RESUMO
A 22-week fetus who had died in utero had a markedly hypoplastic nose and other facial abnormalities, short fingers, hypoplastic nails, and small phallus. Radiologically there was symmetrical cartilaginous stippling of the vertebral column, femoral heads, calcanei and elbows typical of chondrodysplasia punctata (CP), and metacarpal shortness and tiny pyramidal phalanges. The several causally different forms of CP are tabulated. Differential diagnosis suggests that the present case, which does not have limb shortness, could be a case of X-linked recessive brachytelephalangic chondrodysplasia punctata.
Assuntos
Anormalidades Múltiplas/genética , Condrodisplasia Punctata/genética , Morte Fetal/genética , Cromossomo X , Condrodisplasia Punctata/etiologia , Face/anormalidades , Dedos/anormalidades , Genes Recessivos , Humanos , Recém-Nascido , Masculino , Pênis/anormalidadesRESUMO
A male fetus with multiple congenital abnormalities is reported. The parents of the fetus are consanguineous. There were unusual facial features, digital anomalies, cleft palate, a malformed tongue that prevented swallowing, absent clavicles and genital hypoplasia. The fetus had features suggestive of both Crane-Heise syndrome and aminopterin syndrome sine aminopterin (ASSAS), and may represent part of a spectrum of abnormalities including these conditions.
Assuntos
Anormalidades Múltiplas/embriologia , Face/anormalidades , Ossos Faciais/anormalidades , Anormalidades Múltiplas/diagnóstico por imagem , Adulto , Aminopterina , Consanguinidade , Feminino , Morte Fetal , Humanos , Masculino , Gravidez , RadiografiaAssuntos
Cromossomos Humanos Par 22/genética , Cardiopatias Congênitas/genética , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Deleção Cromossômica , Consanguinidade , Anormalidades Craniofaciais/patologia , Síndrome de DiGeorge/genética , Saúde da Família , Evolução Fatal , Heterozigoto , Homozigoto , Humanos , Lactente , Recém-Nascido , Repetições de Microssatélites , Linhagem , Fenótipo , SíndromeAssuntos
Cromossomos Humanos Par 13 , Trissomia , Anormalidades Múltiplas , Humanos , Masculino , SíndromeRESUMO
Prenatal diagnosis of an IVF pregnancy in a woman aged 41 years showed a fetus mosaic for trisomy 15. The fetus had dysmorphic features, hypoplastic adrenal glands, and an accessory spleen. Both IVF and advanced maternal age would seem to increase the risk of trisomy 15.
Assuntos
Cromossomos Humanos Par 15 , Feto/anormalidades , Mosaicismo/genética , Trissomia , Aborto Eugênico , Fertilização in vitro , Humanos , Masculino , Diagnóstico Pré-NatalRESUMO
A fetus is described with anophthalmia, absent pituitary, hypoplastic adrenal glands and kidneys, absent left horn of the uterus, underdeveloped genitalia, and clinodactyly, with a deletion of 14(q22q23). A review of published reports found no similar deletion cases.
Assuntos
Anoftalmia/genética , Aberrações Cromossômicas , Deleção Cromossômica , Transtornos Cromossômicos , Cromossomos Humanos Par 14/ultraestrutura , Hipófise/anormalidades , Células Cultivadas , Feminino , Humanos , Recém-NascidoRESUMO
Supravalvular aortic stenosis (SVAS) may occur as an isolated autosomal dominant trait or as a feature of Williams syndrome. It has been suggested that a defect in calcitonin function may play a role in Williams syndrome. We have excluded calcitonin as a candidate gene for SVAS using a gene specific probe.
Assuntos
Estenose da Valva Aórtica/genética , Calcitonina/genética , Marcadores Genéticos , Feminino , Genes Dominantes , Humanos , Hipercalcemia/genética , Masculino , Linhagem , SíndromeRESUMO
We describe a sibship of three males, including monozygous twins, with cerebral and cerebellar malformations and congenital lymphedema. The parents of these children are related, being half second cousins. The clinical, radiologic and histopathologic features do not fit a previously recognized pattern. We feel this sibship represents a syndrome that has not been previously described, though it closely resembles the Walker Warburg syndrome.
Assuntos
Cerebelo/anormalidades , Linfedema/diagnóstico , Encéfalo/diagnóstico por imagem , Inibição de Migração Celular , Cerebelo/diagnóstico por imagem , Córtex Cerebral/anormalidades , Córtex Cerebral/diagnóstico por imagem , Pré-Escolar , Consanguinidade , Deficiências do Desenvolvimento/etiologia , Eletroencefalografia , Potenciais Evocados Visuais , Humanos , Linfedema/congênito , Imageamento por Ressonância Magnética , Masculino , Linhagem , RadiografiaRESUMO
We report a case of a female infant with a de novo deletion of the short arm of chromosome 9, sex reversal, and an apparently intact SRY gene. Sex reversal has been reported in a number of subjects with a normal Y chromosome and a deletion of the terminal segment of the short arm of chromosome 9. The factors controlling early development of the male testes are unknown. There are likely to be many genes involved and we present additional evidence that one of these is situated on the end of the short arm of chromosome 9.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 9 , Disgenesia Gonadal 46 XY/genética , Sequência de Bases , Bandeamento Cromossômico , Transtornos do Desenvolvimento Sexual , Feminino , Humanos , Lactente , Deficiência Intelectual/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
Acute intermittent porphyria (AIP) is a low-penetrant, autosomal dominant disorder caused by mutations in the HMBS gene. The gene is transcribed from two promoters to produce ubiquitous and erythroid isoforms of porphobilinogen deaminase, which differ only at their NH2 ends. In the classical form of AIP, both isoforms are deficient, but about 5% of families have the non-erythroid variant in which only the ubiquitous isoform is affected. Previously identified mutations in this variant have been within or close to the coding region of exon 1 of the HMBS gene, the only exon that is expressed solely in the ubiquitous isoform. Here, we describe mutations in the ubiquitous promoter (-154delG) and in exon 3 (41delA) that cause the non-erythroid variant. Reporter gene and electrophoretic mobility shift assays show that the G nucleotide at position -154, the most 5' of several transcription-initiation sites in the ubiquitous HMBS promoter, which lies immediately 3' to a transcription-factor IIB binding motif, is essential for normal transcription. The frameshift mutation in exon 3 introduces a stop codon into mRNA for the ubiquitous isoform only. Our investigations identify two new mechanisms for production of the non-erythroid variant of AIP and demonstrate that mutational analysis for diagnosis of this variant needs to include wider regions of the HMBS gene than indicated by previous reports. Furthermore, they show that deletion of one of several transcription initiation sites in the promoter of a housekeeping gene that lacks both TATA and initiator elements can produce disease.
Assuntos
Éxons , Mutação da Fase de Leitura , Hidroximetilbilano Sintase/genética , Porfiria Aguda Intermitente/genética , Regiões Promotoras Genéticas , Adolescente , Adulto , Sequência de Bases , Sítios de Ligação , Pré-Escolar , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Porfiria Eritropoética/genética , Isoformas de Proteínas/genética , Fator de Transcrição TFIIB , Fatores de Transcrição/metabolismoRESUMO
We report a family with pachydermoperiostosis (idiopathic hypertrophic osteoarthropathy) spanning four generations with 10 affected individuals, four of whom are children although pachydermoperiostosis is rare in childhood. In this family, with intermarriage, the inheritance is autosomal recessive and it is possible that there are individuals who are homozygous for the pachydermoperiostosis gene. These individuals do not appear to be more severely affected, although one of them had a cleft palate and congenital heart defect which may be a manifestation of being homozygous.
Assuntos
Osteoartropatia Hipertrófica Primária/complicações , Asma/complicações , Criança , Pré-Escolar , Fissura Palatina/complicações , Consanguinidade , Permeabilidade do Canal Arterial/complicações , Feminino , Humanos , Masculino , Osteoartropatia Hipertrófica Primária/diagnóstico por imagem , Osteoartropatia Hipertrófica Primária/genética , Linhagem , RadiografiaRESUMO
Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by white patches of skin and hair. Melanocytes are lacking in these hypopigmented regions, the result of mutations of the KIT gene, which encodes the cell surface receptor for steel factor (SLF). We describe the analysis of 26 unrelated patients with piebaldism-like hypopigmentation--17 typical patients, 5 with atypical clinical features or family histories, and 4 with other disorders that involve white spotting. We identified novel pathologic mutations or deletions of the KIT gene in 10 (59%) of the typical patients, and in 2 (40%) of the atypical patients. Overall, we have identified pathologic KIT gene mutations in 21 (75%) of 28 unrelated patients with typical piebaldism we have studied. Of the patients without apparent KIT mutations, none have apparent abnormalities of the gene encoding SLF itself (MGF), and genetic linkage analyses in two of these families are suggestive of linkage of the piebald phenotype to KIT. Thus, most patients with typical piebaldism appear to have abnormalities of the KIT gene.
Assuntos
Mutação , Piebaldismo/genética , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Receptores de Fator Estimulador de Colônias/genética , Adolescente , Adulto , Sequência de Aminoácidos , Sequência de Bases , Southern Blotting , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Genes , Genes Dominantes , Fatores de Crescimento de Células Hematopoéticas/deficiência , Fatores de Crescimento de Células Hematopoéticas/genética , Humanos , Escore Lod , Masculino , Dados de Sequência Molecular , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas c-kit , Receptores Proteína Tirosina Quinases/deficiência , Receptores de Fator Estimulador de Colônias/deficiência , Deleção de Sequência , Fator de Células-TroncoRESUMO
Dominant optic atrophy (DOA) is the commonest form of inherited optic neuropathy. Although heterogeneous, a major locus has been mapped to chromosome 3q28 and the gene responsible, OPA1, was recently identified. We therefore screened a panel of 35 DOA patients for mutations in OPA1. This revealed 14 novel mutations and a further three known mutations, which together accounted for 20 of the 35 families (57%) included in this study. This more than doubles the number of OPA1 mutations reported in the literature, bringing the total to 25. These are predominantly null mutations generating truncated proteins, strongly suggesting that the mechanism underlying DOA is haploinsufficiency. The mutations are largely family-specific, although a common 4 bp deletion in exon 27 (eight different families) and missense mutations in exons 8 (two families) and 9 (two families) have been identified. Haplotype analysis of individuals with the exon 27 2708del(TTAG) mutation suggests that this is a mutation hotspot and not an ancient mutation, thus excluding a major founder effect at the OPA1 locus. The mutation screening in this study also identified a number of asymptomatic individuals with OPA1 mutations. A re-calculation of the penetrance of this disorder within two of our families indicates figures as low as 43 and 62% associated with the 2708del(TTAG) mutation. If haploinsufficiency is the mechanism underlying DOA it is unlikely that this figure will be mutation-specific, indicating that the penetrance in DOA is much lower than the 98% reported previously. To investigate whether Leber's hereditary optic neuropathy (LHON) could be caused by mutations in OPA1 we also screened a panel of 28 LHON patients who tested negatively for the three major LHON mutations. No mutations were identified in any LHON patients, indicating that DOA and LHON are genetically distinct.