RESUMO
Inherited disorders of elastic tissue represent a complex and heterogeneous group of diseases, characterized often by sagging skin and occasionally by life-threatening visceral complications. In the present study, we report on an autosomal-recessive disorder that we have termed MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis). The disorder was mapped to chromosome 20p11.21-p11.23, and a homozygous frameshift mutation in RIN2 was found to segregate with the disease phenotype in a large consanguineous kindred. The mutation identified results in decreased expression of RIN2, a ubiquitously expressed protein that interacts with Rab5 and is involved in the regulation of endocytic trafficking. RIN2 deficiency was found to be associated with paucity of dermal microfibrils and deficiency of fibulin-5, which may underlie the abnormal skin phenotype displayed by the patients.
Assuntos
Alopecia/genética , Cútis Laxa/genética , Fatores de Troca do Nucleotídeo Guanina/deficiência , Escoliose/genética , Crânio/crescimento & desenvolvimento , Adolescente , Adulto , Proteínas de Transporte/genética , Estudos de Casos e Controles , Mapeamento Cromossômico , Cromossomos Humanos Par 20 , Consanguinidade , Cútis Laxa/metabolismo , Procedimentos Cirúrgicos Dermatológicos , Derme/metabolismo , Derme/patologia , Tecido Elástico/metabolismo , Tecido Elástico/ultraestrutura , Proteínas da Matriz Extracelular/metabolismo , Mutação da Fase de Leitura , Genes Recessivos , Fatores de Troca do Nucleotídeo Guanina/genética , Homozigoto , Humanos , Imuno-Histoquímica , Fenótipo , Radiografia , Pele/metabolismo , Pele/patologia , Crânio/diagnóstico por imagem , SíndromeRESUMO
A new group of genetic diseases characterized by defective glycoprotein biosynthesis was recently described. Transferrin isoelectric focusing enabled identification of several types of patients with congenital disorders of glycosylation (CDG). The authors report on the liver involvement in two siblings with CDG type Ix presenting with failure to thrive and hypertransaminasemia who developed cardiomyopathy. In the initially affected infant, liver biopsy at 13 months of age showed increased periportal cellularity, steatosis, and mild fibrosis. Ultrastructurally, the hepatocytes displayed numerous myelinosomes, mostly with a pericanalicular polarization. No myelinosomes were seen in the bile canaliculi, Kupffer cells, and sinusoidal lining cells. Focal large droplet steatosis was also noticed. These ultrastructural findings represent another diagnostic element in this heterogenic group of conditions. Electron microscopy can contribute to the elucidation of hypertransaminasemia and differentiate some types of CDG from other lysosomal diseases.