinical exome sequencing for stroke evaluation uncovers a high frequency of Mendelian disorders: a retrospective analysis

Kumar

Meng

Liu

et al. 2022

Preprint

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BackgroundStroke causes significant disability and is a common cause of death worldwide. Previous studies have estimated that 1-5% of stroke is attributable to monogenic etiologies. We set out to assess the utility of clinical exome sequencing (ES) in the evaluation of stroke.MethodsWe retrospectively analyzed 124 individuals who received ES at the Baylor Genetics reference lab between 2012 and 2021 who had stroke as a major part of their reported phenotype.ResultsAges ranged from 10 days to 69 years. 8.9% of the cohort received a diagnosis, including 25% of infants less than 1 year old; an additional 10.5% of the cohort received a probable diagnosis. We identified several syndromes that predispose to stroke such as COL4A1-related brain small vessel disease, CBS-related homocystinuria, POLG-related disorders, TTC19-related mitochondrial disease, and RNASEH2A associated Aicardi-Goutieres syndrome. We also observed pathogenic variants in NSD1, PKHD1, HRAS and ATP13A2, which are genes rarely associated with stroke.ConclusionsAlthough stroke is a complex phenotype with varying pathologies and risk factors, these results show that use of exome sequencing can be highly relevant in stroke, especially for those presenting <1 year of age.

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Section: Resultsmentioning

confidence: 99%

“…Including these additional cases, the only recurrent genes were COL4A1 and ATP13A2. COL4A1 causes several autosomal dominant syndromes that have been associated with stroke [6].…”

Section: Recurrent Genes Observed In the Cohortmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical exome sequencing for stroke evaluation uncovers a high frequency of Mendelian disorders: a retrospective analysis

Kumar

Meng

Liu

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…COL4A1 causes several autosomal dominant syndromes that have been associated with stroke (Grossi et al, 2020). Patient 96169 was an adult male with developmental delay, hypotonia, seizures, dysmorphic facies, cataracts, and brainstem strokes.…”

Section: Recurrent Genes Observed In the Cohortmentioning

confidence: 99%

Clinical exome sequencing uncovers a high frequency of Mendelian disorders in infants with stroke: A retrospective analysis

Kumar

Meng

Liu

et al. 2022

American J of Med Genetics Pt A

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Stroke causes significant disability and is a common cause of death worldwide. Previous studies have estimated that 1%-5% of stroke is attributable to monogenic etiologies. We set out to assess the utility of clinical exome sequencing (ES) in the evaluation of stroke. We retrospectively analyzed 124 individuals who received ES at the Baylor Genetics reference lab between 2012 and 2021 who had stroke as a major part of their reported phenotype. Ages ranged from 10 days to 69 years. 8.9% of the cohort received a diagnosis, including 25% of infants less than 1 year old; an additional 10.5% of the cohort received a probable diagnosis. We identified several syndromes that predispose to stroke such as COL4A1-related brain small vessel disease, homocystinuria caused by CBS mutation, POLG-related disorders, TTC19-linked mitochondrial disease, and RNASEH2A associated Aicardi-Goutieres syndrome. We also observed pathogenic variants in NSD1, PKHD1, HRAS, and ATP13A2, which are genes rarely associated with stroke. Although stroke is a complex phenotype with varying pathologies and risk factors, these results show that use of exome sequencing can be highly relevant in stroke, especially for those presenting <1 year of age.

show abstract

“…Pathogenetic variants associated with susceptibility to brain VZV infections in the RNA Polymerase III subunit C (POLR3C), A (POLR3A) and F (POLR3F) genes were ruled out (22)(23)(24)(25) via targeted Next Generation Sequencing panel and Sanger Sequencing. Finally, a NGS panel including 15 genes was performed to exclude the more frequent monogenetic causes of stroke in children (26,27). In particular, considered the involvement of posterior circulation at clinical onset, pathogenic variants in the ADA2 gene, encoding the adenosine deaminase 2 and responsible for a multisystem disease associated with early onset recurrent lacunar strokes, were excluded (28).…”

Section: Case Presentationmentioning

confidence: 99%

An atypical case of post-varicella stroke in a child presenting with hemichorea followed by late-onset inflammatory focal cerebral arteriopathy

Bertamino

Signa

Vagelli

et al. 2021

Quant Imaging Med Surg

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Targeted re-sequencing in pediatric and perinatal stroke

Cited by 14 publications

References 39 publications

Clinical exome sequencing for stroke evaluation uncovers a high frequency of Mendelian disorders: a retrospective analysis

Clinical exome sequencing for stroke evaluation uncovers a high frequency of Mendelian disorders: a retrospective analysis

Clinical exome sequencing uncovers a high frequency of Mendelian disorders in infants with stroke: A retrospective analysis

An atypical case of post-varicella stroke in a child presenting with hemichorea followed by late-onset inflammatory focal cerebral arteriopathy

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