PMID- 17373680
OWN - NLM
STAT- MEDLINE
DCOM- 20070724
LR  - 20181201
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 28
IP  - 7
DP  - 2007 Jul
TI  - Overexpression of the C-type natriuretic peptide (CNP) is associated with 
      overgrowth and bone anomalies in an individual with balanced t(2;7) 
      translocation.
PG  - 724-31
AB  - Longitudinal bone growth is determined by the process of endochondral 
      ossification in the cartilaginous growth plate, which is located at both ends of 
      vertebrae and long bones and involves many systemic hormones and local 
      regulators. We report the molecular characterization of a de novo balanced 
      t(2;7)(q37.1;q21.3) translocation in a young female with Marfanoid habitus and 
      skeletal anomalies. The translocation was characterized by fluorescence in situ 
      hybridization (FISH), checked for other abnormalities by array-comparative 
      genomic hybridization (CGH), and finally, the breakpoints were cloned, sequenced, 
      and compared. Biochemical dosage was applied to study the possible mechanisms 
      that may cause the proposita's phenotype. The breakpoint on chromosome 2 disrupts 
      the hypothetical gene MGC42174 (HUGO-approved symbol DIS3L2) and is located in 
      the proximity of the NPPC gene coding for C-type natriuretic peptide (CNP), a 
      molecule that regulates endochondral bone growth. CNP plasma concentration was 
      doubled in the proband compared to five normal controls, while NPPC was 
      substantially overexpressed in her fibroblasts. A transgenic mouse generated to 
      target NPPC overexpression in bone showed a phenotype highly reminiscent of the 
      patient's phenotype. The breakpoint on chromosome 7 is localized proximally at 
      about 75 kb from the COL1A2 gene. The COL1A2 allele on the derivative chromosome 
      was strongly underexpressed in fibroblasts, but total collagen was not 
      significantly different from controls. Several evidences support the conclusion 
      that the proband's abnormal phenotype is associated with C-type natriuretic 
      peptide overexpression.
CI  - (c) 2007 Wiley-Liss, Inc.
FAU - Bocciardi, Renata
AU  - Bocciardi R
AD  - Laboratory of Molecular Genetics, G. Gaslini Institute, Genova, Italy.
FAU - Giorda, Roberto
AU  - Giorda R
FAU - Buttgereit, Jens
AU  - Buttgereit J
FAU - Gimelli, Stefania
AU  - Gimelli S
FAU - Divizia, Maria Teresa
AU  - Divizia MT
FAU - Beri, Silvana
AU  - Beri S
FAU - Garofalo, Silvio
AU  - Garofalo S
FAU - Tavella, Sara
AU  - Tavella S
FAU - Lerone, Margherita
AU  - Lerone M
FAU - Zuffardi, Orsetta
AU  - Zuffardi O
FAU - Bader, Michael
AU  - Bader M
FAU - Ravazzolo, Roberto
AU  - Ravazzolo R
FAU - Gimelli, Giorgio
AU  - Gimelli G
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Collagen Type I)
RN  - 0 (DNA Primers)
RN  - 127869-51-6 (Natriuretic Peptide, C-Type)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Adolescent
MH  - Animals
MH  - Base Sequence
MH  - Bone Development/*genetics
MH  - Bone and Bones/*abnormalities
MH  - *Chromosomes, Human, Pair 2
MH  - *Chromosomes, Human, Pair 7
MH  - Collagen/genetics
MH  - Collagen Type I
MH  - DNA Primers
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Mice
MH  - Mice, Transgenic
MH  - Natriuretic Peptide, C-Type/genetics/*metabolism
MH  - *Translocation, Genetic
EDAT- 2007/03/22 09:00
MHDA- 2007/07/25 09:00
CRDT- 2007/03/22 09:00
PHST- 2007/03/22 09:00 [pubmed]
PHST- 2007/07/25 09:00 [medline]
PHST- 2007/03/22 09:00 [entrez]
AID - 10.1002/humu.20511 [doi]
PST - ppublish
SO  - Hum Mutat. 2007 Jul;28(7):724-31. doi: 10.1002/humu.20511.