RESUMO
Zimmermann-Laband syndrome (ZLS) is an autosomal dominant disorder characterized by gingival fibromatosis, absent or dysplastic distal phalanges, vertebral defects, hepatosplenomegaly, hypertrichosis and sometimes mental retardation. We describe two unrelated patients, a girl aged 9 years and a boy 11 months whose clinical and radiological findings permit us to diagnose the ZLS. Body overgrowth, present in both patients, was identified as a main clinical feature not previously reported as well as the presence in neuroimaging studies of a cavernous hemangioma on the frontal and the left cerebellar regions in the boy. The girl also presented important radiological characteristics such as broad medulary canals and metaphyses of long bones, thin cortices, broad ribs, accelerated skeletal maturation as well as high intelligence level. A wide clinical spectrum in ZLS is also considered.
Assuntos
Transtornos Cromossômicos/genética , Fibromatose Gengival/complicações , Fibromatose Gengival/genética , Hipertricose/complicações , Hipertricose/genética , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Convulsões/complicações , Convulsões/genética , Criança , Feminino , Humanos , SíndromeRESUMO
BACKGROUND: Hypomelanosis of Ito (HI) is a neurocutaneous phenotype that reflects different mosaicisms, including functional imbalances secondary to chromosome-X inactivation patterns in certain X;autosome translocation carriers. METHODS: We assessed X inactivation patterns by means of the human androgen receptor (HUMARA) assay and BrdU labeling in affected and unaffected skin of a young female with HI and a de novo t(X;13)(Xp13q;Xq13p). PCR analysis was carried out in DNA extracted from uncultured and cultured skin, whereas the BrdU replication patterns were sought in cultured fibroblasts. Parental DNA was also tested. Fluorescence in situ hybridization (FISH) with X and 13/21 centromere probes (DXZ2 and D13Z1/D21Z1) and a cosmid for the X inactivation center were also performed to refine breakpoint assignments. RESULTS: An X inactivation pattern implying functional Xpter-->q11 disomy was found in DNA extracted from uncultured hypopigmented skin, whereas preferential inactivation of the normal X was observed in uncultured normal skin as well as in cultured fibroblasts (after one passage) from both affected and unaffected skin areas. PCR analysis also showed paternal origin of the translocation. BrdU labeling of metaphases from hypopigmented and normal skin primary cultures showed der(Xq13p) to be inactive in about 25% of the cells. FISH revealed that der(Xp13q) had a compound centromere, whereas der(Xq13p) retained 13 centromere repeats but lacked X centromere sequences. Hence, breakpoints were assigned to Xq11 and 13q10. The X inactivation center cosmid gave a signal on both normal X and der(Xp13q), indicating that the inactivation center was not disrupted by the translocation. CONCLUSIONS: These findings confirm that mosaic functional Xp disomy, rather than disruption of X-linked genes, is associated with HI and involvement of the central nervous system (CNS) in some carriers of a structurally balanced X;autosome translocation.
Assuntos
Piebaldismo/genética , Cromossomo X , Cromossomos Humanos Par 13 , Mecanismo Genético de Compensação de Dose , Feminino , Humanos , Cariotipagem , Reação em Cadeia da Polimerase , Translocação GenéticaRESUMO
A mother and a daughter affected with multiple trichoepithelioma were studied. The age of onset of the symptomatology in both was 7-years-old, the daughter being more severely affected than the mother at this age. This early age of onset is an exceptional observation which could be explained by maternal imprinting.
Assuntos
Aberrações Cromossômicas/genética , Neoplasias Faciais/genética , Genes Dominantes/genética , Neoplasia de Células Basais/genética , Neoplasias Primárias Múltiplas/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Cutâneas/genética , Adulto , Criança , Transtornos Cromossômicos , Feminino , Expressão Gênica/fisiologia , Humanos , FenótipoAssuntos
Códon sem Sentido/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , RNA Mensageiro/metabolismo , Síndrome de Smith-Lemli-Opitz/genética , Adulto , Alelos , Células Cultivadas , Colesterol/metabolismo , Códon sem Sentido/genética , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Recém-Nascido , Masculino , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Fenótipo , Gravidez , Síndrome de Smith-Lemli-Opitz/sangue , Síndrome de Smith-Lemli-Opitz/diagnóstico , Síndrome de Smith-Lemli-Opitz/metabolismoRESUMO
We report on a 16 month old girl with hypomelanosis of Ito and a balanced de novo (X;13)(q10;q10) translocation in which the der(Xp13q) had the X centromere (as assessed by FISH with the DXZ3 probe). A functional Xp disomy was shown in a small proportion of cultured lymphocytes by means of a BrdU terminal pulse. This observation supports the notion of a distinct form of hypomelanosis of Ito resulting from a functional Xp disomy.
Assuntos
Cromossomos Humanos Par 13 , Transtornos da Pigmentação/genética , Translocação Genética , Cromossomo X , Adulto , Criança , Pré-Escolar , Bandeamento Cromossômico , Mecanismo Genético de Compensação de Dose , Feminino , Humanos , Lactente , Recém-Nascido , Cariotipagem , PloidiasRESUMO
The unusual karyotype of Ellobius lutescens (2n = 17,X in males and females) has attracted permanent interest and prompted a series of hypotheses on sex determination in this species since its first description by Matthey (1953). The developing knowledge about the sex chromosomes and sex determination as well as the availability of new cytogenetic and molecular genetic techniques prompted studies to test the compatibility between current hypotheses and new findings and rendered modifications of the hypotheses necessary. After a long period dominated by the question what the sex chromosome constitution of this species might be and where the testis determining factor could be located, the presence of Sry had been eventually excluded and sex determination attributed to a hypothetical mutated gene acting downstream of Sry. An X-chromosomal or autosomal location of this gene can be assessed by cosegregation of sex with X-chromosome markers. Some preliminary results concerning X-chromosome dinucleotide repeat markers are reported. However, these markers were homomorphic in Ellobius lutescens. We now report evidence that Zfy is also missing in Ellobius lutescens and E. tancrei (males and females XX), a finding from which we conclude that the entire Y chromosome has been lost from these species. Perspectives concerning future studies are discussed.