Highly conserved non-coding sequences and the 18q critical region for short stature: a common mechanism of disease?
BACKGROUND
Isolated growth hormone deficiency (IGHD) and multiple pituitary hormone deficiency (MPHD) are heterogeneous disorders with several different etiologies and they are responsible for most cases of short stature. Mutations in different genes have been identified but still many patients did not present mutations in any of the known genes. Chromosomal rearrangements may also be involved in short stature and, among others, deletions of 18q23 defined a critical region for the disorder. No gene was yet identified.


RESULTS
We now report a balanced translocation X;18 in a patient presenting a breakpoint in 18q23 that was surprisingly mapped about 500 Kb distal from the short stature critical region. It separated from the flanking SALL3 gene a region enriched in highly conserved non-coding elements (HCNE) that appeared to be regulatory sequences, active as enhancers or silencers during embryonic development.


CONCLUSIONS
We propose that, during pituitary development, the 18q rearrangement may alter expression of 18q genes or of X chromosome genes that are translocated next to the HCNEs. Alteration of expression of developmentally regulated genes by translocation of HCNEs may represent a common mechanism for disorders associated to isolated chromosomal rearrangements.
Rizzolio
Flavio
F
Department of Biotechnologial Research (DIBIT), San Raffaele Scientific Institute, Milano, Italy.
Bione
Silvia
S
Sala
Cinzia
C
Tribioli
Carla
C
Ciccone
Roberto
R
Zuffardi
Orsetta
O
di Iorgi
Natascia
N
Maghnie
Mohamad
M
Toniolo
Daniela
D
D000818:Animals; D001827:Body Height / Q000235:genetics*; D002675:Child, Preschool; D002887:Chromosomes, Human, Pair 18; D047108:Embryonic Development / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice