A new genetic cause of orofaciodigital syndrome identified

Orofaciodigital syndrome is characterized by anatomical alterations of various structures of the oral cavity (mainly tongue and teeth), anomalies in the number and appearance of the digits of the hands and feet, and the presence of distinctive facial features. This syndrome is genetically heterogeneous and is caused by mutations in several genes related to the primary cilium, an organelle specialized in the reception and transduction of extracellular signals.

The protein encoded by the SCNM1 gene (sodium channel modifier 1) is part of the minor spliceosome, which is a ribonucleoprotein complex that excises a special type of introns called minorities, or U12 introns, during the processing of RNA molecules. messenger (mRNA).

Using various cellular models, the authors of a new study show that the lack of function of SCNM1 causes alterations in the mRNA of a set of genes carrying U12 introns, some of which are related to the primary cilium. Consequently, SCNM1-deficient cells develop longer primary cilia, and exhibit less efficient functioning of the hedgehog signaling pathway, which is associated with abnormalities of embryonic development.

In summary, the new study has shown that a previously unknown cause of orofaciodigital syndrome is due to loss-of-function mutations in the SCNM1 gene.

The study was carried out by an international team coordinated by Víctor Luis Ruiz-Pérez, from the Rare Diseases Network Biomedical Research Center (CIBERER), as well as from the Alberto-Sols Biomedical Research Institute, a center attached to the Higher Council for Scientific Research ( CSIC) and the Autonomous University of Madrid (UAM), in Spain all these entities.

From left to right, Marina Leonor, Carmen Lisset, Víctor Luis Ruiz-Perez, Asier Iturrate and Julián Nevado, from the research team. (Photo: CIBERER)

Scientists from the La Paz Hospital, the CSS Mendel Institute in Rome, the University of Istanbul, the University of Alexandria and the Cairo National Research Center have also participated in this study.

The study is titled “Mutations in SCNM1 cause orofaciodigital syndrome due to minor intron splicing defects affecting primary cilia.” And it has been published in the academic journal AJHG. (Source: CIBERER)