Genotype-phenotype correlation in Prader-Willi syndrome: A large-sample analysis in China

Area of Science:

• Genetics
• Pediatrics
• Rare Diseases

Background:

• The genotype-phenotype relationship in Prader-Willi syndrome (PWS) is vital for understanding clinical manifestations.
• Identifying specific gene alterations' impact on PWS phenotypes aids in early diagnosis and intervention strategies.

Purpose of the Study:

• To investigate the influence of distinct genetic changes on PWS clinical symptoms.
• To evaluate the significance of early screening and intervention for PWS based on genotype-phenotype correlations.

Main Methods:

• Retrospective analysis of data from 586 PWS patients with confirmed molecular diagnosis and genotyping.
• Data extracted from the XiaoPang Weili Rare Disease Care Center database, including demographics, pregnancy, endocrine, growth, and clinical phenotypes.
• Comparison of genotype (deletion, uniparental disomy (UPD), imprinting defect (ID)) and phenotype relationships.

Main Results:

• Deletion type (83.8%) was the most common PWS genotype, followed by UPD (10.9%) and ID (5.3%).
• Deletion group showed significantly higher rates of skin hypopigmentation (88.8% vs. 68.4%) and epilepsy (15.9% vs. 7.6%) compared to non-deletion types.
• Significant intergroup differences observed in language development delay (>2 years), with deletion type highest, followed by UPD, then ID. Obesity and hyperphagia rates were also higher in the deletion group.

Conclusions:

• Significant genotype-phenotype differences exist among deletion, UPD, and ID types in PWS.
• Deletion genotype is associated with increased likelihood of lighter skin, obesity, hyperphagia, language delay, and epilepsy.
• Findings enhance clinical understanding of how PWS molecular etiologies influence specific patient phenotypes.