RESUMO
The dysfunction of microtubules (α/ß-tubulin polymers) underlies a wide range of nervous system genetic abnormalities. Defects in TBCD, a tubulin-folding cofactor, cause diseases highlighted with early-onset encephalopathy with or without neurodegeneration, intellectual disability, seizures, microcephaly and tetraparaperesis. Utilizing various molecular methods, we describe nine patients from four unrelated families with two novel exon 18 variants in TBCD exhibiting the typical neurological phenotype of the disease. Interestingly, all the investigated patients had previously unreported hematological findings in the form of neutropenia and mild degree of anemia and thrombocytopenia. In addition to delineating the neurological phenotype in several patients with TBCD variants, our study stresses on the new association of neutropenia, in particular, with the disease.
Assuntos
Encefalopatias/sangue , Encefalopatias/genética , Proteínas Associadas aos Microtúbulos/genética , Mutação de Sentido Incorreto , Adulto , Anemia/etiologia , Encefalopatias/complicações , Encefalopatias/diagnóstico por imagem , Criança , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Neutropenia/etiologia , Linhagem , Trombocitopenia/etiologia , Adulto JovemRESUMO
Septic arthritis is truly an emergency condition that needs an early diagnosis by appropriate clinical examination/judgment and using fast, available, and accurate radiological imaging and laboratory septic workup. Early diagnosis may prevent complications that may otherwise lead to the patient's disability.
Assuntos
Fissura Palatina/genética , Colágeno Tipo II/genética , Nanismo/genética , Doença da Membrana Hialina/genética , Mutação , Sítios de Splice de RNA/genética , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Pré-Escolar , Fissura Palatina/patologia , Doenças do Colágeno , Análise Mutacional de DNA , Nanismo/patologia , Éxons , Face/anormalidades , Face/patologia , Feminino , Testes Genéticos/métodos , Genoma Humano , Humanos , Doença da Membrana Hialina/patologia , Osteocondrodisplasias , Exame FísicoRESUMO
BACKGROUND: Dyggve--Melchior--Clausen syndrome (DMC) is a chondrodysplasia that bears significant phenotypic resemblance to mucopolysaccharidosis type IV (Morquio disease). Autosomal recessive mutations in DYM are known to cause this disease through its role in Golgi organisation and intracellular traffic, but genetic heterogeneity is suspected. METHODS: A family with DMC and normal intellectual development underwent clinical evaluation followed by autozygosity mapping and exome sequencing. Immunoblot and immunofluorescence analyses were performed to characterise the effect of the mutation. RESULTS: This multiplex consanguineous family links to a novel locus on 4q31.1. Exome sequencing revealed a missense mutation in RAB33B, which encodes a Rab protein with an established role in retrograde Golgi traffic. The mutation qualitatively replaces the invariant lysine residue in the guanine nucleotide-binding domain of this small GTPase protein and leads to marked protein deficiency, making it the likely causative mutation of DMC in this family. CONCLUSION: This study identifies a new DMC gene and highlights the role of intracellular traffic in the pathogenesis of this disease.
