Polycystic liver disease genes: Practical considerations for genetic testing.

Area of Science:

• Hepatology
• Medical Genetics
• Monogenic Disorders

Background:

• Polycystic liver is a hallmark of several monogenic disorders, including autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), and autosomal dominant polycystic liver disease (ADPLD).
• While ADPKD and ARPKD are primarily caused by a few specific genes, ADPLD has a more complex genetic basis involving at least six genes, with a significant portion of cases unexplained by current genetic knowledge.
• Genetic testing is standard for diagnosing polycystic kidney disease (PKD) and guiding renal therapy decisions.

Purpose of the Study:

• To elucidate the significance of genetic testing specifically in patients diagnosed with autosomal dominant polycystic liver disease (ADPLD).
• To address the current limitations in understanding genotype-phenotype correlations in ADPLD, which often leads to underutilization of genetic screening in pure ADPLD cases.

Main Methods:

• Review of current literature on genetic testing in polycystic liver diseases.
• Analysis of the genetic basis of ADPLD, including known causative genes and unexplained cases.
• Discussion of the clinical utility and challenges of genetic testing in ADPLD.

Main Results:

• ADPLD is genetically heterogeneous, with multiple genes implicated, yet over half of cases remain genetically uncharacterized.
• Genetic testing for ADPLD is often overlooked due to limited genotype-phenotype correlation data.
• Current genetic testing primarily focuses on confirming PKD likelihood and assessing the need for renal therapy.

Conclusions:

• Genetic testing plays a vital role in the accurate diagnosis and management of ADPLD.
• Further research into genotype-phenotype correlations is essential to improve genetic screening and patient care for ADPLD.
• Clarifying the essence of genetic testing is critical for advancing the understanding and treatment of ADPLD.