Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects

Bukowska‐Olech, Ewelina; Sowińska‐Seidler, Anna; Larysz, Dawid; Gawliński, Paweł; Koczyk, Grzegorz; Popiel, Delfina; Gurba-Bryśkiewicz, Lidia; Materna‐Kiryluk, Anna; Adamek, Zuzanna; Szczepankiewicz, Aleksandra; Dominiak, Paweł; Glista, Filip; Matuszewska, Karolina; Jamsheer, Aleksander

doi:10.3389/fmolb.2022.865494

Cited by 4 publications

(3 citation statements)

References 56 publications

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“…Furthermore, WES and WGS enable targeted in silico analysis of a custom-designed CS-related gene panel and performance of a broader exome/genome analysis in cases returning negative results. This is a cost-effective strategy that increases the diagnostic yield and can be adapted to the phenotypic presentation ( Miller et al, 2017 ; Tønne et al, 2020 ; Hyder et al, 2021 ; Bukowska-Olech et al, 2022 ; Tønne et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The value of genome-wide analysis in craniosynostosis

Topa,

Rohlin,

Fehr

et al. 2024

Front. Genet.

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Background: This study assessed the diagnostic yield of high-throughput sequencing methods in a cohort of craniosynostosis (CS) patients not presenting causal variants identified through previous targeted analysis.Methods: Whole-genome or whole-exome sequencing (WGS/WES) was performed in a cohort of 59 patients (from 57 families) assessed by retrospective phenotyping as having syndromic or nonsyndromic CS.Results: A syndromic form was identified in 51% of the unrelated cases. A genetic cause was identified in 38% of syndromic cases, with novel variants detected in FGFR2 (a rare Alu insertion), TWIST1, TCF12, KIAA0586, HDAC9, FOXP1, and NSD2. Additionally, we report two patients with rare recurrent variants in KAT6A and YY1 as well as two patients with structural genomic aberrations: one with a 22q13 duplication and one with a complex rearrangement involving chromosome 2 (2p25 duplication including SOX11 and deletion of 2q22). Moreover, we identified potentially relevant variants in 87% of the remaining families with no previously detected causal variants, including novel variants in ADAMTSL4, ASH1L, ATRX, C2CD3, CHD5, ERF, H4C5, IFT122, IFT140, KDM6B, KMT2D, LTBP1, MAP3K7, NOTCH2, NSD1, SOS1, SPRY1, POLR2A, PRRX1, RECQL4, TAB2, TAOK1, TET3, TGFBR1, TCF20, and ZBTB20.Conclusion: These results confirm WGS/WES as a powerful diagnostic tool capable of either targeted in silico or broad genomic analysis depending on phenotypic presentation (e.g., classical or unusual forms of syndromic CS).

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Section: Introductionmentioning

confidence: 99%

The value of genome-wide analysis in craniosynostosis

Topa,

Rohlin,

Fehr

et al. 2024

Front. Genet.

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“…Next-generation-based methods have enabled researchers to associate 154 out of approximately 300 epigenes with CPs (Squeo et al 2020;Boukas et al 2019;Kerkhof et al 2022;Bukowska-Olech et al 2022;Zollino et al 2017;Nava and Arboleda 2023). Recent studies have revealed that variants in epigenes lead to distinctive and disorder-specific DNA methylation patterns, known as episignatures (Levy et al 2021;Beck et al 2020;Sadikovic et al 2020).…”

Section: Introductionmentioning

confidence: 99%

Chromatinopathies: insight in clinical aspects and underlying epigenetic changes

Bukowska-Olech,

Majchrzak-Celińska,

Przyborska

et al. 2024

J Appl Genetics

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Chromatinopathies (CPs), a group of rare inborn defects characterized by chromatin state imbalance, have evolved from initially resembling Cornelia de Lange syndrome to encompass a wide array of genetic diseases with diverse clinical presentations. The CPs classification now includes human developmental disorders caused by germline mutations in epigenes, genes that regulate the epigenome. Recent advances in next-generation sequencing have enabled the association of 154 epigenes with CPs, revealing distinctive DNA methylation patterns known as episignatures.It has been shown that episignatures are unique for a particular CP or share similarities among specific CP subgroup. Consequently, these episignatures have emerged as promising biomarkers for diagnosing and treating CPs, differentiating subtypes, evaluating variants of unknown significance, and facilitating targeted therapies tailored to the underlying epigenetic dysregulation.The following review was conducted to collect, summarize, and analyze data regarding CPs in such aspects as clinical evaluation encompassing long-term patient care, underlying epigenetic changes, and innovative molecular and bioinformatic methodologies that have been devised for the assessment of CPs. We have also shed light on promising novel treatment options that have surfaced in recent research and presented a synthesis of ongoing clinical trials, contributing to the current understanding of the dynamic and evolving nature of CPs investigation.

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“…The metopic and sagittal sutures, respectively, split the frontal and parietal bones midway. Coronal sutures separate the frontal and parietal bones, and lambdoid sutures separate the parietal bones from the lone occipital bone [1].…”

Section: Introductionmentioning

confidence: 99%

Epilepsy in Patients with Craniosynostosis: A Systematic Review

Alanazi¹,

Alabdullatif²,

Alghamdi³

et al. 2022

Arch Pharm Pract

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If left untreated, craniosynostosis can cause neuropsychological impairments, psychosocial problems, and craniofacial deformities. Its association with epileptic seizures is unknown. This review investigated the incidence of epilepsy in patients with craniosynostosis. The Cochrane Library, Science Direct, Web of Science, EBSCO, and PubMed were all searched. Rayyan QCRI was used to filter study article titles and abstracts before full-text evaluations were conducted. In total, 11 studies involving 21456 patients with craniosynostosis were examined; more than half of the patients were men. The highest reported rate of preoperative epileptic seizures was 12.2%, and the lowest rate was 2.5%. The highest rate of post-operative epilepsy was 12.2%, and the lowest was 0.24%. There is a lack of literature on epileptic seizures as an outcome among craniosynostosis patients. The metabolic or hemodynamic events following craniosynostosis corrective surgeries were more significant. However, neurological manifestations, including epilepsy, require close monitoring. We found that syndromic craniosynostosis patients experienced more significant problems than non-syndromic patients.

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Results from Genetic Studies in Patients Affected with Craniosynostosis: Clinical and Molecular Aspects

Cited by 4 publications

References 56 publications

The value of genome-wide analysis in craniosynostosis

The value of genome-wide analysis in craniosynostosis

Chromatinopathies: insight in clinical aspects and underlying epigenetic changes

Epilepsy in Patients with Craniosynostosis: A Systematic Review

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