Descrição:

Mutations in the anthrax toxin receptor 2 (ANTXR2) gene, also known as the capillary morphogenesis protein 2 (CMG2) gene, result in Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH), both of which are inherited as autosomal recessive traits. Although JHF and ISH share many clinical similarities, including papulonodular skin lesions, gingival hypertrophy, and flexion contractures, ISH usually has an earlier age at onset, a more painful and severe course, and often death in infancy from multisystem failure. Eighteen different mutations have been described in 22 families with JHF or ISH. Of these 18 mutations, 3 have been found in two kindreds and 1 (c.1073_1074insC) has been found in five kindreds. Objectives: To determine the ANTXR2 mutations in four unrelated Brazilian families segregating JHF, three of which were known to be consanguineous, ascertained from the central portion of Brazil. Methods: PCR amplification and direct sequencing of the ANTXR2 exons was performed. Intra- and intergenic microsatellite markers were genotyped for haplotype analysis. Results: Sequence analysis revealed that all affected individuals were homozygous for a single nucleotide deletion in exon 13 (c.1074delT). This mutation causes a frameshift and introduces a premature truncation site (p.K361fsX408). Haplotype analysis supported inheritance of the mutation from a common ancestor for all families. Conclusion: All families appear to have inherited the c.1074delT mutation from a common ancestor. The c.1074delT mutation has been previously reported in a Kuwaiti family with ISH. The difference in phenotype may be related to modifying genes or to polymorphisms within the ANTXR2 gene. The Brazilian JHF patients were also homozygous for an Ala357Pro missense alteration that was not present in the Kuwati family. Thus, the c.1074delT mutation appears to have arisen at least twice. The c.1074 region may represent a mutational hotspot as 3 of the 18 known mutations occur at this region.

Coordenador:

Profa. Dra. Debora Pallos (curriculo LATTES)

Financiador:

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Modalidade: PAEX- Auxílio Programa de Apoio à Eventos no Exterior

Edital:Processo 4243-05-6

Ano: 2006

Valor: US$1.200,00

Publicações ligadas ao projeto:

PALLOS, D. ; HART, Patricia Suzanne ; ACEVEDO, Ana Carolina ; RAMASWAMI, M D ; MESTRINHO, Heliana ; SPECK, Carlos ; HART, Thomas Charles . Juvenile Hyaline Fibromatosis Due to Founder Mutation in Brazil.. In: IADR, 2006, Orlando. Journal of Dental Research, 2006