TY - JOUR
T1 - Haploinsufficiency of the miR-873/miR-876 microRNA cluster is associated with craniofacial abnormalities
AU - Koufaris, Costas
AU - Papagregoriou, Gregoris
AU - Kousoulidou, Ludmila
AU - Moutafi, Maria
AU - Tauber, Maithé
AU - Jouret, Béatrice
AU - Kieffer, Isabelle
AU - Deltas, Constantinos
AU - Tanteles, George A.
AU - Anastasiadou, Violetta
AU - Patsalis, Philippos C.
AU - Sismani, Carolina
PY - 2015/4/25
Y1 - 2015/4/25
N2 - MicroRNA haploinsufficiency has been associated with developmental defects in only a limited number of cases. Here we report a de novo genomic microdeletion that includes the LINGO2 gene as well as two microRNA genes, MIR873 and MIR876, in a patient with craniofacial abnormalities - in particular macrocephaly and hypertelorism - and learning difficulties. Subsequent analysis revealed that the microRNAs affected by this de novo microdeletion form a mammalian-lineage, neuronal tissue-enriched cluster. In addition, bioinformatic analysis and experimental data indicate that miR-873 is involved in the regulation of the Hedgehog signaling, an essential pathway involved in craniofacial patterning and differentiation. Collectively these observations are consistent with a role of the miR-873/miR-876 microRNA cluster in physiological cranial bone development and indicate that mutations affecting these microRNAs could be a rare cause of developmental defect in humans.
AB - MicroRNA haploinsufficiency has been associated with developmental defects in only a limited number of cases. Here we report a de novo genomic microdeletion that includes the LINGO2 gene as well as two microRNA genes, MIR873 and MIR876, in a patient with craniofacial abnormalities - in particular macrocephaly and hypertelorism - and learning difficulties. Subsequent analysis revealed that the microRNAs affected by this de novo microdeletion form a mammalian-lineage, neuronal tissue-enriched cluster. In addition, bioinformatic analysis and experimental data indicate that miR-873 is involved in the regulation of the Hedgehog signaling, an essential pathway involved in craniofacial patterning and differentiation. Collectively these observations are consistent with a role of the miR-873/miR-876 microRNA cluster in physiological cranial bone development and indicate that mutations affecting these microRNAs could be a rare cause of developmental defect in humans.
KW - Craniofacial
KW - Developmental defect
KW - Haploinsufficiency
KW - Hedgehog
KW - MiR-873
KW - MiR-876
UR - http://www.scopus.com/inward/record.url?scp=84924532864&partnerID=8YFLogxK
U2 - 10.1016/j.gene.2015.02.018
DO - 10.1016/j.gene.2015.02.018
M3 - Article
C2 - 25680557
AN - SCOPUS:84924532864
SN - 0378-1119
VL - 561
SP - 95
EP - 100
JO - Gene
JF - Gene
IS - 1
ER -