Assuntos
Transtornos Plaquetários/genética , Predisposição Genética para Doença , Perda Auditiva Neurossensorial/diagnóstico , Cadeias Pesadas de Miosina/genética , Agregação Plaquetária/genética , Glândulas Sudoríparas/anormalidades , Trombocitopenia/congênito , Adolescente , Criança , Elastina/sangue , Feminino , Mutação em Linhagem Germinativa , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , Linhagem , Doenças Raras , Estudos de Amostragem , Síndrome , Trombocitopenia/diagnóstico , Trombocitopenia/genética , Adulto JovemAssuntos
Hiperceratose Epidermolítica/genética , Queratina-10/genética , Mutação de Sentido Incorreto/genética , Pré-Escolar , Feminino , Heterozigoto , Humanos , Hiperceratose Epidermolítica/tratamento farmacológico , Hiperceratose Epidermolítica/patologia , Indicadores e Reagentes/administração & dosagem , Indicadores e Reagentes/uso terapêutico , Pomadas/administração & dosagem , Pomadas/uso terapêutico , Fenótipo , Permanganato de Potássio/administração & dosagem , Permanganato de Potássio/uso terapêutico , Anormalidades da Pele/genética , Anormalidades da Pele/patologia , Resultado do Tratamento , Ureia/administração & dosagem , Ureia/uso terapêuticoAssuntos
Síndrome de Loeys-Dietz/genética , Osteoporose/genética , Deleção de Sequência , Fator de Crescimento Transformador beta2/genética , Adulto , Criança , Feminino , Humanos , Síndrome de Loeys-Dietz/complicações , Síndrome de Loeys-Dietz/diagnóstico , Masculino , Osteoporose/complicações , Osteoporose/diagnóstico , Linhagem , PrognósticoRESUMO
Cartilage-hair hypoplasia is a rare, autosomal recessive skeletal dysplasia, caused by mutations in the RMRP gene. The skeletal abnormalities include irregular metaphyses and cone shaped epiphyses of the hands. Molecular diagnosis confirmed two novel RMRP mutations in a compound heterozygous state in two siblings with this condition.
Assuntos
Doença de Hirschsprung/genética , Síndromes de Imunodeficiência/genética , Osteocondrodisplasias/congênito , RNA não Traduzido/genética , Adolescente , Sequência de Bases , Criança , Consanguinidade , Análise Mutacional de DNA , Feminino , Triagem de Portadores Genéticos , Cabelo/anormalidades , Doença de Hirschsprung/diagnóstico , Humanos , Síndromes de Imunodeficiência/diagnóstico , Masculino , Dados de Sequência Molecular , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Doenças da Imunodeficiência Primária , RNA Longo não Codificante , Alinhamento de SequênciaRESUMO
We recently reported on the deficiency of carbohydrate sulfotransferase 3 (CHST3; chondroitin-6-sulfotransferase) in six subjects diagnosed with recessive Larsen syndrome or humero-spinal dysostosis [Hermanns et al. (2008); Am J Hum Genet 82:1368-1374]. Since then, we have identified 17 additional families with CHST3 mutations and we report here on a series of 24 patients in 23 families. The diagnostic hypothesis prior to molecular analysis had been: Larsen syndrome (15 families), humero-spinal dysostosis (four cases), chondrodysplasia with multiple dislocations (CDMD "Megarbane type"; two cases), Desbuquois syndrome (one case), and spondylo-epiphyseal dysplasia (one case). In spite of the different diagnostic labels, the clinical features in these patients were similar and included dislocation of the knees and/or hips at birth, clubfoot, elbow joint dysplasia with subluxation and limited extension, short stature, and progressive kyphosis developing in late childhood. The most useful radiographic clues were the changes of the lumbar vertebrae. Twenty-four different CHST3 mutations were identified; 16 patients had homozygous mutations. We conclude that CHST3 deficiency presents at birth with congenital dislocations of knees, hips, and elbows, and is often diagnosed initially as Larsen syndrome, humero-spinal dysostosis, or chondrodysplasia with dislocations. The incidence of CHST3 deficiency seems to be higher than assumed so far. The clinical and radiographic pattern (joint dislocations, vertebral changes, normal carpal age, lack of facial flattening, and recessive inheritance) is characteristic and distinguishes CHST3 deficiency from other disorders with congenital dislocations such as filamin B-associated dominant Larsen syndrome and Desbuquois syndrome.
Assuntos
Luxações Articulares/genética , Coluna Vertebral/anormalidades , Sulfotransferases/deficiência , Família , Feminino , Homozigoto , Humanos , Lactente , Luxações Articulares/diagnóstico , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/metabolismo , Masculino , Mutação , Polimorfismo de Nucleotídeo Único , Radiografia , Pele/metabolismo , Sulfotransferases/genética , Carboidrato SulfotransferasesRESUMO
Deficiency of carbohydrate sulfotransferase 3 (CHST3; also known as chondroitin-6-sulfotransferase) has been reported in a single kindred so far and in association with a phenotype of severe chondrodysplasia with progressive spinal involvement. We report eight CHST3 mutations in six unrelated individuals who presented at birth with congenital joint dislocations. These patients had been given a diagnosis of either Larsen syndrome (three individuals) or humero-spinal dysostosis (three individuals), and their clinical features included congenital dislocation of the knees, elbow joint dysplasia with subluxation and limited extension, hip dysplasia or dislocation, clubfoot, short stature, and kyphoscoliosis developing in late childhood. Analysis of chondroitin sulfate proteoglycans in dermal fibroblasts showed markedly decreased 6-O-sulfation but enhanced 4-O-sulfation, confirming functional impairment of CHST3 and distinguishing them from diastrophic dysplasia sulphate transporter (DTDST)-deficient cells. These observations provide a molecular basis for recessive Larsen syndrome and indicate that recessive Larsen syndrome, humero-spinal dysostosis, and spondyloepiphyseal dysplasia Omani type form a phenotypic spectrum.