RESUMEN
While there have been significant advances in understanding the genetic etiology of human hair loss over the previous decade, there remain a number of hereditary disorders for which a causative gene has yet to be identified. We studied a large, consanguineous Brazilian family that presented with woolly hair at birth that progressed to severe hypotrichosis by the age of 5, in which 6 of the 14 offspring were affected. After exclusion of known candidate genes, a genome-wide scan was performed to identify the disease locus. Autozygosity mapping revealed a highly significant region of extended homozygosity (lod score of 10.41) that contained a haplotype with a linkage lod score of 3.28. Results of these two methods defined a 9-Mb region on chromosome 13q14.11-q14.2. The interval contains the P2RY5 gene, in which we recently identified pathogenic mutations in several families of Pakistani origin affected with autosomal recessive woolly and sparse hair. After the exclusion of several other candidate genes, we sequenced the P2RY5 gene and identified a homozygous mutation (C278Y) in all affected individuals in this family. Our findings show that mutations in P2RY5 display variable expressivity, underlying both hypotrichosis and woolly hair, and underscore the essential role of P2RY5 in the tissue integrity and maintenance of the hair follicle.
Asunto(s)
Genes Recesivos , Predisposición Genética a la Enfermedad , Hipotricosis/genética , Mutación , Receptores Purinérgicos P2/genética , Secuencia de Aminoácidos , Animales , Brasil , Mapeo Cromosómico , Cromosomas Humanos Par 13/genética , Femenino , Ligamiento Genético , Humanos , Escala de Lod , Masculino , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Linaje , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADNRESUMEN
This report describes a well-documented case of primary, nodular-form tuberculosis of the breast that mimicked cancer in a 73-year-old patient. This is a disease that rarely affects the breast.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Carcinoma/diagnóstico , Mastitis/diagnóstico , Tuberculosis/diagnóstico , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Mastitis/microbiología , Mycobacterium tuberculosis , Tuberculosis/microbiologíaRESUMEN
OBJECTIVE: This study aims to evaluate the effect of raloxifene on the expression of human telomerase reverse transcriptase (hTERT) in invasive ductal breast carcinoma of postmenopausal women. STUDY DESIGN: This study included 20 postmenopausal women with invasive, stage II, estrogen receptor-positive ductal carcinoma diagnosed by incisional biopsy, who received 60 mg of raloxifene orally for 28 days prior to definitive surgery. On the 29th day of treatment, definitive surgery was performed and a second tumor sample was taken for analysis. The catalytic subunit of telomerase (hTERT) was evaluated semiquantitatively by immunohistochemistry in the tumor samples obtained prior to and following raloxifene use and the results were analyzed using the McNemar test (p<0.05). RESULTS: The samples of 17 patients (85%) were classified as positive for telomerase expression prior to raloxifene treatment, while only 6 (30%) remained positive following raloxifene treatment (p<0.0026). CONCLUSION: In the present study, raloxifene significantly reduced the expression of hTERT in estrogen receptor-positive breast tumors from postmenopausal women.