Medical case reports in the age of genomic medicine

Area of Science:

• Genetics
• Medical Literature
• Precision Medicine

Background:

• Case reports, historically vital in medical literature, face challenges due to bias.
• The shift towards precision medicine highlights the value of case reports for rare genetic variants.
• Many unexplained Mendelian diseases are linked to rare heterozygous alleles, de novo mutations, or compound heterozygous mutations within families.

Purpose of the Study:

• To re-evaluate the significance of the case report format in the era of precision medicine.
• To emphasize the role of case reports in elucidating disease mechanisms driven by rare genetic variants.
• To demonstrate the potential of case studies in identifying novel therapeutic targets.

Main Methods:

• Review of existing medical literature on case reports and genetic diseases.
• Analysis of empirical evidence linking rare genetic variants to Mendelian diseases.
• Examination of how allelic series and extreme phenotypes in individual cases contribute to understanding disease.

Main Results:

• Rare genetic variants, often family-specific, are key to many unexplained Mendelian diseases.
• Elucidating phenotypes of rare variants provides unique insights into disease mechanisms.
• Individual cases and allelic series expand knowledge of both clinical and laboratory phenotypes.
• Resolving extreme phenotypes in single cases can uncover therapeutic strategies applicable to more common diseases.

Conclusions:

• Case reports remain valuable tools, particularly for understanding rare genetic variants and disease mechanisms.
• The case report format is essential for advancing precision medicine by detailing rare genetic conditions.
• Investigating individual cases, irrespective of disease prevalence, can lead to significant therapeutic discoveries.