Tooth agenesis and orofacial clefts represent the most common developmental anomalies and their co-occurrence is often reported in patients as well in animal models. The aim of the present systematic review is to thoroughly investigate the current literature (PubMed, EMBASE) to identify the genes and genomic loci contributing to syndromic or non-syndromic co-occurrence of tooth agenesis and orofacial clefts, to gain insight into the molecular mechanisms underlying their dual involvement in the development of teeth and facial primordia. Altogether, 84 articles including phenotype and genotype description provided 9 genomic loci and 26 gene candidates underlying the co-occurrence of the two congenital defects: MSX1, PAX9, IRF6, TP63, KMT2D, KDM6A, SATB2, TBX22, TGFα, TGFβ3, TGFβR1, TGFβR2, FGF8, FGFR1, KISS1R, WNT3, WNT5A, CDH1, CHD7, AXIN2, TWIST1, BCOR, OFD1, PTCH1, PITX2, and PVRL1. The molecular pathways, cellular functions, tissue-specific expression and disease association were investigated using publicly accessible databases (EntrezGene, UniProt, OMIM). The Gene Ontology terms of the biological processes mediated by the candidate genes were used to cluster them using the GOTermMapper (Lewis-Sigler Institute, Princeton University), speculating on six super-clusters: (a) anatomical development, (b) cell division, growth and motility, (c) cell metabolism and catabolism, (d) cell transport, (e) cell structure organization and (f) organ/system-specific processes. This review aims to increase the knowledge on the mechanisms underlying the co-occurrence of tooth agenesis and orofacial clefts, to pave the way for improving targeted (prenatal) molecular diagnosis and finally to reflect on therapeutic or ultimately preventive strategies for these disabling conditions in the future.

L’Agenesia Dentaria e le Schisi Oro-facciali costituiscono comuni anomalie dello sviluppo e la loro co-occorrenza è osservata spesso in pazienti ed in modelli animali. Lo scopo della presente revisione sistematica è quello di indagare a fondo la letteratura corrente (PubMed, EMBASE) per identificare i geni e loci genomici che contribuiscono alla co-occorrenza di Agenesia Dentaria e di Schisi Oro-facciali sindromiche e non-sindromiche, al fine di conoscere i meccanismi molecolari sottostanti al duplice coinvolgimento nello sviluppo dei denti e primordi facciali. Complessivamente sono stati analizzate 84 pubblicazioni comprendenti descrizioni fenotipiche e genotipiche riconducibili a 9 loci genomici e 26 geni candidati alla base della co-occorrenza dei due difetti congeniti: MSX1, PAX9, IRF6, TP63, KMT2D, KDM6A, SATB2, TBX22, TGFα, TGFβ3, TGFβR1, TGFβR2, FGF8, FGFR1, KISS1R, WNT3, Wnt5a, CDH1, CHD7, AXIN2, TWIST1, BCOR, OFD1, PTCH1, PITX2, e PVRL1. I percorsi molecolari, le funzioni cellulari, di espressione tessuto-specifica e di associazione con la patologia sono stati esaminati utilizzando database accessibili al pubblico (EntrezGene, UniProt, OMIM). I termini Gene Ontology dei processi biologici mediati da geni candidati sono stati usati per creare raggruppamenti utilizzando il GOTermMapper (Lewis-Sigler Institute, Princeton University), speculando su sei super-cluster: (a) sviluppo anatomico, (b) la divisione cellulare, crescita e motilità, (c) il metabolismo cellulare e catabolismo, (d) trasporto cellulare, (e) organizzazione struttura cellulare e (f) organo / processi specifici del sistema. Questa recensione ha lo scopo di aumentare la conoscenza sui meccanismi alla base della co-occorrenza di Agenesia Dentaria e di Schisi Oro-facciali, al fine di aprire la strada per migliorare la diagnosi molecolare mirata (prenatale) e, infine, per riflettere sullo sviluppo futuro di strategie terapeutiche o preventive per queste condizioni invalidanti.

Tooth agenesis and orofacial clefting: genetic brothers in arms?

RUBINI, Michele;
2016

Abstract

Tooth agenesis and orofacial clefts represent the most common developmental anomalies and their co-occurrence is often reported in patients as well in animal models. The aim of the present systematic review is to thoroughly investigate the current literature (PubMed, EMBASE) to identify the genes and genomic loci contributing to syndromic or non-syndromic co-occurrence of tooth agenesis and orofacial clefts, to gain insight into the molecular mechanisms underlying their dual involvement in the development of teeth and facial primordia. Altogether, 84 articles including phenotype and genotype description provided 9 genomic loci and 26 gene candidates underlying the co-occurrence of the two congenital defects: MSX1, PAX9, IRF6, TP63, KMT2D, KDM6A, SATB2, TBX22, TGFα, TGFβ3, TGFβR1, TGFβR2, FGF8, FGFR1, KISS1R, WNT3, WNT5A, CDH1, CHD7, AXIN2, TWIST1, BCOR, OFD1, PTCH1, PITX2, and PVRL1. The molecular pathways, cellular functions, tissue-specific expression and disease association were investigated using publicly accessible databases (EntrezGene, UniProt, OMIM). The Gene Ontology terms of the biological processes mediated by the candidate genes were used to cluster them using the GOTermMapper (Lewis-Sigler Institute, Princeton University), speculating on six super-clusters: (a) anatomical development, (b) cell division, growth and motility, (c) cell metabolism and catabolism, (d) cell transport, (e) cell structure organization and (f) organ/system-specific processes. This review aims to increase the knowledge on the mechanisms underlying the co-occurrence of tooth agenesis and orofacial clefts, to pave the way for improving targeted (prenatal) molecular diagnosis and finally to reflect on therapeutic or ultimately preventive strategies for these disabling conditions in the future.
2016
Phan, M.; Conte, F.; Khandelwal, K. D.; Ockeloen, C. W.; Bartzela, T.; Kleefstra, T.; van Bokhoven, H.; Rubini, Michele; Zhou, H.; Carels, C. E. L.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2356375
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