A novel complex genomic rearrangement affecting the KCNJ2 regulatory region causes a variant of Cooks syndrome

Cinque, Luigia; Micale, Lucia; Manara, Elena; Esposito, Andrea; Palumbo, Orazio; Chiariello, Andrea M.; Bianco, Simona; Bertelli, Matteo; Giuffrida, Maria Grazia; Bernardini, Laura; Notarangelo, Angelo; Nicodemi, Mario; Castori, Marco

doi:10.1007/s00439-021-02403-y

Cited by 3 publications

(2 citation statements)

References 26 publications

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“…Balanced chromosomal rearrangements, including inversions and translocations, occur between spatially adjacent or separated TADs, changing the position and/or orientation of DNA segments 27 . Balanced rearrangements cause pathological effects by placing genes and/or regulatory elements in different chromosomal environments, a phenomenon known as “TAD shuffling” 312 . TADs that experience balancing rearrangements result in abnormal gene expression due to disrupted enhancer–promoter interactions, enhancer hijacking effects, or positional effects (Figure 4B).…”

Section: D Genome Structural Variations and Diseasementioning

confidence: 99%

“… 27 Balanced rearrangements cause pathological effects by placing genes and/or regulatory elements in different chromosomal environments, a phenomenon known as “TAD shuffling”. 312 TADs that experience balancing rearrangements result in abnormal gene expression due to disrupted enhancer–promoter interactions, enhancer hijacking effects, or positional effects (Figure 4B ). 27 …”

Section: D Genome Structural Variations and Diseasementioning

confidence: 99%

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Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

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Linear DNA undergoes a series of compression and folding events, forming various three‐dimensional (3D) structural units in mammalian cells, including chromosomal territory, compartment, topologically associating domain, and chromatin loop. These structures play crucial roles in regulating gene expression, cell differentiation, and disease progression. Deciphering the principles underlying 3D genome folding and the molecular mechanisms governing cell fate determination remains a challenge. With advancements in high‐throughput sequencing and imaging techniques, the hierarchical organization and functional roles of higher‐order chromatin structures have been gradually illuminated. This review systematically discussed the structural hierarchy of the 3D genome, the effects and mechanisms of cis‐regulatory elements interaction in the 3D genome for regulating spatiotemporally specific gene expression, the roles and mechanisms of dynamic changes in 3D chromatin conformation during embryonic development, and the pathological mechanisms of diseases such as congenital developmental abnormalities and cancer, which are attributed to alterations in 3D genome organization and aberrations in key structural proteins. Finally, prospects were made for the research about 3D genome structure, function, and genetic intervention, and the roles in disease development, prevention, and treatment, which may offer some clues for precise diagnosis and treatment of related diseases.

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Section: D Genome Structural Variations and Diseasementioning

confidence: 99%

Section: D Genome Structural Variations and Diseasementioning

confidence: 99%

Three‐dimensional genome structure and function

Líu

Tsai

Yang

et al. 2023

MedComm

View full text Add to dashboard Cite

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Copy number variants at 4q31.3 affecting the regulatory region of FBXW7 associated with neurodevelopmental delay

Zhou,

Wang,

et al. 2024

Clinical Genetics

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Emerging research has demonstrated that genomic alterations disrupting topologically associated domains (TADs) and chromatin interactions underlie the pathogenic mechanisms of specific copy number variants (CNVs) in neurodevelopmental disorders. We report two patients with a de novo deletion and a duplication in chromosome 4q31, potentially causing FBX‐related neurodevelopmental syndrome by affecting the regulatory region of FBXW7. High‐throughput chromosome conformation capture (Hi‐C) analysis using available capture data in neural progenitor cells revealed the rewiring of the TAD boundary close to FBXW7. Both patients exhibited facial dysmorphisms, cardiac and limb abnormalities, and neurodevelopmental delays, showing significant clinical overlap with previously reported FBXW7‐related features. We also included an additional 10 patients with CNVs in the 4q31 region from the literature and the DECIPHER database for Hi‐C analysis, which confirmed that disruption of the regulatory region of FBXW7 likely contributes to the developmental defects observed in these patients.

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Pediatric Nail Disorders

Cedirian,

Alessandrini,

Starace

2024

Skin Appendage Disord

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Background: Pediatric nail disorders encompass a broad range of conditions. This article aimed to consolidate current knowledge on pediatric nail disorders to enhance diagnostic proficiency and clinical management among healthcare professionals. Summary: Pediatric nail disorders present a diagnostic challenge due to their diverse nature. Non-syndromic congenital nail disorders encompass various anomalies such as anonychia/hyponychia, congenital malalignment of the great toenail, and racket thumbs, each with distinct clinical presentations and genetic associations. Syndromic congenital nail disorders, often part of complex syndromes, are characterized by unique features and associated abnormalities. Acquired nail diseases in children, like Beau’s lines and onychomadesis, typically result from trauma or infection, while melanonychia, although rare in children, requires careful monitoring for potential malignant alterations, with consideration for biopsy in cases with concerning features. Key Messages: (1) Pediatric nail disorders may pose diagnostic challenges and require a comprehensive understanding of nail anatomy and development. (2) Congenital nail disorders encompass isolated anomalies and syndromic associations, necessitating thorough evaluation for associated systemic conditions. (3) Acquired nail diseases may indicate underlying trauma or systemic illness and require careful assessment.(4) Melanonychia in children requires ongoing monitoring and evaluation, emphasizing the importance of consistent follow-up and histopathological examination when necessary.

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A novel complex genomic rearrangement affecting the KCNJ2 regulatory region causes a variant of Cooks syndrome

Cited by 3 publications

References 26 publications

Three‐dimensional genome structure and function

Three‐dimensional genome structure and function

Copy number variants at 4q31.3 affecting the regulatory region of FBXW7 associated with neurodevelopmental delay

Pediatric Nail Disorders

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