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

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Maryam Khalid
Areej Munir
Abdullah Sajid
Ammar Mehfooz
Usama Khalil Qadri
Shahzeera Begum
Mohsan Aslam
Rehmatullah Zadran
Mehak Khalid
Waseem Ahmed

Abstract

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.

Article Details

How to Cite
Khalid, M., Areej Munir, Abdullah Sajid, Ammar Mehfooz, Usama Khalil Qadri, Shahzeera Begum, Mohsan Aslam, Rehmatullah Zadran, Mehak Khalid, & Waseem Ahmed. (2024). Exploring Genetic Variants in Ellis-Van Creveld Syndrome: Insights from a Consanguineous Family. Journal of Health and Rehabilitation Research, 4(2), 1105–1110. https://doi.org/10.61919/jhrr.v4i2.964
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Articles
Author Biographies

Maryam Khalid, Isra University Islamabad Pakistan.

Department of Medical Lab Technology, Al Nafees Medical College, Isra University, Islamabad, Pakistan.

Areej Munir, Isra University Islamabad Pakistan.

Department of Medical Lab Technology, Al Nafees Medical College, Isra University, Islamabad, Pakistan.

Abdullah Sajid, Isra University Islamabad Pakistan.

Department of Medical Lab Technology, Al Nafees Medical College, Isra University, Islamabad, Pakistan.

Ammar Mehfooz, Isra University Islamabad Pakistan.

Department of Medical Lab Technology, Al Nafees Medical College, Isra University, Islamabad, Pakistan.

Usama Khalil Qadri, Shaheed Zulfiqar Ali Bhutto Medical University Islamabad Pakistan.

Department of Molecular Biology, Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad, Pakistan.

Shahzeera Begum, Isra University Islamabad Pakistan.

Department of Medical Lab Technology, Al Nafees Medical College, Isra University, Islamabad, Pakistan.

Mohsan Aslam, Isra University Islamabad Pakistan.

Department of Medical Lab Technology, Al Nafees Medical College, Isra University, Islamabad, Pakistan.

Rehmatullah Zadran, National Infectious Disease Laboratory Kabul Afghanistan.

WHO-Surveillance Department, National Infectious Disease Laboratory, Kabul, Afghanistan.

Mehak Khalid, MBBS MCPS-Gynaecologist.

MBBS MCPS-Gynaecologist.

Waseem Ahmed, Quaid-i-Azam University Islamabad Pakistan

Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, Pakistan.

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