New Genetic Variants of RUNX2 in Mexican Families Cause Cleidocranial Dysplasia

• Published in: Biology (Basel, Switzerland) Vol. 13; no. 3; p. 173
• Main Authors: Toral López, Jaime, Gómez Martinez, Sandra, Rivera Vega, María Del Refugio, Hernández-Zamora, Edgar, Cuevas Covarrubias, Sergio, Ibarra Castrejón, Belem Arely, González Huerta, Luz María
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.03.2024; MDPI
• Subjects: Amino acids; Aplasia; Bioinformatics; Bone dysplasia; Brief Report; Calvaria; Cataracts; Cbfa-1 protein; CCD; Cell differentiation; Clavicle; cleidocranial dysplasia; Comparative analysis; Craniofacial syndromes; Energy; Finger; Genetic counseling; Genetic diversity; Genotype & phenotype; Hypoplasia; Mutation; novel mutations; Phenotypes; Polypeptides; Protein structure; Proteins; Rare diseases; Runt-related transcription factor 2 gene; RUNX2 gene; Skeleton; Skull; Structure-function relationships; Transcription factors; Vertebrae; Runt-related transcription factor 2 gene; RUNX2 gene; CCD; novel mutations; cleidocranial dysplasia
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology13030173

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by persistent open skull sutures with bulging calvaria, hypoplasia, or aplasia of clavicles permitting abnormal opposition of the shoulders; wide public symphysis; short middle phalanx of the fifth fingers; and vertebral, craniofacial, and dental anomalies. It is a rare disease, with a prevalence of 1-9/1,000,000, high penetrance, and variable expression. The gene responsible for CCD is the Runt-related transcription factor 2 ( ) gene. We characterize the clinical, genetic, and bioinformatic results of four CCD cases: two cases within Mexican families with six affected members, nine asymptomatic individuals, and two sporadic cases with CCD, with one hundred healthy controls. Genomic DNA analyses of the gene were performed for Sanger sequencing. Bioinformatics tools were used to predict the function, stability, and structural changes of the mutated RUNX2 proteins. Three novel heterozygous mutations (c.651_652delTA; c.538_539delinsCA; c.662T>A) and a previously reported mutation (c.674G>A) were detected. In silico analysis showed that all mutations had functional, stability-related, and structural alterations in the RUNX2 protein. Our results show novel mutations that enrich the pool of gene mutations with CCD. Moreover, the proband 1 presented clinical data not previously reported that could represent an expanded phenotype of severe expression.