A cluster of translocation breakpoints in 2q37 is associated with overexpression of NPPC in patients with a similar overgrowth phenotype.
Overexpression of the C-type natriuretic peptide, encoded by the NPPC gene in 2q37.1, was recently reported in a patient presenting an overgrowth phenotype and a balanced t(2;7)(q37.1;q21.3) translocation. We present clinical, cytogenetic, and molecular data from two additional patients carrying balanced translocations involving the same 2q37.1 chromosome band and chromosomes 8 and 13, respectively. The clinical phenotype of these patients is very similar to the first patient described. In addition to the overgrowth syndrome, there is evidence of generalized cartilage dysplasia. In these two new cases, we found overexpression of NPPC, confirming that this unusual overgrowth phenotype in humans is due to the overexpression of this gene. The involvement of three different chromosomes and a cluster of breakpoints around the NPPC gene suggests that the overexpression of this gene in translocation patients could be due to its separation from a negative regulatory element located on chromosome 2, which would constitute a previously undescribed mutational mechanism.
Assistance Publique-Hôpitaux de Marseille, Hôpital d'Enfants de La Timone, Departement de Génétique, Marseille, France.
Anne
A
Moncla
Chantal
C
Missirian
Pierre
P
Cacciagli
Eve
E
Balzamo
Laurence
L
Legeai-Mallet
Jean-Luc
JL
Jouve
Brigitte
B
Chabrol
Martine
M
Le Merrer
Ghislaine
G
Plessis
Laurent
L
Villard
Nicole
N
Philip
D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005786:Gene Expression Regulation; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000235:genetics*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
D020098:Natriuretic Peptide, C-Type