RESUMEN
Autoimmune lymphoproliferative syndrome (ALPS) is characterized by chronic, histologically benign splenomegaly and generalized lymphadenopathy, hypergammaglobulinemia, and autoantibody formation. ALPS has been attributed to defective programmed cell death of lymphocytes, most often arising as a result of mutations in the gene encoding the lymphocyte apoptosis receptor Fas/APO-l/CD95. We identified a novel mutation in the intracellular apoptosis signaling domain of Fas in 11 members of a family, individual members of which have been monitored for up to 25 years, with 1 or more features of ALPS. This study of a large number of family members carrying the same Fas defect demonstrates that ALPS is inherited in an autosomal dominant fashion but with a high degree of variability in clinical expression. Although 1 affected individual died of postsplenectomy sepsis and 1 has been treated for lymphoma, the Fas mutation in this family has been compatible with a healthy adulthood, as clinical features of ALPS have receded with increasing age.
Asunto(s)
Apoptosis/genética , Enfermedades Autoinmunes/genética , Trastornos Linfoproliferativos/genética , Receptores del Factor de Necrosis Tumoral/genética , Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/inmunología , Enfermedades Autoinmunes/inmunología , Relación CD4-CD8 , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Tamización de Portadores Genéticos , Humanos , Trastornos Linfoproliferativos/inmunología , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Pronóstico , Receptor fasRESUMEN
Hereditary medullary thyroid carcinoma is inherited as an autosomal dominant trait; at birth each child of an affected parent has a 50% chance of developing the disease. Measurement of plasma calcitonin concentrations after provocative calcium or pentagastrin stimulation has proved useful in the early diagnosis of this disease. To determine the age-related risk of conversion from a negative to a positive provocative test, 445 members of 11 kindreds were studied with sequential tests. Of 159 family members with a 50% risk at birth of developing medullary thyroid carcinoma 38 converted from a negative to a positive test result (mean age of conversion was 15 years). By means of methods previously described for determining the age-related probability for developing Huntington chorea, we present a method for determining the probability of development of medullary thyroid carcinoma. An individual at risk whose test result was negative had the following probability of converting to a positive test result at a later date: age (years)/probability, 0/0.5; 5/0.49; 10/0.41; 15/0.25; 20/0.16; 25/0.10, 30/0.05; and 35/0. We conclude that hereditary medullary thyroid carcinoma is regularly detectable in the pediatric age group and that screening should begin by age 5 years and be continued at regular intervals until age 35.
Asunto(s)
Carcinoma/genética , Neoplasias de la Tiroides/genética , Adolescente , Adulto , Factores de Edad , Calcitonina/sangre , Carcinoma/diagnóstico , Niño , Preescolar , Asesoramiento Genético , Humanos , Estudios Prospectivos , Riesgo , Neoplasias de la Tiroides/diagnósticoRESUMEN
An unusual spectrum of craniofacial and foot abnormalities has been detected within a large midwestern Amish kindred. Enlarged great toes and craniofacial abnormalities suggested Pfeiffer acrocephalosynadactyly type V; however, thumb abnormalities were not present. Eighty-eight affected individuals were observed and another 50 were reliably reported to be affected. An autosomal dominant inheritance pattern was observed associated with variable expressivity. All affected individuals had some clinical or radiologic abnormality of the feet. The phenotypic expression was so variable that the entire spectrum of dominantly inherited craniofacial dysotoses-acrocephalosyndactylys (except the typical Apert syndrome) was seen within this kindred.
Asunto(s)
Craneosinostosis/genética , Cara/anomalías , Deformidades Congénitas del Pie , Preescolar , Etnicidad , Femenino , Genes Dominantes , Humanos , Inteligencia , Masculino , Linaje , Fenotipo , ReligiónRESUMEN
Linkage analysis of Kell:PTC loci demonstration close linkage, theta = 0.045 with a lod score of 10.78. The results, which include the Sutter blood group, support the hypothesis that Sutter is a part of the Kell system.