Severe Lhermitte-Duclos disease with unique germline mutation of PTEN

Germline mutations in the PTEN gene have recently been identified in some individuals with Cowden disease (CD), Lhermitte-Duclos disease (LDD), and Bannayan-Zonana syndrome. We report on a patient with CD and LDD in whom a unique de novo germline missense mutation is present in the PTEN gene. Direct sequence analysis detected a transitional change (T-->C) at nucleotide 335, resulting in substitution of the amino acid proline for leucine. The mutation is in exon 5, which has been proposed as a "hot-spot" for germline mutations. Comparison of this patient's clinical course with the previously reported cases of CD and LDD shows more extensive and more severe clinical findings than reported previously. Findings in this patient contribute to the current understanding of germline PTEN mutations and clinical outcome.