An InDel in Phospholipase-C-B-1 Is Linked with Euthyroid Multinodular Goiter

Area of Science:

• Genetics
• Endocrinology
• Molecular Biology

Background:

• Multinodular goiter (MNG) is common, yet its genetic predisposition is poorly understood.
• A family with early-onset MNG and associated papillary thyroid carcinoma (PTC) was previously identified.

Purpose of the Study:

• To identify genetic variations associated with MNG predisposition.
• To investigate the role of identified variants in familial and sporadic MNG.

Main Methods:

• Genome-wide linkage analysis and next-generation sequencing were employed.
• Copy number variation analysis identified a specific intronic InDel in the PLCB1 gene.
• The identified InDel was genotyped in Caucasian cohorts with MNG and PTC.

Main Results:

• An intronic InDel in the PLCB1 gene was found in all affected family members and carriers.
• This InDel was significantly more frequent in unrelated MNG patients compared to controls.
• PLCB1 transcript levels were elevated in thyroids with the InDel, suggesting a functional impact.

Conclusions:

• The intronic PLCB1 InDel is the first identified variant in familial MNG and a subset of sporadic MNG.
• This variant may contribute to MNG through overexpression and increased PLC activity.
• The PLCB1 InDel could serve as a biomarker for MNG progression to PTC.