RESUMEN
The genotype-phenotype relationship of compound heterozygous protein S-deficiency in a 7-year-old girl with reduced protein S-levels and a severe cerebral sinovenous thrombosis is illustrated. In this patient we identified a novel deletion in the protein S-gene causing a compound heterozygous state and subsequently a symptomatic protein S-deficiency. In case of thrombosis analysis of protein S is recommended. Low levels of protein S should be further investigated by molecular diagnostics.
Asunto(s)
Análisis Mutacional de ADN , Tamización de Portadores Genéticos , Genotipo , Fenotipo , Deficiencia de Proteína S/genética , Trombosis de los Senos Intracraneales/genética , Anticoagulantes/uso terapéutico , Infarto Cerebral/diagnóstico , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/genética , Niño , Deleción Cromosómica , Epilepsia Generalizada/tratamiento farmacológico , Epilepsia Generalizada/etiología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Intracraneal/diagnóstico , Hipertensión Intracraneal/tratamiento farmacológico , Hipertensión Intracraneal/genética , Angiografía por Resonancia Magnética , Mutación Missense/genética , Deficiencia de Proteína S/diagnóstico , Deficiencia de Proteína S/tratamiento farmacológico , Trombosis de los Senos Intracraneales/diagnóstico , Trombosis de los Senos Intracraneales/tratamiento farmacológico , Enfermedades Talámicas/diagnóstico , Enfermedades Talámicas/tratamiento farmacológico , Enfermedades Talámicas/genéticaRESUMEN
BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder causing oculocutaneous albinism, bleeding disorder and ceroid lipofuscinosis. Platelets from HPS patients are characterized by the absence of dense (delta)-bodies. There are eight known human HPS GENES (HPS1-HPS8), each leading to a particular clinical HPS subtype. Restrictive lung disease, granulomatous colitis and cardiomyopathy have been described in HPS1 patients. PATIENTS: We identified HPS1 in Russian and in German siblings. All four patients show a typical HPS phenotype. The two older Russian patients demonstrate excessive bleeding after tooth extractions, recurrent epistaxis and hematomas. The two younger German patients suffer only from hematomas, so far. METHODS/RESULTS: Patients' platelets showed severe pathological agglutination/aggregation. Flow cytometry analysis demonstrated absence of platelet delta-granule secretion. Three different mutations in the HPS1 gene were found in the two families. Two mutations, p.H119delC and p.Q397delC identified in the Russian siblings had been previously described. The German siblings presented with a novel frameshift mutation (p.Q32_S33delCAGT) and the known p.Q397delC mutation. CONCLUSION: Patients with oculocutaneous albinism should be investigated for increased clinical bleeding symptoms. In case of increased bleeding symptoms, analyses of primary hemostasis should be initiated to confirm HPS. Molecular genetic investigations should be performed to distinguish the different subtypes of HPS which is important for therapy and prognosis.
Asunto(s)
Análisis Mutacional de ADN , Tamización de Portadores Genéticos , Genotipo , Síndrome de Hermanski-Pudlak/genética , Adulto , Edad de Inicio , Alelos , Tiempo de Sangría , Niño , Preescolar , Deleción Cromosómica , Codón sin Sentido/genética , Exones , Femenino , Mutación del Sistema de Lectura/genética , Síndrome de Hermanski-Pudlak/sangre , Humanos , Masculino , Linaje , Fenotipo , Pruebas de Función Plaquetaria , Análisis de Secuencia de ADN , Adulto JovenAsunto(s)
Trastornos Generalizados del Desarrollo Infantil/genética , Hemofilia A/genética , Discapacidad Intelectual/genética , Trastornos del Desarrollo del Lenguaje/genética , Trastornos Psicomotores/genética , Trastornos Generalizados del Desarrollo Infantil/diagnóstico , Preescolar , Duplicación Cromosómica , Cromosomas Humanos X/genética , Consanguinidad , Análisis Mutacional de ADN , Factor VIII/genética , Estudios de Seguimiento , Hemofilia A/diagnóstico , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Trastornos del Desarrollo del Lenguaje/diagnóstico , Masculino , Mutación Missense , Análisis de Secuencia por Matrices de Oligonucleótidos , Linaje , Trastornos Psicomotores/diagnóstico , Aberraciones Cromosómicas SexualesAsunto(s)
Hemofilia A/complicaciones , Hemofilia A/diagnóstico , Degeneración Hepatolenticular/complicaciones , Degeneración Hepatolenticular/diagnóstico , Adenosina Trifosfatasas/genética , Proteínas de Transporte de Catión/genética , Deleción Cromosómica , Inversión Cromosómica , ATPasas Transportadoras de Cobre , Análisis Mutacional de ADN , Diagnóstico Precoz , Factor VIII/genética , Factor VIII/uso terapéutico , Tamización de Portadores Genéticos , Hemofilia A/genética , Hemofilia A/terapia , Degeneración Hepatolenticular/genética , Degeneración Hepatolenticular/terapia , Humanos , Intrones , Pruebas de Función Hepática , Masculino , Penicilamina/uso terapéutico , Ultrasonografía , Vitamina B 6/uso terapéuticoAsunto(s)
Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome de Down/complicaciones , Síndrome de Down/diagnóstico , Enoxaparina/uso terapéutico , Venas Renales , Tromboflebitis/diagnóstico , Tromboflebitis/tratamiento farmacológico , Trombosis/diagnóstico , Trombosis/tratamiento farmacológico , Vena Cava Inferior , Adolescente , Anticuerpos Antifosfolípidos/sangre , Anticoagulantes/efectos adversos , Antitrombinas/efectos adversos , Antitrombinas/uso terapéutico , Diagnóstico Diferencial , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Enoxaparina/efectos adversos , Femenino , Hirudinas/efectos adversos , Humanos , Inmunoglobulina M/sangre , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , beta 2 Glicoproteína I/inmunologíaRESUMEN
The presence and role of septin proteins in yeast is well documented, but there is a growing appreciation for this family of proteins beyond yeast and extending to human cells. In this report we present the characterization and comparison of two highly similar human septin genes, PNUTL1 and PNUTL2. We compare the exon/intron structure of both genes, the steady-state mRNA levels in tumor cell lines and adult organs, the conceptual translation products from alternatively processed mRNAs and the development of specific immunologic reagents distinguishing either PNUTL1 or PNUTL2. The results illustrate a remarkable similarity between the two genes and their protein products while identifying specific differences in mRNA expression patterns. A summary of the described functional roles for mammalian septins is discussed along with an attempt to assimilate the alternative nomenclature existing for the same human septins, such as references to PNUTL1 and PNUTL2 as hCDCrel-1 and hCDCrel-2, respectively. The characterization of PNUTL1 and PNUTL2 represents a fundamental step in completing the characterization of the entire family of human septin genes.