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1.
Hum Mutat ; 40(8): 1063-1070, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31045292

RESUMO

Microcephalic primordial dwarfism (MPD) is a group of rare single-gene disorders characterized by the extreme reduction in brain and body size from early development onwards. Proteins encoded by MPD-associated genes play important roles in fundamental cellular processes, notably genome replication and repair. Here we report the identification of four MPD individuals with biallelic variants in DNA2, which encodes an adenosine triphosphate (ATP)-dependent helicase/nuclease involved in DNA replication and repair. We demonstrate that the two intronic variants (c.1764-38_1764-37ins(53) and c.74+4A>C) found in these individuals substantially impair DNA2 transcript splicing. Additionally, we identify a missense variant (c.1963A>G), affecting a residue of the ATP-dependent helicase domain that is highly conserved between humans and yeast, with the resulting substitution (p.Thr655Ala) predicted to directly impact ATP/ADP (adenosine diphosphate) binding by DNA2. Our findings support the pathogenicity of these variants as biallelic hypomorphic mutations, establishing DNA2 as an MPD disease gene.

2.
BMC Pediatr ; 18(1): 308, 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30249237

RESUMO

BACKGROUND: Gillespie syndrome is a rare, congenital, neurological disorder characterized by the association of partial bilateral aniridia, non-progressive cerebellar ataxia and intellectual disability. Homozygous and heterozygous pathogenic variants of the ITPR1 gene encoding an inositol 1, 4, 5- triphosphate- responsive calcium channel have been identified in 13 patients recently. There have been 22 cases reported in the literature by 2016, mostly from the western hemisphere with none reported from Sri Lanka. CASE PRESENTATION: A 10-year-old girl born to healthy non-consanguineous parents with delayed development is described. She started walking unaided by 9 years with a significantly unsteady gait and her speech was similarly delayed. Physical examination revealed multiple cerebellar signs. Slit lamp examination of eyes revealed bilateral partial aniridia. Magnetic resonance imaging of brain at the age of 10 years revealed cerebellar (mainly vermian) hypoplasia. Genetic testing confirmed the clinical suspicion and demonstrated a heterozygous pathogenic variant c.7786_7788delAAG p.(Lys2596del) in the ITPR1 gene. CONCLUSION: The report of this child with molecular confirmation of Gillespie syndrome highlights the need for careful evaluation of ophthalmological and neurological features in patients that enables correct clinical diagnosis. The availability of genetic testing enables more accurate counseling of the parents and patients regarding recurrence risks to other family members.

4.
Genet Med ; 20(10): 1236-1245, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29323665

RESUMO

PURPOSE: We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10. METHODS: We retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-ß signaling with immunohistochemistry for pSMAD2 and CTGF. RESULTS: Stenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-ß signaling. CONCLUSION: Our findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.

5.
Genet Med ; 20(6): 599-607, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29236091

RESUMO

PurposeCopy-number variants (CNVs) are generally interpreted by linking the effects of gene dosage with phenotypes. The clinical interpretation of noncoding CNVs remains challenging. We investigated the percentage of disease-associated CNVs in patients with congenital limb malformations that affect noncoding cis-regulatory sequences versus genes sensitive to gene dosage effects.MethodsWe applied high-resolution copy-number analysis to 340 unrelated individuals with isolated limb malformation. To investigate novel candidate CNVs, we re-engineered human CNVs in mice using clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing.ResultsOf the individuals studied, 10% harbored CNVs segregating with the phenotype in the affected families. We identified 31 CNVs previously associated with congenital limb malformations and four novel candidate CNVs. Most of the disease-associated CNVs (57%) affected the noncoding cis-regulatory genome, while only 43% included a known disease gene and were likely to result from gene dosage effects. In transgenic mice harboring four novel candidate CNVs, we observed altered gene expression in all cases, indicating that the CNVs had a regulatory effect either by changing the enhancer dosage or altering the topological associating domain architecture of the genome.ConclusionOur findings suggest that CNVs affecting noncoding regulatory elements are a major cause of congenital limb malformations.


Assuntos
DNA Intergênico/genética , Deformidades Congênitas dos Membros/genética , Animais , Variações do Número de Cópias de DNA/genética , Feminino , Dosagem de Genes/genética , Genoma Humano , Estudo de Associação Genômica Ampla , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Linhagem , Fenótipo
6.
Am J Hum Genet ; 99(1): 125-38, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27374770

RESUMO

DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis.


Assuntos
Proteínas de Ciclo Celular/genética , Microtia Congênita/genética , Craniossinostoses/genética , Transtornos do Crescimento/genética , Micrognatismo/genética , Mutação , Patela/anormalidades , Adolescente , Adulto , Alelos , Processamento Alternativo/genética , Sequência de Aminoácidos , Âmnio/citologia , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/deficiência , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Células Cultivadas , Criança , Pré-Escolar , Análise Mutacional de DNA , Replicação do DNA , Exoma/genética , Éxons/genética , Feminino , Estudos de Associação Genética , Humanos , Masculino , Modelos Moleculares , Conformação Proteica , Síndrome , Adulto Jovem
7.
Am J Med Genet A ; 170A(5): 1216-24, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26789649

RESUMO

The 3MC syndromes are a group of rare autosomal recessive disorders where the main clinical features are cleft lip and palate, hypertelorism, highly arched eyebrows, caudal appendage, postnatal growth deficiency, and genitourinary tract anomalies. Ophthalmological abnormalities, most notably anterior chamber defects may also be seen. We describe the clinical and molecular findings in 13 individuals with suspected 3MC syndrome from 12 previously unreported families. The exclusion of the MASP1 and COLEC11 Loci in two individuals from different consanguineous families and the absence of mutations in four further individuals sequenced for both genes raises the possibility that that there is further genetic heterogeneity of 3MC syndrome.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Colectinas/genética , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Adolescente , Criança , Pré-Escolar , Fenda Labial/fisiopatologia , Fissura Palatina/fisiopatologia , Anormalidades do Olho/genética , Anormalidades do Olho/fisiopatologia , Face/anormalidades , Face/fisiopatologia , Feminino , Humanos , Hipertelorismo/genética , Hipertelorismo/fisiopatologia , Lactente , Masculino , Mutação , Análise de Sequência , Anormalidades Urogenitais/genética , Anormalidades Urogenitais/fisiopatologia
8.
J Med Genet ; 50(9): 585-92, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23812909

RESUMO

BACKGROUND: Harstfield syndrome is the rare and unique association of holoprosencephaly (HPE) and ectrodactyly, with or without cleft lip and palate, and variable additional features. All the reported cases occurred sporadically. Although several causal genes of HPE and ectrodactyly have been identified, the genetic cause of Hartsfield syndrome remains unknown. We hypothesised that a single key developmental gene may underlie the co-occurrence of HPE and ectrodactyly. METHODS: We used whole exome sequencing in four isolated cases including one case-parents trio, and direct Sanger sequencing of three additional cases, to investigate the causative variants in Hartsfield syndrome. RESULTS: We identified a novel FGFR1 mutation in six out of seven patients. Affected residues are highly conserved and are located in the extracellular binding domain of the receptor (two homozygous mutations) or the intracellular tyrosine kinase domain (four heterozygous de novo variants). Strikingly, among the six novel mutations, three are located in close proximity to the ATP's phosphates or the coordinating magnesium, with one position required for kinase activity, and three are adjacent to known mutations involved in Kallmann syndrome plus other developmental anomalies. CONCLUSIONS: Dominant or recessive FGFR1 mutations are responsible for Hartsfield syndrome, consistent with the known roles of FGFR1 in vertebrate ontogeny and conditional Fgfr1-deficient mice. Our study shows that, in humans, lack of accurate FGFR1 activation can disrupt both brain and hand/foot midline development, and that FGFR1 loss-of-function mutations are responsible for a wider spectrum of clinical anomalies than previously thought, ranging in severity from seemingly isolated hypogonadotropic hypogonadism, through Kallmann syndrome with or without additional features, to Hartsfield syndrome at its most severe end.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Dedos/anormalidades , Deformidades Congênitas da Mão/genética , Holoprosencefalia/genética , Mutação INDEL/genética , Deficiência Intelectual/genética , Deformidades Congênitas dos Membros/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Sequência de Bases , Sítios de Ligação , Fenda Labial/enzimologia , Fissura Palatina/enzimologia , Exoma , Feminino , Genômica , Deformidades Congênitas da Mão/enzimologia , Holoprosencefalia/enzimologia , Humanos , Deficiência Intelectual/enzimologia , Deformidades Congênitas dos Membros/enzimologia , Masculino , Modelos Moleculares , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/química , Análise de Sequência de DNA
9.
Am J Hum Genet ; 92(5): 792-9, 2013 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-23602711

RESUMO

The genetic cause of GAPO syndrome, a condition characterized by growth retardation, alopecia, pseudoanodontia, and progressive visual impairment, has not previously been identified. We studied four ethnically unrelated affected individuals and identified homozygous nonsense mutations (c.262C>T [p.Arg88*] and c.505C>T [p.Arg169*]) or splicing mutations (c.1435-12A>G [p.Gly479Phefs*119]) in ANTXR1, which encodes anthrax toxin receptor 1. The nonsense mutations predictably trigger nonsense-mediated mRNA decay, resulting in the loss of ANTXR1. The transcript with the splicing mutation theoretically encodes a truncated ANTXR1 containing a neopeptide composed of 118 unique amino acids in its C terminus. GAPO syndrome's major phenotypic features, which include dental abnormalities and the accumulation of extracellular matrix, recapitulate those found in Antxr1-mutant mice and point toward an underlying defect in extracellular-matrix regulation. Thus, we propose that mutations affecting ANTXR1 function are responsible for this disease's characteristic generalized defect in extracellular-matrix homeostasis.


Assuntos
Alopecia/genética , Anodontia/genética , Cromossomos Humanos Par 2/genética , Matriz Extracelular/genética , Predisposição Genética para Doença/genética , Transtornos do Crescimento/genética , Homeostase/genética , Proteínas de Neoplasias/genética , Atrofias Ópticas Hereditárias/genética , Receptores de Superfície Celular/genética , Alopecia/patologia , Processamento Alternativo/genética , Anodontia/patologia , Sequência de Bases , Códon sem Sentido/genética , Primers do DNA/genética , Matriz Extracelular/metabolismo , Fibroblastos , Imunofluorescência , Frequência do Gene , Transtornos do Crescimento/patologia , Humanos , Masculino , Dados de Sequência Molecular , Atrofias Ópticas Hereditárias/patologia , Linhagem , Sítios de Splice de RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
10.
Hum Mutat ; 34(4): 587-94, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23316014

RESUMO

Missense mutations affecting membrane-bound transcription factor protease site 2 (MBTPS2) have been associated with Ichthyosis Follicularis with Atrichia and Photophobia (IFAP) syndrome with or without BRESHECK syndrome, with keratosis follicularis spinulosa decalvans, and Olmsted syndrome. This metalloprotease activates, by intramembranous trimming in conjunction with the protease MBTPS1, regulatory factors involved in sterol control of transcription and in cellular stress response. In this study, 11 different MBTPS2 missense mutations detected in patients from 13 unrelated families were correlated with the clinical phenotype, with their effect on cellular growth in media without lipids, and their potential role for sterol control of transcription. Seven variants were novel [c.774C>G (p.I258M); c.758G>C (p.G253A); c.686T>C (p.F229S); c.1427T>C (p.L476S); c.1430A>T (p.D477V); c.1499G>A (p.G500D); c.1538T>C (p.L513P)], four had previously been reported in unrelated sibships [c.261G>A (p.M87I); c.1286G>A (p.R429H); c.1424T>C (p.F475S); c.1523A>G (p.N508S)]. In the enzyme, the mutations cluster in transmembrane domains. Amino-acid exchanges near the active site are more detrimental to functionality of the enzyme and, clinically, associated with more severe phenotypes. In male patients, a genotype-phenotype correlation begins to emerge, linking the site of the mutation in MBTPS2 with the clinical outcome described as IFAP syndrome with or without BRESHECK syndrome, keratosis follicularis spinulosa decalvans, X-linked, Olmsted syndrome, or possibly further X-linked traits with an oculocutaneous component.


Assuntos
Alopecia/genética , Estudos de Associação Genética , Ictiose/genética , Metaloendopeptidases/genética , Mutação de Sentido Incorreto , Fotofobia/genética , Adolescente , Alelos , Alopecia/diagnóstico , Animais , Linhagem Celular , Criança , Pré-Escolar , Feminino , Teste de Complementação Genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Ictiose/diagnóstico , Masculino , Metaloendopeptidases/química , Metaloendopeptidases/metabolismo , Repetições de Microssatélites , Fenótipo , Fotofobia/diagnóstico , Polimorfismo de Nucleotídeo Único , Transporte Proteico , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/genética , Adulto Jovem
11.
Eur J Hum Genet ; 20(4): 381-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22126750

RESUMO

MLL2 mutations are detected in 55 to 80% of patients with Kabuki syndrome (KS). In 20 to 45% patients with KS, the genetic basis remains unknown, suggesting possible genetic heterogeneity. Here, we present the largest yet reported cohort of 116 patients with KS. We identified MLL2 variants in 74 patients, of which 47 are novel and a majority are truncating. We show that pathogenic missense mutations were commonly located in exon 48. We undertook a systematic facial KS morphology study of patients with KS at our regional dysmorphology meeting. Our data suggest that nearly all patients with typical KS facial features have pathogenic MLL2 mutations, although KS can be phenotypically variable. Furthermore, we show that MLL2 mutation-positive KS patients are more likely to have feeding problems, kidney anomalies, early breast bud development, joint dislocations and palatal malformations in comparison with MLL2 mutation-negative patients. Our work expands the mutation spectrum of MLL2 that may help in better understanding of this molecule, which is important in gene expression, epigenetic control of active chromatin states, embryonic development and cancer. Our analyses of the phenotype indicates that MLL2 mutation-positive and -negative patients differ systematically, and genetic heterogeneity of KS is not as extensive as previously suggested. Moreover, phenotypic variability of KS suggests that MLL2 testing should be considered even in atypical patients.


Assuntos
Anormalidades Múltiplas/genética , Proteínas de Ligação a DNA/genética , Heterogeneidade Genética , Doenças Hematológicas/genética , Mutação , Proteínas de Neoplasias/genética , Fenótipo , Doenças Vestibulares/genética , Estudos de Coortes , Face/anormalidades , Feminino , Humanos , Análise de Sequência de DNA
12.
Ann Maxillofac Surg ; 2(2): 121-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23483617

RESUMO

BACKGROUND: Cleft palate is the commonest multifactorial epigenetic disorder with a prevalence of 0.43-2.45 per 1000. The objectives of this study were to evaluate the clinical features and identify the 22q11.2 deletion in patients with cleft palate in Sri Lanka. MATERIALS AND METHODS: Cleft patients attending a Teaching Hospital in Sri Lanka were recruited for this study. The relevant data were obtained from review of case notes, interviews, and examination of patients according to a standard evaluation sheet. Quantitative multiplex polymerase chain reaction (PCR) was performed to identify the 22q11.2 deletion. A gel documentation system (Bio-Doc) was used to quantify the PCR product following electrophoresis on 0.8% agarose gel. RESULTS AND CONCLUSION: There were 162 cleft palate patients of whom 59% were females. A total of 92 cleft palate subjects (56.2%) had other associated clinical features. Dysmorphic features (25.27%) and developmental delays (25.27%) were the commonest medical problems encountered. The cleft was limited to the soft palate in 125 patients, while in 25 patients it involved both the hard and the soft palate. There were seven subjects with bifid uvula and five subjects with submucous cleft palate. None of the patients had 22q11.2 deletion in this study population. A multicentered large population-based study is needed to confirm the results of this study and to develop guidelines on the appropriate use of 22q11.2 deletion testing, which are valid for cleft palate patients in Sri Lanka.

13.
Prenat Diagn ; 28(8): 715-21, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18561288

RESUMO

OBJECTIVES: Assess attitudes toward prenatal diagnosis (PND) and termination of pregnancy (TOP) for Down syndrome (DS), hemophilia, lethal autosomal recessive disorder (LRD) and a hypothetical late-onset neurodegenerative disorder (NDD) among healthcare workers in one Sri Lankan district. METHODS: Self-administered questionnaire (tested for content validity) completed by medical (n = 218) and nursing (n = 368) students, nurses (n = 178) and doctors (n = 127). RESULTS: Acceptability of PND was 94%, 91%, 86% and 71% respectively for LRD, DS, hemophilia and NDD. Favorable attitudes toward TOP for DS (84%), and LRD (82%) were higher compared with hemophilia (65%) and NDD (53%). There was willingness to consider TOP for self/spouse for DS (79%), LRD (78%), hemophilia (60%) and NDD (54%). The proportions willing to participate in a pregnancy termination (DS 54%, LRD 51%, hemophilia 38%, NDD 38%) were lower. Religious affiliation influenced attitudes regarding TOP with Christians being more opposed than Buddhists. CONCLUSIONS: There is acceptance of and willingness to participate in TOP for fetal anomalies among Sri Lankan healthcare workers. These findings have relevance for developing prenatal diagnostic services in Sri Lanka. Religious affiliation among Asian doctors, nurses (and patients) in developed countries is likely to determine permissiveness toward PND and TOP.


Assuntos
Aborto Induzido/psicologia , Atitude do Pessoal de Saúde , Doenças Genéticas Inatas/diagnóstico , Diagnóstico Pré-Natal/psicologia , Adulto , Feminino , Humanos , Masculino , Enfermeiras e Enfermeiros/psicologia , Médicos/psicologia , Sri Lanka , Estudantes de Medicina/psicologia , Estudantes de Enfermagem/psicologia , Inquéritos e Questionários
14.
Ceylon Med J ; 52(3): 95-100, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18020028

RESUMO

The adrenal glands secrete hormones essential for metabolism, regulation of blood pressure, and sodium and glucose homeostasis. Hypo- or hypersecretion of these hormones is life threatening. Understanding the physiological functions of adrenal hormones is a prerequisite to the management of adrenal gland disease.


Assuntos
Corticosteroides/biossíntese , Doenças das Glândulas Suprarrenais/fisiopatologia , Glândulas Suprarrenais/fisiologia , Hormônio Adrenocorticotrópico , Aldosterona/biossíntese , Glucocorticoides/biossíntese , Humanos
15.
Ceylon Med J ; 52(3): 100-3, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18020029

RESUMO

Adrenal insufficiency can be due to disease of the adrenal gland itself (primary adrenal deficiency) or of the hypothalamic or pituitary regulation of the adrenal gland (secondary adrenal insufficiency). This article discusses its causes, clinical features, diagnosis and treatment.


Assuntos
Doenças das Glândulas Suprarrenais/fisiopatologia , Glândulas Suprarrenais/fisiologia , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/etiologia , Glucocorticoides/uso terapêutico , Humanos , Mineralocorticoides/uso terapêutico
16.
Ceylon Med J ; 52(3): 104-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18020030

RESUMO

Hypersecretion from the adrenal glands is associated with hypertension. Causes include Conn syndrome, Cushing syndrome and phaechromocytoma. This article discusses their clinical features, diagnosis and treatment as well as the management of incidentally identified adrenal tumours (incidentaloma).


Assuntos
Glândulas Suprarrenais/fisiologia , Síndrome de Cushing/fisiopatologia , Hiperaldosteronismo/fisiopatologia , Doenças das Glândulas Suprarrenais/fisiopatologia , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/tratamento farmacológico , Humanos , Hiperaldosteronismo/tratamento farmacológico , Segunda Neoplasia Primária/fisiopatologia , Feocromocitoma/fisiopatologia
18.
Ceylon Med J ; 49(1): 18-20, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15255323

RESUMO

Genetic testing for single gene disorders is becoming available in Sri Lanka. While it offers many benefits, there are concerns about psychological and social problems that can be a consequence of such tests. This article aims to review the potential benefits and disadvantages of genetic testing, and recommends mechanisms that would help minimise problems associated with the inappropriate use of genetic tests.


Assuntos
Doenças Genéticas Inatas/diagnóstico , Confidencialidade , Feminino , Doenças Fetais/diagnóstico , Aconselhamento Genético , Humanos , Preconceito
19.
Twin Res ; 6(1): 67-71, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12626231

RESUMO

The National Twin Registry of Sri Lanka was established in 1997 as a volunteer register. To extend it to a population-based register, we examined the effectiveness of tracing older twins by inspecting birth records and recruiting them by postal invitation and in-person contact. Birth records at a divisional secretariat reported from 2 maternity hospitals between the years of 1954-1970 were scrutinised to identify a random sample of twins. These hospitals had the highest twin delivery rates for the whole country. We identified 620 twins and a questionnaire was mailed to them. Research assistants visited a cohort of non-respondents (71) in the postal survey. These 620 twins were identified after perusing 20700 birth records. The twinning rate was estimated at 29.95 ([620/20700] x 1000) twins per 1000 registered births (CI 27.63-32.27). In the postal survey, 37 (12%) responded and 62 letters were returned (20%). Both twins were still alive in 20 pairs, one was still alive in 15 pairs, and both twins were dead in 2 pairs. During field visits, 42 (59.2%) addresses were located. Information was available on 16 twin pairs. Both twins were alive in 8 pairs, one each in 4 pairs, and both were dead in 4 pairs and at least one twin was traced in 10 pairs (14%). Both the postal and the field survey gave a low yield. This finding is different from tracing younger twins born between 1985-1997 by using the same methods. Migration, urbanization and development in the country might have affected tracing older twins from the birth record addresses, which were decades old.


Assuntos
Sistema de Registros , Gêmeos , Declaração de Nascimento , Humanos , Sri Lanka , Inquéritos e Questionários
20.
Twin Res ; 5(5): 424-6, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12537869

RESUMO

Sri Lanka is an island with genetic diversity between the five main population groups. Our twin registry is the first in the developing world. Initially, we established a volunteer cohort of 4600 twin pairs through a competition advertised in the media. In addition, we have volunteer cohorts, birth registration-based cohorts through hospitals, and community-based cohorts. There is also a nationwide population-based younger twin cohort (1992-1997) traced through the Department of Birth and Death Registration. Additionally, we have adapted a Zygosity determination questionnaire and validated it. Establishing ethical guidelines for twin research was a priority because the field of bio-ethics is at an early stage of development in Sri Lanka. These guidelines were from a developing world perspective. A sister organization, the Multiple Birth Foundation, was formed to cater to twins and their special needs and to represent their interests, and several branches have been formed. We intend to build capacity by establishing a genetic lab and through crosscultural collaboration. Our vision is to establish a multidisciplinary research foundation. Based on our research findings, we plan to build services to cater to needs of twins by working with professionals, statutory services and government policy makers.


Assuntos
Estudos de Coortes , Sistema de Registros , Estudos em Gêmeos como Assunto/métodos , Gêmeos , Declaração de Nascimento , Atestado de Óbito , Países em Desenvolvimento , Ética Médica , Feminino , Variação Genética/genética , Humanos , Masculino , Defesa do Paciente , Vigilância da População/métodos , Guias de Prática Clínica como Assunto , Sistema de Registros/estatística & dados numéricos , Sri Lanka , Inquéritos e Questionários , Estudos em Gêmeos como Assunto/estatística & dados numéricos , Gêmeos/genética , Gêmeos/psicologia , Gêmeos/estatística & dados numéricos
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