Clinical study and some molecular features of Mexican patients with syndromic craniosynostosis.

Abstract

BACKGROUND:

Craniosynostosis is one of the major genetic disorders affecting 1 in 2,100-2,500 live newborn children. Environmental and genetic factors are involved in the manifestation of this disease. The suggested genetic causes of craniosynostosis are pathogenic variants in FGFR1, FGFR2, FGFR3, and TWIST1 genes.

METHODS:

In order to describe their major clinical characteristics and the presence of pathogenic variants, a sample of 36 Mexican patients with craniosynostosis diagnosed as: Crouzon (OMIM 123,500), Pfeiffer (OMIM 101,600), Apert (OMIM 101,200), Saethre-Chotzen (OMIM 101,400), and Muenke (OMIM 602,849) was analyzed.

RESULTS:

In addition to craniosynostosis, most of the patients presented hypertelorism, midface hypoplasia, and abnormalities in hands and feet. To detect the pathogenic variants p.Pro252Arg FGFR1 (OMIM 136,350), p.Ser252Trp, p.Pro253Arg FGFR2 (OMIM 176,943), p.Pro250Arg, FGFR3 (OMIM 134,934), and p.Gln119Pro TWIST1 (OMIM 601,622), PCR amplification and restriction enzyme digestion were performed. Four and two patients with Apert presented the pathogenic variants p.Ser252Trp and p.Pro253Arg in FGFR2, respectively (with a frequency of 11.1% and 5.5%). The p.Pro250Arg pathogenic variant of FGFR3 was found in a patient with Muenke (with a frequency of 2.8%). The above percentages were calculated with the total number of patients.

CONCLUSION:

The contribution of this work is discreet, since only 4 genes were analyzed and sample size is small. However, this strategy could be improved by sequencing the FGFR1, FGFR2, FGFR3, and TWIST1 genes, to determine different pathogenic variants. On the other hand, it would be important to include other genes, such as TCF12 (OMIM 600,480), MSX2 (OMIM 123,101), RAB23 (OMIM 606,144), and EFNB1 (OMIM 300,035), to determine their participation in craniosynostosis in the Mexican population.

• Authors: Aurora Ibarra-Arce, Manuel Almaraz-Salinas, Víctor Martínez-Rosas, Gabriela Ortiz de Zárate-Alarcón, Laura Flores-Peña, Mirza Romero-Valdovinos, Angélica Olivo-Díaz
• Journal: Molecular genetics & genomic medicine (Mol Genet Genomic Med) Vol. 8 Issue 8 Pg. e1266 (08 2020) ISSN: 2324-9269 [Electronic] United States
• PMID: 32510873 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

Chemical References

• Nuclear Proteins
• Receptors, Fibroblast Growth Factor
• TWIST1 protein, human
• Twist-Related Protein 1

Topics

• Adult
• Child
• Child, Preschool
• Craniosynostoses (genetics, pathology)
• Female
• Gene Frequency
• Humans
• Infant
• Male
• Mexico
• Mutation, Missense
• Nuclear Proteins (genetics)
• Phenotype
• Receptors, Fibroblast Growth Factor (genetics)
• Twist-Related Protein 1 (genetics)