RESUMO
Described for the first time in 1971, Schimke immuno-osseous dysplasia (SIOD) is an autosomal-recessive multisystem disorder that is caused by bi-allelic mutations of SMARCAL1, which encodes a DNA annealing helicase. To define better the dental anomalies of SIOD, we reviewed the records from SIOD patients with identified bi-allelic SMARCAL1 mutations, and we found that 66.0% had microdontia, hypodontia, or malformed deciduous and permanent molars. Immunohistochemical analyses showed expression of SMARCAL1 in all developing teeth, raising the possibility that the malformations are cell-autonomous consequences of SMARCAL1 deficiency. We also found that stimulation of cultured skin fibroblasts from SIOD patients with the tooth morphogens WNT3A, BMP4, and TGFß1 identified altered transcriptional responses, raising the hypothesis that the dental malformations arise in part from altered responses to developmental morphogens. To the best of our knowledge, this is the first systematic study of the dental anomalies associated with SIOD.
Assuntos
Arteriosclerose/complicações , Síndromes de Imunodeficiência/complicações , Síndrome Nefrótica/complicações , Osteocondrodisplasias/complicações , Embolia Pulmonar/complicações , Anormalidades Dentárias/etiologia , Alelos , Anodontia/etiologia , Arteriosclerose/genética , Dente Pré-Molar/anormalidades , Proteína Morfogenética Óssea 4/análise , Técnicas de Cultura de Células , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , DNA Helicases/análise , DNA Helicases/genética , Fibroblastos/patologia , Humanos , Síndromes de Imunodeficiência/genética , Dente Molar/anormalidades , Mutação/genética , Síndrome Nefrótica/genética , Odontogênese/genética , Osteocondrodisplasias/genética , Doenças da Imunodeficiência Primária , Embolia Pulmonar/genética , Pele/citologia , Germe de Dente/patologia , Raiz Dentária/anormalidades , Dente Decíduo/anormalidades , Transcrição Gênica/genética , Fator de Crescimento Transformador beta1/análise , Proteína Wnt3A/análiseRESUMO
Preaxial polydactyly is a common limb malformation in humans with variable clinical expression. Different types of triphalangeal thumb-preaxial polydactyly phenotypes were mapped to the chromosome 7q36 region. We studied a large Turkish family of 69 individuals, of whom 22 individuals were affected. In all, 11 affected family members were clinically and radiologically evaluated. All affected individuals had a triphalangeal thumb and a preaxial (hypoplastic) extra digit bilaterally, with minimal intrafamilial variation. No feet involvement was observed. Linkage and haplotype analyses using 20 informative meioses confirmed the 7q36 region contained the LIMBR1 gene. Maximum logarithm of the odds (LOD) scores were obtained with DNA markers D7S550 and D7S2423. We have further identified a novel C to T alteration at position 4909 bp in the critical zone of polarizing activity regulatory sequence (ZRS) region, in the intron 5, of the LMBR1 gene. One affected male with homozygous status and no phenotypic difference from affected family members with heterozygous status represented the first homozygote case of the triphalangeal thumb-preaxial polydactyly phenotype.
Assuntos
Cromossomos Humanos Par 7/genética , Heterozigoto , Homozigoto , Polidactilia/genética , Sequência de Bases , Segregação de Cromossomos , Análise Mutacional de DNA , Feminino , Ligação Genética , Haplótipos , Humanos , Íntrons/genética , Masculino , Proteínas de Membrana/genética , Dados de Sequência Molecular , Linhagem , FenótipoRESUMO
We present a 30 week old male fetus who had a very interesting malformation complex which can not be explained by teratogenic or hereditary diseases. The aim of this paper is to discuss this complicated entity and compare it with other reported cases.
