Abstract
The human chromosome 14q32 carries a cluster of imprinted genes which include the paternally expressed genes (PEGs) DLK1 and RTL1, as well as the maternally expressed genes (MEGs) MEG3, RTL1as, and MEG8. PEGs and MEGs expression at the 14q32.2-imprinted region are regulated by two differentially methylated regions (DMRs): the IG-DMR and the MEG3-DMR, which are respectively methylated on the paternal and unmethylated on the maternal chromosome 14 in most cells. Genetic and epigenetic abnormalities affecting these imprinted gene clusters result in two different phenotypes currently known as maternal upd(14) syndrome and paternal upd(14) syndrome. However, only few patients carrying a maternal deletion at the 14q32.2-imprinted critical region have been reported so far. Here we report on the first patient with a maternal de novo deletion of 160kb at the 14q32.2 chromosome that does not involves the IG-DMR or the MEG3-DMR but elicits a full upd(14)pat syndrome's phenotype encompassing the three mentioned MEGs. By the analysis of this unique genotype-phenotype correlation, we further widen the spectrum of the congenital anomalies associated to this rare disorder and we propose that the paternally expressed imprinted RTL1 gene, as well as its maternally expressed RTL1as antisense transcript, may play a prominent causative role.
| Original language | English |
|---|---|
| Pages (from-to) | 3130-3138 |
| Number of pages | 9 |
| Journal | American Journal of Medical Genetics, Part A |
| Volume | 167 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2015 |
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Keywords
- "coat-hanger" rib sign
- 14q32.2 imprinted region
- 14q32.2 maternal deletion
- IG-DMR
- MEG3 gene
- MEG3-DMR
- Paternal uniparental disomy chromosome 14 [upd(14)pat]
- RTL1as gene
- Skeletal dysplasia
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Paternal uniparental disomy chromosome 14-like syndrome due a maternal de novo 160kb deletion at the 14q32.2 region not encompassing the IG- and the MEG3-DMRs : Patient report and genotype-phenotype correlation. / Corsello, Giovanni; Salzano, Emanuela; Vecchio, Davide; Antona, Vincenzo; Grasso, Marina; Malacarne, Michela; Carella, Massimo; Palumbo, Pietro; Piro, Ettore; Giuffrè, Mario.
In: American Journal of Medical Genetics, Part A, Vol. 167, No. 12, 01.12.2015, p. 3130-3138.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Paternal uniparental disomy chromosome 14-like syndrome due a maternal de novo 160kb deletion at the 14q32.2 region not encompassing the IG- and the MEG3-DMRs
T2 - Patient report and genotype-phenotype correlation
AU - Corsello, Giovanni
AU - Salzano, Emanuela
AU - Vecchio, Davide
AU - Antona, Vincenzo
AU - Grasso, Marina
AU - Malacarne, Michela
AU - Carella, Massimo
AU - Palumbo, Pietro
AU - Piro, Ettore
AU - Giuffrè, Mario
PY - 2015/12/1
Y1 - 2015/12/1
N2 - The human chromosome 14q32 carries a cluster of imprinted genes which include the paternally expressed genes (PEGs) DLK1 and RTL1, as well as the maternally expressed genes (MEGs) MEG3, RTL1as, and MEG8. PEGs and MEGs expression at the 14q32.2-imprinted region are regulated by two differentially methylated regions (DMRs): the IG-DMR and the MEG3-DMR, which are respectively methylated on the paternal and unmethylated on the maternal chromosome 14 in most cells. Genetic and epigenetic abnormalities affecting these imprinted gene clusters result in two different phenotypes currently known as maternal upd(14) syndrome and paternal upd(14) syndrome. However, only few patients carrying a maternal deletion at the 14q32.2-imprinted critical region have been reported so far. Here we report on the first patient with a maternal de novo deletion of 160kb at the 14q32.2 chromosome that does not involves the IG-DMR or the MEG3-DMR but elicits a full upd(14)pat syndrome's phenotype encompassing the three mentioned MEGs. By the analysis of this unique genotype-phenotype correlation, we further widen the spectrum of the congenital anomalies associated to this rare disorder and we propose that the paternally expressed imprinted RTL1 gene, as well as its maternally expressed RTL1as antisense transcript, may play a prominent causative role.
AB - The human chromosome 14q32 carries a cluster of imprinted genes which include the paternally expressed genes (PEGs) DLK1 and RTL1, as well as the maternally expressed genes (MEGs) MEG3, RTL1as, and MEG8. PEGs and MEGs expression at the 14q32.2-imprinted region are regulated by two differentially methylated regions (DMRs): the IG-DMR and the MEG3-DMR, which are respectively methylated on the paternal and unmethylated on the maternal chromosome 14 in most cells. Genetic and epigenetic abnormalities affecting these imprinted gene clusters result in two different phenotypes currently known as maternal upd(14) syndrome and paternal upd(14) syndrome. However, only few patients carrying a maternal deletion at the 14q32.2-imprinted critical region have been reported so far. Here we report on the first patient with a maternal de novo deletion of 160kb at the 14q32.2 chromosome that does not involves the IG-DMR or the MEG3-DMR but elicits a full upd(14)pat syndrome's phenotype encompassing the three mentioned MEGs. By the analysis of this unique genotype-phenotype correlation, we further widen the spectrum of the congenital anomalies associated to this rare disorder and we propose that the paternally expressed imprinted RTL1 gene, as well as its maternally expressed RTL1as antisense transcript, may play a prominent causative role.
KW - "coat-hanger" rib sign
KW - 14q32.2 imprinted region
KW - 14q32.2 maternal deletion
KW - IG-DMR
KW - MEG3 gene
KW - MEG3-DMR
KW - Paternal uniparental disomy chromosome 14 [upd(14)pat]
KW - RTL1as gene
KW - Skeletal dysplasia
UR - http://www.scopus.com/inward/record.url?scp=84959323283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959323283&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.37293
DO - 10.1002/ajmg.a.37293
M3 - Article
VL - 167
SP - 3130
EP - 3138
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 12
ER -