Genital lentigines in a 6-year-old boy with a family history of Cowden's disease: clinical and genetic evidence of the linkage between Bannayan-Riley-Ruvacalba syndrome and Cowden's disease.
BACKGROUND
In 1997, it was reported that a PTEN gene deletion, a common genetic mutation in Cowden's disease (CD), was identified in a patient with Bannayan-Riley-Ruvacalba (BRR), suggesting that the two diseases were allelic. However, the clinical overlap between the two diseases has largely remained unclear.


OBJECTIVE
To confirm the genetic and clinical association in a family segregating both CD and BRR.


METHODS
Clinical evaluation and genetic analysis using a denaturing gradient gel electrophoresis (DGGE), temporal temperature gradient electrophoresis (TTGE), and DNA sequencing techniques.


RESULTS
Our patient presents with typical BRR clinical manifestations, including multiple lentigines on his penis, while his mother presents with typical manifestations of CD, including multiple malignancies. Genetic analyses of leukocytes from the patient and his mother showed mutations in exon 8 that was identified as the presumably truncating mutation R335X.


CONCLUSIONS
This report provides clinical evidence that both BRR and CD are closely related and confirms the PTEN gene mutation in BRR and CD patients segregating in the same family, thus confirming the genetic linkage between the two genodermatoses.
Blum
R R
RR
Department of Dermatology, Mount Sinai Medical Center, New York, New York, USA 10029, USA.
Rahimizadeh
A
A
Kardon
N
N
Lebwohl
M
M
Wei
H
H
D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D019465:Craniofacial Abnormalities / Q000235:genetics*; D003937:Diagnosis, Differential; D017353:Gene Deletion; D008040:Genetic Linkage; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007911:Lentigo / Q000235:genetics* / Q000473:pathology; D008297:Male; D051059:PTEN Phosphohydrolase; D010409:Penile Diseases / Q000235:genetics / Q000473:pathology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human