Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
Ugeskr Laeger ; 181(38)2019 Sep 16.
Artigo em Dinamarquês | MEDLINE | ID: mdl-31538580

RESUMO

This is a case report of a 36-year-old woman with un-explained recurrent pregnancy loss, and during her recent pregnancy there were signs of hydrops foetalis. Chorionic villus sampling with array-comparative genomic hybrid-isation revealed an 8.6 Mb duplication of 6q26q27 and a deletion of 14q32.31q32.33. Subsequent genetic exam-inations of the parents with fluorescence in situ hybrid-isation showed a submicroscopically balanced translocation on the patient's chromosomes 6 and 14, which explained her recurrent abortions, and which could not be detected with the conventional genetic testing G-band-karyotyping.

2.
PLoS Genet ; 14(11): e1007780, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30419018

RESUMO

Clustered copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) are often reported as germline chromothripsis. However, such cases might need further investigations by massive parallel whole genome sequencing (WGS) in order to accurately define the underlying complex rearrangement, predict the occurrence mechanisms and identify additional complexities. Here, we utilized WGS to delineate the rearrangement structure of 21 clustered CNV carriers first investigated by CMA and identified a total of 83 breakpoint junctions (BPJs). The rearrangements were further sub-classified depending on the patterns observed: I) Cases with only deletions (n = 8) often had additional structural rearrangements, such as insertions and inversions typical to chromothripsis; II) cases with only duplications (n = 7) or III) combinations of deletions and duplications (n = 6) demonstrated mostly interspersed duplications and BPJs enriched with microhomology. In two cases the rearrangement mutational signatures indicated both a breakage-fusion-bridge cycle process and haltered formation of a ring chromosome. Finally, we observed two cases with Alu- and LINE-mediated rearrangements as well as two unrelated individuals with seemingly identical clustered CNVs on 2p25.3, possibly a rare European founder rearrangement. In conclusion, through detailed characterization of the derivative chromosomes we show that multiple mechanisms are likely involved in the formation of clustered CNVs and add further evidence for chromoanagenesis mechanisms in both "simple" and highly complex chromosomal rearrangements. Finally, WGS characterization adds positional information, important for a correct clinical interpretation and deciphering mechanisms involved in the formation of these rearrangements.

3.
Stem Cell Res ; 33: 46-50, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30312873

RESUMO

Bardet-Biedl syndrome (BBS) is genetically heterogeneous with at least 21 genes involved, and BBS10 encodes, together with BBS6 and BBS12, chaperonin-like proteins which are important for the assembly of the multiprotein complex, the BBSome encoded by other BBS genes. Here we describe the successful generation of an induced pluripotent stem cell (iPSC) line KCi002-A from a male with BBS, homozygous for the disease causing variant c.271insT, p.(Cys91fsX95) in BBS10. Resource table.

4.
Eur J Hum Genet ; 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30291340

RESUMO

Deletions on chromosome 15q14 are a known chromosomal cause of cleft palate, typically co-occurring with intellectual disability, facial dysmorphism, and congenital heart defects. The identification of patients with loss-of-function variants in MEIS2, a gene within this deletion, suggests that these features are attributed to haploinsufficiency of MEIS2. To further delineate the phenotypic spectrum of the MEIS2-related syndrome, we collected 23 previously unreported patients with either a de novo sequence variant in MEIS2 (9 patients), or a 15q14 microdeletion affecting MEIS2 (14 patients). All but one de novo MEIS2 variant were identified by whole-exome sequencing. One variant was found by targeted sequencing of MEIS2 in a girl with a clinical suspicion of this syndrome. In addition to the triad of palatal defects, heart defects, and developmental delay, heterozygous loss of MEIS2 results in recurrent facial features, including thin and arched eyebrows, short alae nasi, and thin vermillion. Genotype-phenotype comparison between patients with 15q14 deletions and patients with sequence variants or intragenic deletions within MEIS2, showed a higher prevalence of moderate-to-severe intellectual disability in the former group, advocating for an independent locus for psychomotor development neighboring MEIS2.

5.
Stem Cell Res ; 31: 235-239, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30142598

RESUMO

Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy with a wide range of symptoms including obesity, retinal dystrophy, polycystic kidney disease, polydactyly, hypogonadism and learning difficulties. Here we describe the successful generation of an induced pluripotent stem cell (iPSC) KCi001-A from a BBS patient compound heterozygous for two disease causing BBS1 variants c.1169T>G, p. (Met390Arg)/c.1135G>C, p.(Gly370Arg). Resource table.

6.
Eur J Med Genet ; 2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29959045

RESUMO

INTRODUCTION: MED13L-related intellectual disability is characterized by moderate intellectual disability (ID), speech impairment, and dysmorphic facial features. We present 8 patients with MED13L-related intellectual disability and review the literature for phenotypical and genetic aspects of previously described patients. MATERIALS AND METHODS: In the search for genetic aberrations in individuals with ID, two of the patients were identified by chromosomal microarray analysis, and five by exome sequencing. One of the individuals, suspected of MED13L-related intellectual disability, based on clinical features, was identified by Sanger sequencing. RESULTS: All 8 individuals had de novo MED13L aberrations, including two intragenic microdeletions, two frameshift, three nonsense variants, and one missense variant. Phenotypically, they all had intellectual disability, speech and motor delay, and features of the mouth (open mouth appearance, macroglossia, and/or macrostomia). Two individuals were diagnosed with autism, and one had autistic features. One had complex congenital heart defect, and one had persistent foramen ovale. The literature was reviewed with respect to clinical and dysmorphic features, and genetic aberrations. CONCLUSIONS: Even if most clinical features of MED13L-related intellectual disability are rather non-specific, the syndrome may be suspected in some individuals based on the association of developmental delay, speech impairment, bulbous nasal tip, and macroglossia, macrostomia, or open mouth appearance.

7.
Ugeskr Laeger ; 180(11)2018 Mar 12.
Artigo em Dinamarquês | MEDLINE | ID: mdl-29530238

RESUMO

KBG syndrome is a rare condition characterised by macrodontia of the upper central incisors, distinctive craniofacial findings, short stature, skeletal anomalies, and neurologic involvement including global developmental delay, seizures, and intellectual disability. This is a case report of a seven-year-old boy, who presented with symptoms fulfilling the diagnostic criteria of KBG syndrome, molecularly confirmed by detection of a heterozygous mutation in ANKRD11. To our knowledge, this is the first patient diagnosed with KBG syndrome in Denmark. The aim of this study is to raise awareness of this recognisable syndrome.

8.
Genet Med ; 20(9): 965-975, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29300384

RESUMO

PURPOSE: Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS. METHODS: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations. RESULTS: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations. CONCLUSION: Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.

10.
J Genet Couns ; 26(5): 1080-1089, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28265802

RESUMO

Outcome measurement in clinical genetics is challenging. Robust outcome measures are needed to provide evidence to support service development within genetic counseling. The Genetic Counselling Outcome Scale (GCOS-24), a Patient Reported Outcome Measure (PROM), was developed in English and validated with clinical genetics patients in the British NHS. This study reports the translation and adaptation of the GCOS-24 for use in Denmark. GCOS-24 was translated and back translated, supervised by an expert committee. Feedback on the first version was collected from genetic counseling patients in qualitative interviews focusing on instructions for use, response options and specific items considered semantically difficult. After further adjustment the adapted and translated version was administered to a second sample of patients, with responses analyzed using descriptive statistics. Eighteen interviews were conducted, and led to adjustment of item wording. Sixty-one patients completed the final version GCOS-24dk. Internal consistency is good (Cronbach's α =0.79), with an acceptable number of missing responses and no floor or ceiling effect observed. GCOS-24 has been successfully translated and adapted for use in a Danish setting. The study confirms the feasibility of local adaptation of patient reported outcome measures and stresses the importance of adaptation, even across quite similar populations and health care systems.


Assuntos
Aconselhamento Genético/normas , Inquéritos e Questionários/normas , Dinamarca , Feminino , Humanos , Masculino , Avaliação de Resultados (Cuidados de Saúde) , Psicometria , Reprodutibilidade dos Testes , Traduções
11.
Ugeskr Laeger ; 176(8A): V07130452, 2014 Feb 17.
Artigo em Dinamarquês | MEDLINE | ID: mdl-25350305

RESUMO

Although many congenital diseases present disturbances of the central nervous system, eyes and renal function, only few of these have a defined genetic basis. The first clinical features of cerebro-oculo-renal diseases usually develop in early childhood and deterioration of kidney function and even end-stage kidney disease may occur in a young age. The syndromes should be considered in patients with retarded growth and development, central nervous system abnormalities, impaired vision or blindness and progressive renal failure.


Assuntos
Síndrome Oculocerebrorrenal/genética , Anormalidades Múltiplas/genética , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/patologia , Doenças Cerebelares/genética , Cerebelo/anormalidades , Criança , Cílios/genética , Cílios/fisiologia , Transtornos da Motilidade Ciliar/genética , Ciliopatias , Encefalocele/genética , Anormalidades do Olho/genética , Predisposição Genética para Doença , Humanos , Doenças Renais Císticas/genética , Amaurose Congênita de Leber/genética , Atrofias Ópticas Hereditárias/genética , Doenças Renais Policísticas/genética , Retina/anormalidades , Retinite Pigmentosa
12.
Hum Mutat ; 31(4): 429-36, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20120035

RESUMO

Bardet-Biedl syndrome (BBS) is an autosomal recessive disease characterized by retinal dystrophy, polydactyly, obesity, learning disabilities, renal involvement, and male hypogenitalism. BBS is genetically heterogeneous with mutations of 14 genes, accounting for approximately 70% of cases. Triallelic inheritance has been suggested in about 5% of cases. Forty-nine unrelated BBS patients were screened for mutations by DHPLC analysis in BBS1, BBS2, BBS4, BBS6/MKKS, BBS10, and BBS12. The selected genes either account for more than 5% of the mutational load or are commonly reported in triallelic inheritance. Eight patients with only one or no BBS mutation were further investigated by single nucleotide polymorphism (SNP) analysis. In total, mutations were detected in 44 patients. Twenty percent had two mutations in BBS1, 18% in BBS2, 4% in BBS9, 43% in BBS10, and 2% in BBS12. Five patients were heterozygous for a sequence variation in BBS6/MKKS. We found eight patients with three sequence variations in two genes, which could be explained by triallelic inheritance, by the prevalence of heterozygous carriers or the third sequence variations representing rare polymorphisms. All changes found in a second BBS gene were amino acid substitutions. Genotype-phenotype correlations suggest a milder phenotype for BBS1 compared to BBS2 and BBS10, which we ascribe to the hypomorphic p.Met390Arg-mutation.


Assuntos
Síndrome de Bardet-Biedl/genética , Mutação/genética , Alelos , Sequência de Aminoácidos , Sequência de Bases , Sequência Conservada , Análise Mutacional de DNA , Dinamarca , Evolução Molecular , Feminino , Estudos de Associação Genética , Genótipo , Chaperoninas do Grupo II/química , Chaperoninas do Grupo II/genética , Humanos , Padrões de Herança/genética , Masculino , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único/genética
14.
Am J Med Genet A ; 143A(15): 1699-702, 2007 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-17587209

RESUMO

Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive disease with retinal dystrophy leading to blindness, postaxial polydactyly, truncal obesity, learning disabilities, male hypogenitalism, and renal anomalies. Heterozygous carriers of a BBS mutation are not thought to present symptoms of BBS; however, a previous study reported an increased risk of renal cancer among relatives of patients with BBS. This finding was based on the identification of three parents with renal cell carcinoma, representing a 17-fold increased risk. We performed a population-based study in Denmark to examine the incidence of cancer in 116 BBS patients and 428 relatives (96 families) through record linkage of information from files of the Retinitis Pigmentosa Registry, the Central Population Registry, and the Danish Cancer Registry. The clinical diagnosis of BBS was molecularly confirmed in 52% of the patients. Among the patients, two cancers were reported, with 4.3 expected. The cancers were an embryonal carcinoma of the testis in a 23-year-old man and an acoustic neuroma in a 51-year-old man. Among the relatives, 30 cancers were observed, with 45.2 expected. No renal cancers were observed in the two groups. These data do not support the suggested increased risk for renal cancer in relatives of patients with BBS.


Assuntos
Síndrome de Bardet-Biedl/genética , Neoplasias/genética , Dinamarca/epidemiologia , Família , Feminino , Humanos , Incidência , Masculino , Neoplasias/epidemiologia , Linhagem , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA