Huntington’s disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes.
1. Brain. 2003 Jul;126(Pt 7):1599-603. Epub 2003 May 6.
Huntington’s disease-like phenotype due to trinucleotide repeat expansions in the
TBP and JPH3 genes.
Stevanin G(1), Fujigasaki H, Lebre AS, Camuzat A, Jeannequin C, Dode C, Takahashi
J, San C, Bellance R, Brice A, Durr A.
Author information:
(1)INSERM U289, Hôpital de la Salpêtrière, 47 Bd de l’Hôpital, 75013 Paris,
France.
We report a group of 252 patients with a Huntington’s disease-like (HDL)
phenotype, including 60 with typical Huntington’s disease, who had tested
negative for pathological expansions in the IT15 gene, the major mutation in
Huntington’s disease. They were screened for repeat expansions in two other genes
involved in HDL phenotypes: those encoding the junctophilin-3 (JPH3/HDL2) and
prion (PRNP/HDL1) proteins. In addition, because of the clinical overlap between
patients with HDL disease and autosomal dominant cerebellar ataxia or
dentatorubral and pallidoluysian atrophy (DRPLA), we investigated trinucleotide
repeat expansions in genes encoding the TATA-binding protein (TBP/SCA17) and
atrophin-1 (DRPLA). Two patients carried 43 and 50 uninterrupted CTG repeats in
the JPH3 gene. Two other patients had 44 and 46 CAA/CAG repeats in the TBP gene.
Patients with expansions in the TBP or JPH3 genes had HDL phenotypes
indistinguishable from Huntington’s disease. Taking into account patients with
typical Huntington’s disease, their frequencies were evaluated as 3% each in our
series of typical HDL patients. Interestingly, incomplete penetrance of the 46
CAA/CAG repeat in the TBP gene was observed in a 59-year-old transmitting, but
healthy, parent. Furthermore, we report a new configuration of the expanded TBP
allele, with 11 repeats on the first polymorphic stretch of CAGs. Expansions in
the DRPLA gene and insertions in the PRNP gene were not found in our group of
patients. Further genetic heterogeneity of the HDL phenotype therefore exists.
DOI: 10.1093/brain/awg155
PMID: 12805114 [Indexed for MEDLINE]