RESUMO
A pair of 2-year-old female monozygotic twins presented with short and brittle hair. There was marked reduction in hair density, and excessive curving of the eyelashes. Onychodystrophy was also evident. They also had developmental delay in verbal and motor skills. Neither their parents nor other relatives were known to be affected, and there was no history of consanguinity. Examination of the hair shaft under light microscopy showed trichoschisis, which was more evident under electron microscopy. Under polarized light, the hair shafts showed the pathognomonic 'tiger-tail' pattern. The level of sulphur in the hair was low. Both patients were negative for TTDN1 mutation. Clinical correlation was performed and the diagnosis of Sabinas syndrome was made. Sabinas syndrome is a very rare autosomal recessive disorder first described in a group of patients from a small community in north-eastern Mexico. It is diagnosable at birth, and its major symptoms include brittle hair, mental retardation and nail dysplasia. Structural hair abnormalities are seen by both light and electron microscopy.
Assuntos
Doenças em Gêmeos/diagnóstico , Síndromes de Tricotiodistrofia/diagnóstico , Pré-Escolar , Doenças em Gêmeos/patologia , Feminino , Cabelo/ultraestrutura , Humanos , Síndromes de Tricotiodistrofia/classificação , Síndromes de Tricotiodistrofia/patologia , Gêmeos MonozigóticosRESUMO
We report a large Mexican kindred with a variant form of congenital universal hypertrichosis that is inherited in an apparent X-linked recessive manner. In addition to the generalized hypertrichosis, the affected individuals have dental malformations and deafness. Males are more severely affected than females who exhibit only mild hypertrichosis, but not deafness or dental anomalies. Haplotype analysis in this pedigree revealed linkage to a 13-cM region on chromosome Xq24-q27.1 between markers GATA198A10 and DXS8106. Localization of the gene underlying this form of hypertrichosis is the initial step in identifying genes on the X chromosome that are involved in the control of hair growth and development.
Assuntos
Cromossomos Humanos X , Surdez/genética , Ligação Genética , Hipertricose/congênito , Hipertricose/genética , Anormalidades Dentárias/genética , Mapeamento Cromossômico , Análise Mutacional de DNA , Feminino , Genes Recessivos , Genótipo , Haplótipos , Humanos , Masculino , México , Linhagem , FenótipoRESUMO
Monilethrix is an autosomal dominant hair disorder characterized by a beaded appearance of the hair resulting from periodic thinning of the shaft (MIM 158000). The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. Mutations of the helix-encoded region in two hair-specific keratins (hHb1 and hHb6) have been identified as responsible for this disorder. We investigated two unrelated families from Russia and Colombia with monilethrix and found two missense mutations in hHb6. In the Russian family, we found a G to A transition at the first base of codon 402, resulting in a lysine substitution (GAG to AAG), designated E402K. In the Colombian family, affected patients carried a missense mutation of codon 413, involving a transition from G to A causing a lysine substitution (GAG to AAG), designated E413K. These two mutations have been identified in other monilethrix families from Europe. Our findings extend the body of evidence implicating recurrent hHb6 and hHb1 mutations in monilethrix families from around the world.
Assuntos
Doenças do Cabelo/genética , Queratinas/genética , Mutação de Sentido Incorreto/genética , Colômbia/etnologia , Análise Mutacional de DNA , Feminino , Ácido Glutâmico/metabolismo , Humanos , Lisina/biossíntese , Masculino , Linhagem , Federação Russa/etnologiaRESUMO
Variegate porphyria (VP; OMIM 176200) is characterized by a partial defect in the activity of protoporphyrinogen oxidase (PPO), the seventh enzyme of the porphyrin-heme biosynthetic pathway. The disease is usually inherited as an autosomal dominant trait displaying incomplete penetrance. In an effort to characterize the spectrum of molecular defects in VP, we identified 3 distinct mutations in 6 VP families from Chile by PCR, heteroduplex analysis, automated sequencing, restriction enzyme digestion and haplotyping analysis. The mutations consisted of 2 deletions and 1 missense mutation, designated 1239delTACAC, 1330delT and R168H. The occurrence of the missense mutation R168H had been reported previously in American, German and Dutch VP families, suggesting that this may represent a frequent recurrent mutation. Interestingly, the mutation 1239delTACAC was found in patients from 4 unrelated families living in different parts of Chile, suggesting that it might represent a common mutation in Chile. Haplotype analysis using 15 microsatellite markers which closely flank the PPO gene on chromosome 1q22, spanning approximately 21 cM, revealed the presence of R168H on different haplotypes in 6 VP patients from 3 unrelated families. In contrast, we found the occurrence of 1239delTACAC on the same chromosome 1 haplotype in 11 mutation carriers from 4 unrelated families with VP. These findings are consistent with R168H representing a hotspot mutation and 1239delTACAC existing as a founder mutation in the PPO gene. Our data comprise the first genetic studies of the porphyrias in South America and will streamline the elucidation of the genetic defects in VP patients from Chile by allowing an initial screening for the founder mutation 1239delTACAC.
Assuntos
Efeito Fundador , Mutação , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Oxirredutases/genética , Porfirias Hepáticas/genética , Chile , Feminino , Flavoproteínas , Humanos , Masculino , Proteínas Mitocondriais , Mutação de Sentido Incorreto , Porfirias Hepáticas/enzimologia , Protoporfirinogênio Oxidase , Deleção de SequênciaRESUMO
BACKGROUND: Recent success in identifying candidate genes and demonstrating mutations in such genes has set the stage for DNA-based prenatal diagnosis of genodermatoses. An example of such conditions is epidermolysis bullosa in which discrete mutations have been identified in different forms of the disease. The severity of the clinical phenotype in some forms of epidermolysis bullosa appears to justify prenatal diagnosis in families at risk for recurrence of the disease. OBSERVATIONS: DNA-based prenatal diagnosis can be performed on chorionic villi, which can be obtained as early as the eighth week of gestation. Thus, the approaches that use sensitive and specific molecular probes will allow identification of a fetus at risk relatively early during the pregnancy. Such prenatal diagnosis has successfully been performed in families with recessive dystrophic epidermolysis bullosa using type VII collagen-specific markers. CONCLUSIONS: Combination of informative intragenic and flanking DNA markers, and eventual identification of specific mutations in additional families with recessive dystrophic epidermolysis bullosa, is expected to allow early prenatal diagnosis in most families at risk for this devastating skin disease. An emerging technology in the field of prenatal genetics involves blastomere analysis prior to implantation. These DNA-based technologies will undoubtedly replace invasive skin biopsy in cases where candidate genes or specific mutations have been identified. Finally, identification of specific mutations will provide the foundation for potential gene replacement therapy in individuals affected with severe skin diseases.