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1.
Ann Oncol ; 34(10): 849-866, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37572987

RESUMO

The management of breast cancer during pregnancy (PrBC) is a relatively rare indication and an area where no or little evidence is available since randomized controlled trials cannot be conducted. In general, advances related to breast cancer (BC) treatment outside pregnancy cannot always be translated to PrBC, because both the interests of the mother and of the unborn should be considered. Evidence remains limited and/or conflicting in some specific areas where the optimal approach remains controversial. In 2022, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process on this topic to gain insights from a multidisciplinary group of experts and develop statements on controversial topics that cannot be adequately addressed in the current evidence-based ESMO Clinical Practice Guideline. The aim of this consensus-building process was to discuss controversial issues relating to the management of patients with PrBC. The virtual meeting included a multidisciplinary panel of 24 leading experts from 13 countries and was chaired by S. Loibl and F. Amant. All experts were allocated to one of four different working groups. Each working group covered a specific subject area with two chairs appointed: Planning, preparation and execution of the consensus process was conducted according to the ESMO standard operating procedures.

2.
Clin Res Cardiol ; 105(2): 117-26, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26195125

RESUMO

BACKGROUND: New oral anticoagulants are increasingly used in women of childbearing age, but apart from one case report there is no published experience with rivaroxaban exposure during pregnancy. METHODS: From October 2008 to December 2014, the German Embryotox Pharmacovigilance Centre identified 63 exposed pregnancies among 94 requests concerning rivaroxaban use during childbearing age. Follow-up included paediatric checks until 6 weeks after birth. RESULTS: All pregnancies with completed follow-up were exposed at least during the first trimester. Treatment indications included venous thromboembolism, knee surgery, and atrial fibrillation. 37 pregnancies were prospectively ascertained and resulted in six spontaneous abortions, eight elective terminations of pregnancy, and 23 live births. All women had discontinued rivaroxaban after recognition of pregnancy, mostly in the first trimester, but in one woman treatment continued until gestational week 26. There was one major malformation (conotruncal cardiac defect) among the 37 prospectively ascertained pregnancies in a woman with complex medication and a previous foetus with cardiac malformation without exposure to rivaroxaban. Only one case of bleeding concerning a retrospective report of surgery for missed abortion was observed in our case series. CONCLUSION: Our results might give reassurance to those women, who were inadvertently exposed to rivaroxaban in early pregnancy. However, our limited cohort size does not allow ruling out an increased malformation risk and does not support the use of rivaroxaban during pregnancy. In all cases of (inadvertent) rivaroxaban exposure during 1st trimester, anticoagulation regimen should be reconsidered and a detailed ultrasound assessment recommended to confirm normal foetal development.


Assuntos
Anticoagulantes/administração & dosagem , Resultado da Gravidez , Rivaroxabana/administração & dosagem , Tromboembolia/prevenção & controle , Adulto , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Feminino , Seguimentos , Alemanha , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Farmacovigilância , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Risco , Rivaroxabana/efeitos adversos , Tromboembolia/etiologia
3.
Int J Androl ; 32(3): 226-30, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18042180

RESUMO

We report on a 30-year-old man with azoospermia, primary hypogonadism and minor dysmorphic features who carried a balanced insertional chromosome translocation inv ins (2p24;4q28.3q31.22)de novo. Molecular cytogenetic analyses of the chromosome breakpoints revealed the localization of the breakpoint in 4q28.3 between BACs RP11-143E9 and RP11-285A15, an interval that harbours the PCDH10 gene. In 4q31.22, a breakpoint-spanning clone (RP11-6L6) was identified which contains the genes LSM6 and SLC10A7. On chromosome 2, BACs RP11-531P14 and RP11-360O18 flank the breakpoint in 2p24, a region void of known genes. In conclusion, the chromosome aberration of this patient suggests a gene locus for primary hypogonadism in 2p24, 4q28.3 or 4q31.2, and three possible candidate genes (LSM6, SLC10A7 and PCDH10) were identified by breakpoint analyses.


Assuntos
Cromossomos Humanos Par 2/genética , Cromossomos Humanos Par 4/genética , Hipogonadismo/genética , Adulto , Caderinas/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Protocaderinas , Proteínas de Ligação a RNA/genética , Simportadores/genética , Translocação Genética
4.
J Med Genet ; 43(5): e22, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16648375

RESUMO

Cohen syndrome (CS) is an autosomal recessive disorder with variability in the clinical manifestations, characterised by mental retardation, postnatal microcephaly, facial dysmorphism, pigmentary retinopathy, myopia, and intermittent neutropenia. Mutations in the gene COH1 have been found in an ethnically diverse series of patients. Brief clinical descriptions of 24 patients with CS are provided. The patients were from 16 families of different ethnic backgrounds and between 2.5 and 60 years of age at assessment. DNA samples from all patients were analysed for mutations in COH1 by direct sequencing. Splice site mutations were characterised using reverse transcriptase PCR analysis from total RNA samples. In this series, we detected 25 different COH1 mutations; 19 of these were novel, including 9 nonsense mutations, 8 frameshift mutations, 4 verified splice site mutations, 3 larger in frame deletions, and 1 missense mutation. We observed marked variability of developmental and growth parameters. The typical facial gestalt was seen in 23/24 patients. Early onset progressive myopia was present in all the patients older than 5 years. Widespread pigmentary retinopathy was found in 12/14 patients assessed over 5 years of age. We present evidence for extended allelic heterogeneity of CS, with the vast majority of mutations leading to premature termination codons in COH1. Our data confirm the broad clinical spectrum of CS with some patients lacking even the characteristic facial gestalt and pigmentary retinopathy at school age.


Assuntos
Anormalidades Múltiplas/diagnóstico , Deficiência Intelectual/diagnóstico , Proteínas de Membrana/genética , Miopia/diagnóstico , Retinose Pigmentar/diagnóstico , Anormalidades Múltiplas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Mutacional de DNA , Face/anormalidades , Feminino , Heterogeneidade Genética , Humanos , Deficiência Intelectual/genética , Masculino , Pessoa de Meia-Idade , Mutação , Miopia/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Retinose Pigmentar/genética , Síndrome , Proteínas de Transporte Vesicular
7.
Eur J Hum Genet ; 12(11): 979-82, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15340363

RESUMO

Friedreich's ataxia (FRDA), the most common autosomal recessively inherited ataxia, is due to a homozygous GAA triplet repeat expansion in the first intron of the FRDA gene in about 96% of patients. Approximately 4% of FRDA patients are compound heterozygotes with a GAA repeat expansion in one allele and a point mutation in the coding region of the second allele. To reinvestigate the mutation spectrum, we searched for mutations including exon deletions in six patients heterozygous for the GAA repeat expansion and found two unknown missense mutations, p.Asn146Lys and p.Leu186Arg, in trans to the expanded FRDA allele. Interestingly, we detected a heterozygous 2776 bp deletion including exon 5a in one of our patients. This deletion removes 50 of the 210 residues of the frataxin. Furthermore, since no FRDA case with two-point mutations is known, we screened eight patients with FRDA phenotype but GAA alleles within the normal range but did not reveal a mutation within the FRDA gene. In addition, DNA polymorphisms have been found in four out of 100 control individuals in this study.


Assuntos
Sequência de Bases , Éxons , Ataxia de Friedreich/genética , Mutação de Sentido Incorreto , Deleção de Sequência , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Linhagem
9.
Ophthalmologe ; 100(11): 979-83, 2003 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-14669035

RESUMO

BACKGROUND: Schnyder's crystalline corneal dystrophy (SCCD) is a rare autosomal dominant disease and can occur in association with hyperlipoproteinemia. The disease has been mapped to chromosome 1p34.1-p36. CASE REPORT: We report on a 66-year-old woman and her son with Schnyder's crystalline corneal dystrophy. The mother had type IV hyperlipoproteinemia and hypercholesterolemia while her son had hypercholesterolemia with elevated LDL-cholesterol. Analysis of microsatellite markers within the candidate interval of 1p34.1-p36 showed that the affected son and his unaffected brother had inherited different alleles only for the proximal marker D1S228 from their affected mother. CONCLUSIONS: The haplotype analysis suggests that either recombination has occurred, which would allow the candidate interval to be narrowed down, or alternatively, the SCCD in the reported family is not linked to chromosome 1, which would be a first indication of genetic heterogeneity in this disease. To reduce the risk of cardiovascular disease, hyperlipidemia should always be excluded in patients with Schnyder's crystalline corneal dystrophy.


Assuntos
Cromossomos Humanos Par 1/genética , Distrofias Hereditárias da Córnea/sangue , Distrofias Hereditárias da Córnea/genética , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Hiperlipidemia Familiar Combinada/diagnóstico , Hiperlipidemia Familiar Combinada/genética , Adulto , Idoso , Distrofias Hereditárias da Córnea/diagnóstico , Distrofias Hereditárias da Córnea/patologia , Diagnóstico Diferencial , Feminino , Ligação Genética , Humanos , Masculino , Linhagem
10.
Neuropediatrics ; 34(1): 30-5, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12690565

RESUMO

We report three boys in whom a diagnosis of Lhermitte-Duclos disease (LDD) was assumed from characteristic neuroimaging findings. LDD was confirmed by an open biopsy in patient 1, while a biopsy in patient 2 was inconclusive. Histologic confirmation in patient 3 was deliberately not attempted. However, a follow-up observation of stable clinical and neuroimaging findings over 2, 5 and 11 years, respectively, support the diagnosis of LDD. Despite extensive expansion of the lesion with brainstem involvement, clinical signs in two boys were minimal, while one patient has cognitive impairment and a complex oculomotor disturbance. So far we found no evidence for an association with Cowden disease (CD). No germline PTEN mutations were detected in these children, but the amount of available biopsy tissue in patients 1 and 2 was insufficient for a complete genetic analysis of tumor tissue. In conclusion, LDD can usually be diagnosed by MRI. In view of the favourable natural history, a conservative "wait and see" strategy is justified, particularly if radical tumor resection is not possible. LDD is often not associated with CD and germline PTEN mutations seem not to be present in isolated LDD.


Assuntos
Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/patologia , Ganglioneuroma/diagnóstico por imagem , Ganglioneuroma/patologia , Neoplasias Cerebelares/genética , Criança , Seguimentos , Ganglioneuroma/genética , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Avaliação de Resultados em Cuidados de Saúde , Fatores de Tempo , Tomografia Computadorizada por Raios X
12.
Hum Genet ; 109(2): 159-66, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11511921

RESUMO

An inherited deficiency in beta-galactosidase can result in GM1 gangliosidosis, with several phenotypes of generalized or chronic psychomotor deterioration, as well as in Morquio disease type B, a characteristic mucopolysaccharidosis free of neurological symptoms. We performed mutation analyses in 17 juvenile and adult patients from various European regions with a deficiency in beta-galactosidase and skeletal abnormalities. Fifteen of these had the Morquio B phenotype and have remained neurologically healthy until now while the two others exhibited psychomotor retardation of juvenile onset. A two-base substitution (851-852TG-->CT; W273L) was present in 14 of the 15 Morquio B cases. Even if one excludes alleles from patients with possible common descent, there was a much higher frequency (79%) among those with Morquio B phenotype for the W273L mutation than previously reported in the literature (37%). That the Morquio phenotype is also expressed in heterozygotes for W273L and alleles typically found in GM1 gangliosidosis makes it possible to predict the phenotype and reliably detect heterozygotes. A single French patient had a novel missense point mutation (Q408P) together with a known mutation (T500A) while the mentally retarded patients were both heterozygous for two mutations known in chronic GM1 gangliosidosis together with two novel missense point mutations (Y270D and H281Y) in the vicinity of W273L. Our results confirm the high impact of Trp 273 for the function of beta-galactosidase and the expression of the Morquio B phenotype. In addition, a second domain around the amino acids 400-500 may also be of significance.


Assuntos
Análise Mutacional de DNA , Mucopolissacaridose IV/genética , Mutação Puntual , beta-Galactosidase/deficiência , Adolescente , Adulto , Criança , Pré-Escolar , Primers do DNA/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Fenótipo , RNA Mensageiro/metabolismo , Mapeamento por Restrição , Reação em Cadeia da Polimerase Via Transcriptase Reversa , beta-Galactosidase/genética
13.
Neuropediatrics ; 32(2): 57-61, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11414644

RESUMO

In 1900 the famous German neurologist Hermann Oppenheim published a two-page article on "Myatonia congenita" which led to a long-lasting and confusing discussion in neurology and neuropediatrics, and which was extensively quoted throughout the 20th century. As this article is only available in German, an English translation is presented here. Further publications of Oppenheim on the same subject are mentioned and some comments are made on the impact of his seminal article. It had the merit of drawing the attention to the existence of congenital muscle diseases in children but its impact would be better understood by the influence Oppenheim had on his time, as he was one of the leading neurologists at the end of the 19th and beginning of the 20th century.


Assuntos
Doenças Neuromusculares/história , Criança , Alemanha , História do Século XIX , História do Século XX , Humanos , Traduções
14.
Am J Hum Genet ; 68(1): 81-91, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11112658

RESUMO

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.


Assuntos
Cromossomos Humanos Par 8/genética , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/patologia , Mutação/genética , Osteocondrodisplasias/classificação , Osteocondrodisplasias/genética , Adolescente , Adulto , Sequência de Aminoácidos , Antropometria , Sequência de Bases , Estatura , Criança , Pré-Escolar , Análise Mutacional de DNA , Proteínas de Ligação a DNA/metabolismo , Fatores de Ligação de DNA Eritroide Específicos , Éxons/genética , Feminino , Genótipo , Humanos , Lactente , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/patologia , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Radiografia , Síndrome , Fatores de Transcrição/metabolismo , Dedos de Zinco/genética
15.
Eur J Hum Genet ; 8(10): 771-6, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11039577

RESUMO

Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a genetically heterogeneous neurodegenerative disorder characterised by progressive spasticity of the lower limbs. The SPG4 locus at 2p21-p22 accounts for 40-50% of all AD-HSP families. The SPG4 gene was recently identified. It is ubiquitously expressed in adult and foetal tissues and encodes spastin, an ATPase of the AAA family. We have now identified four novel SPG4 mutations in German AD-HSP families, including one large family for which anticipation had been proposed. Mutations include one frame-shift and one missense mutation, both affecting the Walker motif B. Two further mutations affect two donor splice sites in introns 12 and 16, respectively. RT-PCR analysis of both donor splice site mutations revealed exon skipping and reduced stability of aberrantly spliced SPG4 mRNA. All mutations are predicted to cause loss of functional protein. In conclusion, we confirm in German families that SPG4 mutations cause AD-HSP. Our data suggest that SPG4 mutations exert their dominant effect not by gain of function but by haploinsufficiency. If a threshold level of spastin were critical for axonal preservation, such threshold dosage effects might explain the variable expressivity and incomplete penetrance of SPG4-linked AD-HSP.


Assuntos
Adenosina Trifosfatases/genética , Códon sem Sentido/genética , Éxons/genética , Mutação da Fase de Leitura/genética , Mutação de Sentido Incorreto , Paraplegia Espástica Hereditária/genética , Repetições de Trinucleotídeos/genética , Adenosina Trifosfatases/metabolismo , Primers do DNA/química , Feminino , Genes Dominantes , Genótipo , Humanos , Masculino , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo Genético , Splicing de RNA/genética , Mapeamento por Restrição , Análise de Sequência de DNA , Espastina
16.
J Clin Endocrinol Metab ; 85(4): 1703-10, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10770218

RESUMO

X-Linked nephrogenic diabetes insipidus (NDI) is a rare inherited disorder characterized by the excretion of abnormal large volumes of diluted urine mainly caused by mutations in the V2 vasopressin receptor (AVPR2) gene. By screening NDI patients for mutations within the AVPR2 gene we have identified three novel (I46K, F105V, I130F) and four recurrent (D85N, R106C, R113W, Q225X) mutations. In addition, a recurrent missense mutation (A147T) within the aquaporin-2 gene was identified in a female patient with autosomal recessive NDI associated with sensorineural deafness. Selected clinical data of the NDI patients were compared with the results from the in vitro studies. Functional analysis of I46K and I130F revealed reduced maximum agonist-induced cAMP responses as a result of an improper cell surface targeting. In contrast, the F105V mutation is delivered to the cell surface and displayed an unchanged maximum cAMP response, but impaired ligand binding abilities of F105V were reflected in a shifted concentration-response curve toward higher vasopressin concentrations. As the extracellularly located F105 is highly conserved among the vasopressin/oxytocin receptor family, functional analysis of this residue implicates an important role in high affinity agonist binding.


Assuntos
Aquaporinas/genética , Diabetes Insípido Nefrogênico/genética , Mutação , Receptores de Vasopressinas/genética , Cromossomo X , Sequência de Aminoácidos , Animais , Aquaporina 2 , Aquaporina 6 , Arginina Vasopressina/metabolismo , Células COS , Criança , Pré-Escolar , Análise Mutacional de DNA , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Feminino , Ligação Genética , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Mutação de Sentido Incorreto , Linhagem , Reação em Cadeia da Polimerase , Receptores de Vasopressinas/química , Alinhamento de Sequência , Transfecção
17.
Neuromuscul Disord ; 9(3): 166-70, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10382910

RESUMO

X-linked Emery-Dreifuss muscular dystrophy (EDMD) is a relatively rare benign neuromuscular disorder which can vary remarkably in onset, course and severity. In the present study, a TCTAC deletion spanning the nucleotides 631-635 of the emerin gene caused an unusually severe disease phenotype including loss of ambulation and severe muscle wasting in two affected brothers. The same mutation has been reported previously in an unrelated family showing a significantly milder phenotype. The interfamilial heterogeneity in distribution and in severity of the features in the two families point to environmental or genetic modification as the cause of clinical variability in Emery-Dreifuss muscular dystrophy.


Assuntos
Proteínas de Membrana/genética , Distrofias Musculares/genética , Timopoietinas/genética , Cromossomo X/genética , Adolescente , Adulto , Sequência de Bases , Criança , Pré-Escolar , DNA/química , DNA/genética , Análise Mutacional de DNA , Saúde da Família , Feminino , Expressão Gênica , Ligação Genética , Humanos , Lactente , Masculino , Distrofias Musculares/patologia , Distrofia Muscular de Emery-Dreifuss , Proteínas Nucleares , Linhagem , Fenótipo , Deleção de Sequência
18.
Eur J Hum Genet ; 6(5): 439-44, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9801868

RESUMO

We describe the first inverted duplication of the p21.3p26 region of chromosome 3 in a child with phenotypic features of the trisomy 3p syndrome. This uncommon type of aberration was verified by multicolour fluorescence in situ hybridisation (FISH) using yeast artificial chromosome (YAC) clones from chromosome 3 (CEPH library). With a newly constructed YAC clone from the 3p26 region an unexpected subtelomeric deletion was diagnosed in the aberrant chromosome 3. Using the primed in situ labelling (PRINS) method, telomeres were found to be present on the recombinant chromosome 3. The repeated appearance of concomitant distal deletions in inverted duplications suggests that an overall mechanism exists for the origin of such duplications/deficiencies.


Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos , Cromossomos Humanos Par 3 , Cromossomos Artificiais de Levedura , Clonagem Molecular , Humanos , Hibridização in Situ Fluorescente , Telômero
19.
Hum Mol Genet ; 7(5): 855-64, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9536090

RESUMO

Seventeen families with Emery-Dreifuss muscular dystrophy (EDMD) have been studied both by DNA sequencing and by emerin protein expression. Fourteen had mutations in the X-linked emerin gene, while three showed evidence of autosomal inheritance. Twelve of the 14 emerin mutations caused early termination of translation. An in-frame deletion of six amino acids from the C-terminal transmembrane helix caused almost complete absence of emerin from muscle with no localization to the nuclear membrane, although mRNA levels were normal. This shows that mutant emerin proteins are unstable if they are unable to integrate into a membrane. A 22 bp deletion in the promoter region was expected to result in reduced emerin production, but normal amounts of emerin of normal size were found in leucocytes and lymphoblastoid cell lines. This shows that DNA analysis is necessary to exclude emerin mutations in suspected X-linked EDMD. Emerin levels in female carriers often deviated from the expected 50% and this was due, in at least two families, to skewed emerin mRNA expression from the normal and mutated alleles. In one family with a novel deletion of the last three exons of the emerin gene, a carrier had a cardiomyopathy and very low emerin levels (<5% of normal) due to skewed X-inactivation. In the three autosomal cases of EDMD, emerin was normal on western blots of blood cells, which suggests that autosomal EDMD is not caused by indirect reduction of emerin levels.


Assuntos
Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Distrofias Musculares/genética , Mutação/genética , Timopoietinas/biossíntese , Timopoietinas/genética , Adolescente , Adulto , Linhagem Celular Transformada , Criança , Análise Mutacional de DNA , Feminino , Humanos , Linfócitos , Masculino , Pessoa de Meia-Idade , Distrofias Musculares/metabolismo , Distrofia Muscular de Emery-Dreifuss , Proteínas Nucleares , Linhagem , Cromossomo X/genética
20.
Ann Hum Genet ; 62(Pt 5): 397-400, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10088036

RESUMO

HNA is an autosomal dominant recurrent focal neuropathy involving the brachial plexus. The etiology of HNA is unknown but the genetic defect most likely affects a non-neuronal tissue. We previously described linkage to chromosome 17q24-q25 in two HNA-families. Here we report the mutation analysis of two candidate genes: a cDNA encoding a putative sialyltransferase and the SFRS2 splicing factor including the c-myb ET-locus which is encoded on the opposite strand of the SFRS2 gene. The complete protein coding regions of both genes were studied by direct DNA sequencing. We did not find a disease associated mutation indicating that these genes are most likely not involved in the pathogenesis of HNA. However, we identified and characterized a rare AvaII polymorphism in the SFRS2 gene and detected a sequencing error, leading to an amino acid change (Val11Leu) in the published sequence of the putative sialyltransferase.


Assuntos
Neurite do Plexo Braquial/genética , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas/genética , Ribonucleoproteínas , Sialiltransferases/genética , Transativadores/genética , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Modelos Genéticos , Linhagem , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Proteínas Proto-Oncogênicas c-myb , Fatores de Processamento de Serina-Arginina
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