Copy number variations: reliable diagnostic markers for Prader-Willi patients

Shehab, Marwa I.K.; Amr, Khalda S.; Afifi, Hanan H.; Khedr, Azzah A.; Abd-Elnaby, Azza E.; El-Bassyouni, Hala T.

doi:10.21608/epj.2025.407752

Copy number variations: reliable diagnostic markers for Prader-Willi patients

Document Type : Original Article

Authors

¹ Department of aHuman Cytogenetics, Institute of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt

² Departments ofMolecular Genetics,Institute of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt

³ Departments ofClinical Genetics, Institute of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt

10.21608/epj.2025.407752

Abstract

Background
Syndromic obesity is characterized by a specific set of associated clinical features, but the similarity between different obesity syndromes can make it hard to diagnose accurately. Prader-Willi syndrome (PWS) is the most common type of syndromic obesity. A variety of molecular and cytogenetic techniques may be needed for the diagnosis of obesity. Multiplex ligation-dependent probe amplification (MLPA) helps by allowing the study of multiple specific genetic regions at once. This makes it an effective screening tool for large groups of patients who may have deletions or duplications in specific genes.
Objective
We aim to establish a precise diagnostic scheme for early diagnosis that yields proper early intervention to prevent the development of morbid obesity and intellectual disability, which render a great burden on both health services and the families of the patients.
Materials and methods
Combined cytogenetic fluorescence in-situ hybridization and methylation studies using MLPA was conducted on 20 patients who were clinically suspected to have PWS.
Results and conclusion
We analyzed 20 suspected PWS cases descending from 18 unrelated families and 20 healthy controls matching age and sex, using MS-MLPA PWS/AS probemix (MRC-Holland) enables the identification of copy number variations or abnormal methylation patterns.
One patient (P18) had PW deletion, which was evident by the reduced copy number ratio, and uniparental disomy was evident in two unrelated patients (P2 and P12). The results indicate that our study identified one typical PWS deletion and two uniparental disomy cases among three patients from distinct families, suggesting that atypical deletions are infrequent in this cohort. This research represents the first exploration of PWS in Egyptian patients using MLPA.

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