RESUMEN
BACKGROUND: Raine syndrome (RS) is a rare autosomal recessive bone dysplasia typified by osteosclerosis and dysmorphic facies due to FAM20C mutations. Initially reported as lethal in infancy, survival is possible into adulthood. We describe the molecular analysis and clinical phenotypes of five individuals from two consanguineous Brazilian families with attenuated Raine Syndrome with previously unreported features. METHODS: The medical and dental clinical records were reviewed. Extracted deciduous and permanent teeth as well as oral soft tissues were analysed. Whole exome sequencing was undertaken and FAM20C cDNA sequenced in family 1. RESULTS: Family 1 included 3 siblings with hypoplastic Amelogenesis Imperfecta (AI) (inherited abnormal dental enamel formation). Mild facial dysmorphism was noted in the absence of other obvious skeletal or growth abnormalities. A mild hypophosphataemia and soft tissue ectopic mineralization were present. A homozygous FAM20C donor splice site mutation (c.784 + 5 g > c) was identified which led to abnormal cDNA sequence. Family 2 included 2 siblings with hypoplastic AI and tooth dentine abnormalities as part of a more obvious syndrome with facial dysmorphism. There was hypophosphataemia, soft tissue ectopic mineralization, but no osteosclerosis. A homozygous missense mutation in FAM20C (c.1487C > T; p.P496L) was identified. CONCLUSIONS: The clinical phenotype of non-lethal Raine Syndrome is more variable, including between affected siblings, than previously described and an adverse impact on bone growth and health may not be a prominent feature. By contrast, a profound failure of dental enamel formation leading to a distinctive hypoplastic AI in all teeth should alert clinicians to the possibility of FAM20C mutations.
Asunto(s)
Anomalías Múltiples/genética , Quinasa de la Caseína I/genética , Fisura del Paladar/genética , Exoftalmia/genética , Proteínas de la Matriz Extracelular/genética , Microcefalia/genética , Anomalías de la Boca/complicaciones , Mutación , Osteosclerosis/genética , Linaje , Fenotipo , Anomalías Dentarias/complicaciones , Adolescente , Secuencia de Bases , Niño , Preescolar , Fisura del Paladar/complicaciones , Exoftalmia/complicaciones , Femenino , Humanos , Masculino , Microcefalia/complicaciones , Osteosclerosis/complicaciones , Adulto JovenRESUMEN
OBJECTIVES: To describe 3 children with mutations in a Meckel syndrome gene (MKS3), with features of autosomal recessive polycystic kidney disease (ARPKD), nephronophthisis, and Joubert syndrome (JS). STUDY DESIGN: Biochemical evaluations, magnetic resonance and ultrasound imaging, electroretinograms, IQ testing, and sequence analysis of the PKHD1 and MKS3 genes were performed. Functional consequences of the MKS3 mutations were evaluated by cDNA sequencing and transfection studies with constructs of meckelin, the protein product of MKS3. RESULTS: These 3 children with MKS3 mutations had features typical of ARPKD, that is, enlarged, diffusely microcystic kidneys and early-onset severe hypertension. They also exhibited early-onset chronic anemia, a feature of nephronophthisis, and speech and oculomotor apraxia, suggestive of JS. Magnetic resonance imaging of the brain, originally interpreted as normal, revealed midbrain and cerebellar abnormalities in the spectrum of the "molar tooth sign" that characterizes JS. CONCLUSIONS: These findings expand the phenotypes associated with MKS3 mutations. MKS3-related ciliopathies should be considered in patients with an ARPKD-like phenotype, especially in the presence of speech and oculomotor apraxia. In such patients, careful expert evaluation of the brain images can be beneficial because the brain malformations can be subtle.
Asunto(s)
Anomalías Múltiples/genética , Trastornos de la Motilidad Ciliar/genética , Proteínas de la Membrana/genética , Mutación , Riñón Poliquístico Autosómico Recesivo/genética , Anomalías Múltiples/diagnóstico , Encéfalo/anomalías , Encéfalo/patología , Niño , Trastornos de la Motilidad Ciliar/diagnóstico , Femenino , Humanos , Riñón/anomalías , Riñón/diagnóstico por imagen , Riñón/patología , Hígado/anomalías , Hígado/patología , Imagen por Resonancia Magnética , Masculino , Riñón Poliquístico Autosómico Recesivo/diagnóstico , Hermanos , Síndrome , UltrasonografíaRESUMEN
Estudou-se a taxa de dessecaçäo das fezes de triatomíneos à temperatura ambiente e diferentes umidades relativaws e à temperatura média da pele humana (33-C). O tempo necessário para evaporar a água contida nas fezes de barbeiro é inversamente proporcional ao déficit de saturaçäo atmosférica e é acelerado a temperaturas mais altas. Estudou-se a motilidade dos flagelados fecais diretamente ao microscópio e a infectividade dos mesmos após introduçäo na cavidade peritoneal de camundongos. A baixa umidade de ambas, motilidade e infectividade, foram perdidas antes de 30 minutos. Em altas umidades esses parâmetros foram preservados, em grau variado, por mais de 30 minutos. A 33-C, 100% dos camundongos foram infectados depois de 15 minutos, mas somente 3,3% após 30 minutos de exposiçäo. As condiçöes ambientais no interior de uma casa em Mambaí variaram acentuadamente no período de estudo. Entretanto, foram geralmente similares áqueles observados experimentalmente em laboratório