RESUMO
Androgenetic alopecia (AGA, male pattern baldness) is the most common form of hair loss. The origin of AGA is genetic, with the X chromosome located androgen receptor gene (AR) being the only risk gene identified to date. We present the results of a genome-wide linkage study of 95 families and linkage fine mapping of the 3q21-q29, 11q14-q25, 18p11-q23, and 19p13-q13 regions in an extended sample of 125 families of German descent. The locus with strongest evidence for linkage was mapped to 3q26 with a nonparametric linkage (NPL) score of 3.97 (empirical p value = 0.00055). This is the first step toward the identification of new susceptibility genes in AGA, a process which will provide important insights into the molecular and cellular basis of scalp hair loss.
Assuntos
Alopecia/genética , Cromossomos Humanos Par 3/genética , Ligação Genética , Predisposição Genética para Doença , Adulto , Idade de Início , Mapeamento Cromossômico , Família , Testes Genéticos , Genoma Humano/genética , Humanos , MasculinoRESUMO
We report a 3-year-old girl with autosomal dominant inherited Waardenburg syndrome type I showing circumscribed hypopigmentation of the skin, heterochromia iridis, sensorineural deafness, and dental aberrations. Clinical diagnosis was confirmed by the identification of an underlying missense mutation (C811T) in the PAX3 gene. Early diagnosis of Waardenburg syndrome among children with pigment anomalies enables a successful interdisciplinary medical care.
Assuntos
Hipopigmentação/patologia , Doenças da Íris/patologia , Síndrome de Waardenburg/patologia , Anodontia/genética , Anodontia/patologia , Pré-Escolar , Feminino , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/patologia , Humanos , Hipopigmentação/genética , Doenças da Íris/genética , Mutação de Sentido Incorreto , Fator de Transcrição PAX3 , Fatores de Transcrição Box Pareados/genética , Síndrome de Waardenburg/genéticaRESUMO
Alopecia areata (AA) is a common hair loss disorder, which is thought to be a tissue-specific autoimmune disease. Previous research has identified a few AA susceptibility genes, most of which are implicated in autoimmunity. To identify new genetic variants and further elucidate the genetic basis of AA, we performed a genome-wide association study using the strategy of pooled DNA genotyping (729 cases, 656 controls). The strongest association was for variants in the HLA region, which confirms the validity of the pooling strategy. The selected top 61 single-nucleotide polymorphisms (SNPs) were analyzed in an independent replication sample (454 cases, 1364 controls). Only one SNP outside of the HLA region (rs304650) showed significant association. This SNP was then analyzed in a second independent replication sample (537 cases, 657 controls). The finding was not replicated on a significant level, but showed the same tendency. A combined analysis of the two replication samples was then performed, and the SNP rs304650 showed significant association with P=3.43 × 10(-4) (OR=1.24 (1.10-1.39)). This SNP maps to an intronic region of the SPATA5 (spermatogenesis-associated protein 5) gene on chromosome 4. The results therefore suggest the SPATA5 locus is a new susceptibility locus for AA.
Assuntos
Alopecia em Áreas/genética , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Alelos , Estudos de Casos e Controles , Seguimentos , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos TestesRESUMO
We carried out a genome-wide association study in 296 individuals with male-pattern baldness (androgenetic alopecia) and 347 controls. We then investigated the 30 best SNPs in an independent replication sample and found highly significant association for five SNPs on chromosome 20p11 (rs2180439 combined P = 2.7 x 10(-15)). No interaction was detected with the X-chromosomal androgen receptor locus, suggesting that the 20p11 locus has a role in a yet-to-be-identified androgen-independent pathway.
Assuntos
Alopecia/genética , Cromossomos Humanos Par 20/genética , Predisposição Genética para Doença , Adulto , Feminino , Genoma Humano/genética , Alemanha , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Alopecia areata (AA) is a common dermatological disease, which affects nearly 2% of the general population. Association of AA with atopic disease has been repeatedly reported. Loss-of-function mutations in the filaggrin gene (FLG) may be considered as promising candidates in AA, as they have been observed to be a strong risk factor in atopic dermatitis. The FLG mutations R501X and 2282del4 were genotyped in a large sample of AA patients (n=449) and controls (n=473). Although no significant association was observed in the patient sample overall, FLG mutations were significantly associated with the presence of atopic dermatitis among AA patients. Furthermore, the presence of FLG mutations had a strong impact on the clinical course of AA in comorbid patients. For example, 19 of the 22 mutation carriers among AA patients with atopic dermatitis showed a severe form of the disease (P=0.003; odds ratio (OR)=5.47 (95% confidence interval (CI): 1.59-18.76)). In conclusion, our data suggest that when AA occurs in conjunction with FLG-associated atopic disorder, the clinical presentation of AA may be more severe.