Clinical variability in DYNC2H1-related skeletal ciliopathies includes Ellis-van Creveld syndrome

Piceci‐Sparascio, Francesca; Micale, Lucia; Torres, Bárbara; Guida, Valentina; Consoli, Federica; Torrente, Isabella; Onori, Annamaria; Frustaci, Emanuela; D'Asdia, Maria Cecilia; Petrizzelli, Francesco; Bernardini, Laura; Mancini, Cecilia; Soli, Fiorenza; Cocciadiferro, Dario; Guadagnolo, Daniele; Mastromoro, Gioia; Putotto, Carolina; Fontana, Franco; Brunetti‐Pierri, Nicola; Novelli, Antonio; Pizzuti, Antonio; Marino, Bruno; Digilio, María Cristina; Mazza, Tommaso; Dallapiccola, Bruno; Ruiz‐Pérez, Víctor L.; Tartaglia, Marco; Castori, Marco; Luca, Alessandro De

doi:10.1038/s41431-022-01276-7

Cited by 5 publications

(2 citation statements)

References 16 publications

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“…The phenotypic variability of EVC often complicates its diagnosis, with affected individuals displaying a range of clinical manifestations. Prenatal abnormalities, such as narrow thorax, extreme shortening of long bones, polydactyly, and cardiac anomalies, can be detected as early as the 18th week of gestation (3). Cardiac malformations, including single atrium and defects in the mitral and tricuspid valves, are present in about 50-60% of EVC patients and are major determinants of patient longevity (4).…”

Section: Introductionmentioning

confidence: 99%

Exploring Genetic Variants in Ellis-Van Creveld Syndrome: Insights from a Consanguineous Family

Khalid,

Areej Munir,

Abdullah Sajid

et al. 2024

JHRR

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Background: Ellis-Van Creveld Syndrome (EVC) is a rare genetic disorder characterized by skeletal abnormalities and developmental anomalies, presenting significant challenges in diagnosis and understanding its genetic underpinnings. Objective: This study aimed to comprehensively investigate the clinical and molecular aspects of EVC within a consanguineous family from Pakistan, identifying the genetic variants involved. Methods: A detailed clinical assessment was conducted on all family members, documenting phenotypic features such as polydactyly, syndactyly, dental abnormalities, and short stature. Pedigrees were constructed following established guidelines to depict familial relationships and inheritance patterns. Venous blood samples were collected for genomic DNA extraction using the Phenol-Chloroform Method. Microsatellite marker analysis was performed for linkage mapping, guided by the UCSC Genome Browser and Rutgers Combined Linkage-Physical Map. Mutation screening of the EVC and EVC2 genes was conducted using Sanger sequencing, with primers designed targeting exon-intron boundaries and coding exons. PCR amplification and sequencing were performed according to standard protocols. Data analysis was carried out using SPSS version 25. Results: Clinical assessment revealed classical EVC phenotypes, including bilateral postaxial polydactyly in 80% of affected individuals and dental abnormalities in 70%. Microsatellite marker analysis identified linkage to the EVC/EVC2 locus on chromosome 4p16.2. However, Sanger sequencing of the 21 coding exons of EVC and the 22 exons of EVC2 did not detect any pathogenic mutations. Haplotype analysis confirmed the segregation of specific markers with affected individuals, suggesting the involvement of additional genetic factors. Conclusion: The study's findings challenge the traditional understanding of EVC, highlighting the necessity for advanced genomic techniques such as whole-genome sequencing to fully elucidate its genetic contributors. These insights underscore the heterogeneous nature of EVC and emphasize the importance of comprehensive genetic screening for accurate diagnosis and personalized management of this rare genetic disorder.

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Section: Introductionmentioning

confidence: 99%

Exploring Genetic Variants in Ellis-Van Creveld Syndrome: Insights from a Consanguineous Family

Khalid,

Areej Munir,

Abdullah Sajid

et al. 2024

JHRR

View full text Add to dashboard Cite

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“…Neyroud et al report that LARS2 variants present with isolated premature ovarian failure and a linked comment by Vona [12,13]. The clinical spectrum of DYNC2H1 variants is further described with Ellis van-Creveld like presentations noted [14].…”

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confidence: 99%