RESUMO
RATIONALE: Ectrodactyly ectodermal dysplasia-cleft lip/palate (EEC) syndrome, limb-mammary syndrome (LMS), and acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome are caused by a TP63 gene disorder and have similar features. In the present article, a R319H mutation in TP63 is reported, and the correlation between genotype and phenotype is discussed based on the current case and previous literature. PATIENT CONCERNS: A 13-year-old Japanese boy had ectrodactyly in the right hand and left foot and syndactyly in the left and right foot, and tooth shape abnormalities. DIAGNOSES: Peripheral blood samples were obtained, and mutation analysis was performed. A heterozygous G>A transition at cDNA position 956 of the TP63 gene was found. The patient was diagnosed with ELA (EEC/LM/ADULT) syndrome based on his clinical features and mutation analysis results. INTERVENTIONS: The patient underwent surgery to correct the left foot malformation at 1 year of age and the right foot syndactyly at 11 years of age. OUTCOMES: No complications were observed after the first and second operations. He can walk comfortably after them, and no additional interventions will be planned in him. We continued to follow up with him up to the present. LESSONS: The concept of ELA syndrome, which is the original concept of combining 3 syndromes (EEC syndrome/LMS/ADULT syndrome) into a unique clinical entity, can help clinicians to better understand TP63-related syndromes and improve the differential diagnosis of these syndromes.
Assuntos
Anodontia/sangue , Mama/anormalidades , Fissura Palatina/sangue , Displasia Ectodérmica/sangue , Dedos/anormalidades , Deformidades Congênitas da Mão/sangue , Obstrução dos Ductos Lacrimais/sangue , Deformidades Congênitas dos Membros/sangue , Unhas Malformadas/sangue , Transtornos da Pigmentação/sangue , Fatores de Transcrição/análise , Proteínas Supressoras de Tumor/análise , Adolescente , Anodontia/genética , Fissura Palatina/genética , Displasia Ectodérmica/genética , Deformidades Congênitas da Mão/genética , Humanos , Japão , Obstrução dos Ductos Lacrimais/genética , Deformidades Congênitas dos Membros/genética , Masculino , Mutação/genética , Unhas Malformadas/genética , Transtornos da Pigmentação/genética , Fatores de Transcrição/sangue , Proteínas Supressoras de Tumor/sangueRESUMO
Lubricin, encoded by the gene PRG4, is the principal lubricant in articulating joints. We immunized mice genetically deficient for lubricin (Prg4-/-) with purified human lubricin, and generated several mAbs. We determined each mAb's binding epitope, sensitivity, and specificity using biologic samples and recombinant lubricin sub-domains, and we also developed a competition ELISA assay to measure lubricin in synovial fluid and blood. We found the mAbs all recognized epitopes containing O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT. By western blot, the mAbs detected lubricin in 1 µl of synovial fluid from several animal species, including human. The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. The competition ELISA detected lubricin in blood samples from healthy individuals but not from patients with CACP, indicating blood can be used in a diagnostic test for patients suspected of having CACP. Lubricin epitopes in blood do not represent degradation fragments from synovial fluid. Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid.
Assuntos
Anticorpos Monoclonais/imunologia , Artropatia Neurogênica/sangue , Coxa Vara/sangue , Ensaio de Imunoadsorção Enzimática , Glicoproteínas/deficiência , Glicoproteínas/imunologia , Deformidades Congênitas da Mão/sangue , Articulações/metabolismo , Sinovite/sangue , Adulto , Idoso , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Estudos de Casos e Controles , Epitopos/química , Epitopos/imunologia , Feminino , Glicoproteínas/sangue , Glicoproteínas/genética , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Oligopeptídeos/química , Oligossacarídeos/química , Líquido Sinovial/metabolismoRESUMO
Shortening of the tubular bones of the hands and feet with cone shaped epiphyses is known as peripheral dysostosis and is common to several syndromes including acrodysostosis and Albright's hereditary osteodystrophy (AHO). The underlying defect in AHO is known to be a reduction in bioactivity of the alpha subunit of the signal transducing protein, Gs, and heterozygous deactivating mutations have been shown in the Gs alpha gene. Because of additional overlapping clinical and radiological features it has been suggested that acrodysostosis and AHO represent poles of a single diagnostic spectrum. We have measured Gs alpha bioactivity in two unrelated patients with a clinical diagnosis of acrodysostosis and found both to be normal. Mutation analysis of the Gs alpha gene showed no sequence variation in 12 of the 13 exons examined. These results indicate that, at least in a proportion of patients with acrodysostosis, the condition is aetiologically distinct from AHO.