Molecular diagnosis of an infant with TSC2/PKD1 contiguous gene syndrome

Area of Science:

• Genetics
• Pediatrics
• Molecular Biology

Background:

• Cardiac rhabdomyoma can be a manifestation of Tuberous Sclerosis Complex (TSC).
• Polycystic Kidney Disease 1 (PKD1) gene mutations are associated with autosomal dominant polycystic kidney disease.
• Contiguous gene deletions involving TSC2 and PKD1 are rare genetic disorders.

Purpose of the Study:

• To report a case of TSC2/PKD1 contiguous gene syndrome diagnosed in an infant.
• To highlight the utility of molecular diagnostics in identifying complex genetic deletions.
• To emphasize the importance of early detection and multidisciplinary management for this multisystem disease.

Main Methods:

• Targeted panel sequencing was employed for genetic analysis.
• Quantitative polymerase chain reaction (qPCR) was used to confirm gross monoallelic deletion.
• Clinical data from a 1-month-old Japanese infant with cardiac rhabdomyoma was reviewed.

Main Results:

• A diagnosis of TSC2/PKD1 contiguous gene syndrome was established.
• A gross monoallelic deletion encompassing exons 19-42 of TSC2 and exons 2-46 of PKD1 was identified.
• The patient presented with cardiac rhabdomyoma, indicating potential for other systemic manifestations.

Conclusions:

• Early molecular diagnosis of TSC2/PKD1 contiguous gene syndrome is crucial.
• This diagnosis facilitates the early detection of bilateral renal cyst formation.
• Multidisciplinary follow-up is essential for managing the multisystemic aspects of this disease.