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1.
Am J Hum Genet ; 105(2): 403-412, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31303265

RESUMO

POU3F3, also referred to as Brain-1, is a well-known transcription factor involved in the development of the central nervous system, but it has not previously been associated with a neurodevelopmental disorder. Here, we report the identification of 19 individuals with heterozygous POU3F3 disruptions, most of which are de novo variants. All individuals had developmental delays and/or intellectual disability and impairments in speech and language skills. Thirteen individuals had characteristic low-set, prominent, and/or cupped ears. Brain abnormalities were observed in seven of eleven MRI reports. POU3F3 is an intronless gene, insensitive to nonsense-mediated decay, and 13 individuals carried protein-truncating variants. All truncating variants that we tested in cellular models led to aberrant subcellular localization of the encoded protein. Luciferase assays demonstrated negative effects of these alleles on transcriptional activation of a reporter with a FOXP2-derived binding motif. In addition to the loss-of-function variants, five individuals had missense variants that clustered at specific positions within the functional domains, and one small in-frame deletion was identified. Two missense variants showed reduced transactivation capacity in our assays, whereas one variant displayed gain-of-function effects, suggesting a distinct pathophysiological mechanism. In bioluminescence resonance energy transfer (BRET) interaction assays, all the truncated POU3F3 versions that we tested had significantly impaired dimerization capacities, whereas all missense variants showed unaffected dimerization with wild-type POU3F3. Taken together, our identification and functional cell-based analyses of pathogenic variants in POU3F3, coupled with a clinical characterization, implicate disruptions of this gene in a characteristic neurodevelopmental disorder.

2.
Am J Hum Genet ; 103(2): 305-316, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30057029

RESUMO

Next-generation sequencing combined with international data sharing has enormously facilitated identification of new disease-associated genes and mutations. This is particularly true for genetically extremely heterogeneous entities such as neurodevelopmental disorders (NDDs). Through exome sequencing and world-wide collaborations, we identified and assembled 20 individuals with de novo variants in FBXO11. They present with mild to severe developmental delay associated with a range of features including short (4/20) or tall (2/20) stature, obesity (5/20), microcephaly (4/19) or macrocephaly (2/19), behavioral problems (17/20), seizures (5/20), cleft lip or palate or bifid uvula (3/20), and minor skeletal anomalies. FBXO11 encodes a member of the F-Box protein family, constituting a subunit of an E3-ubiquitin ligase complex. This complex is involved in ubiquitination and proteasomal degradation and thus in controlling critical biological processes by regulating protein turnover. The identified de novo aberrations comprise two large deletions, ten likely gene disrupting variants, and eight missense variants distributed throughout FBXO11. Structural modeling for missense variants located in the CASH or the Zinc-finger UBR domains suggests destabilization of the protein. This, in combination with the observed spectrum and localization of identified variants and the lack of apparent genotype-phenotype correlations, is compatible with loss of function or haploinsufficiency as an underlying mechanism. We implicate de novo missense and likely gene disrupting variants in FBXO11 in a neurodevelopmental disorder with variable intellectual disability and various other features.

3.
Hum Mutat ; 39(7): 1014-1023, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29688601

RESUMO

The role of disturbed chromatin remodeling in the pathogenesis of intellectual disability (ID) is well established and illustrated by de novo mutations found in a plethora of genes encoding for proteins of the epigenetic regulatory machinery. We describe mutations in the "SET nuclear proto-oncogene" (SET), encoding a component of the "inhibitor of histone acetyltransferases" (INHAT) complex, involved in transcriptional silencing. Using whole exome sequencing, four patients were identified with de novo mutations in the SET gene. Additionally, an affected mother and child were detected who carried a frameshift variant in SET. Four patients were found in literature. The de novo mutations in patients affected all four known SET mRNA transcripts. LoF mutations in SET are exceedingly rare in the normal population and, if present, affect only one transcript. The pivotal role of SET in neurogenesis is evident from in vitro and animal models. SET interacts with numerous proteins involved in histone modification, including proteins encoded by known autosomal dominant ID genes, that is, EP300, CREBBP, SETBP1, KMT2A, RAC1, and CTCF. Our study identifies SET as a new component of epigenetic regulatory modules underlying human cognitive disorders, and as a first member of the Nucleosome Assembly Protein (NAP) family implicated in ID.

4.
Am J Med Genet A ; 167A(9): 1983-92, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26033782

RESUMO

Robin sequence (RS) can be defined as the combination of micrognathia and upper airway obstruction/glossoptosis causing neonatal respiratory problems, with or without a cleft palate and either isolated or non-isolated. Pathogenesis varies widely. We hypothesize that optimal treatment depends on pathogenesis and therefore patients should be stratified according to diagnosis. Here, we evaluate diagnoses and (presumed) pathogeneses in an RS cohort. Medical records of all RS patients presenting between 1995-2013 in three academic hospitals were evaluated. Four clinical geneticists re-evaluated all information, including initial diagnosis. Diagnoses were either confirmed, considered uncertain, or rejected. If uncertain or rejected, patients were re-evaluated. Subsequent results were re-discussed and a final conclusion was drawn. We included 191 RS patients. After re-evaluation and changing initial diagnoses in 48 of the 191 patients (25.1%), 37.7% of the cohort had isolated RS, 8.9% a chromosome anomaly, 29.3% a Mendelian disorder, and 24.1% no detectable cause. Twenty-two different Mendelian disorders were diagnosed, of which Stickler syndrome was most frequent. Stratification of diagnoses according to (presumed) pathogenic mechanism in 73 non-isolated patients with reliable diagnoses showed 43.9% to have a connective tissue dysplasia, 5.5% a neuromuscular disorder, 47.9% a multisystem disorder, and 2.7% an unknown mechanism. We diagnosed more non-isolated RS patients compared to other studies. Re-evaluation changed initial diagnosis in a quarter of patients. We suggest standardized re-evaluation of all RS patients. Despite the relatively high diagnostic yield pathogenesis could be determined in only 59.7% (71/119), due to limited insight in pathogenesis in diagnosed entities. Further studies into pathogenesis of entities causing RS are indicated.


Assuntos
Síndrome de Pierre Robin/etiologia , Síndrome de Pierre Robin/patologia , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/patologia , Artrite/etiologia , Artrite/patologia , Fissura Palatina/patologia , Doenças do Tecido Conjuntivo/etiologia , Doenças do Tecido Conjuntivo/patologia , Feminino , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/patologia , Humanos , Masculino , Micrognatismo/etiologia , Micrognatismo/patologia , Descolamento Retiniano/etiologia , Descolamento Retiniano/patologia
5.
Prenat Diagn ; 35(6): 598-604, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25693726

RESUMO

OBJECTIVE: The aim of the study is to study pregnant women's views on noninvasive prenatal testing (NIPT) for Down syndrome and the potential to test for a broader range of conditions. METHODS: An online questionnaire available on the Dutch pregnancy fair website was completed by 381 pregnant women. RESULTS: Of the women, 51% expressed interest in having NIPT, including 33% of women who had declined first-trimester screening. The majority (73%) thought that the uptake of screening would increase with NIPT. Most women agreed that testing for life-threatening (89%), severe physical (79%), or severe mental (76%) disorders should be offered. A minority (29%) felt that prenatal screening should also be offered for late-onset disorders. Most (41%) preferred to have a free choice from a list of disorders, 31% preferred a 'closed offer', and 26% preferred choosing between packages of disorders. Although most women (76%) thought that screening for a broad range of conditions would avoid much suffering, 39% feared that it would confront couples with choices, the implications of which would be difficult to grasp. CONCLUSION: The results suggest that the uptake of screening will increase with NIPT. If NIPT will be offered for a broad range of conditions, it is crucial to find a way that facilitates rather than undermines well-informed decision-making.


Assuntos
Atitude Frente a Saúde , DNA/sangue , Síndrome de Down/diagnóstico , Gestantes/psicologia , Diagnóstico Pré-Natal/psicologia , Adulto , Feminino , Humanos , Países Baixos , Gravidez , Inquéritos e Questionários , Adulto Jovem
6.
Orphanet J Rare Dis ; 9: 53, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24735900

RESUMO

BACKGROUND: Segmental Xp22.2 monosomy or a heterozygous HCCS mutation is associated with the microphthalmia with linear skin defects (MLS) or MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome, an X-linked disorder with male lethality. HCCS encodes the holocytochrome c-type synthase involved in mitochondrial oxidative phosphorylation (OXPHOS) and programmed cell death. METHODS: We characterized the X-chromosomal abnormality encompassing HCCS or an intragenic mutation in this gene in six new female patients with an MLS phenotype by cytogenetic analysis, fluorescence in situ hybridization, sequencing, and quantitative real-time PCR. The X chromosome inactivation (XCI) pattern was determined and clinical data of the patients were reviewed. RESULTS: Two terminal Xp deletions of ≥ 11.2 Mb, two submicroscopic copy number losses, one of ~850 kb and one of ≥ 3 Mb, all covering HCCS, 1 nonsense, and one mosaic 2-bp deletion in HCCS are reported. All females had a completely (>98:2) or slightly skewed (82:18) XCI pattern. The most consistent clinical features were microphthalmia/anophthalmia and sclerocornea/corneal opacity in all patients and congenital linear skin defects in 4/6. Additional manifestations included various ocular anomalies, cardiac defects, brain imaging abnormalities, microcephaly, postnatal growth retardation, and facial dysmorphism. However, no obvious clinical sign was observed in three female carriers who were relatives of one patient. CONCLUSION: Our findings showed a wide phenotypic spectrum ranging from asymptomatic females with an HCCS mutation to patients with a neonatal lethal MLS form. Somatic mosaicism and the different ability of embryonic cells to cope with an OXPHOS defect and/or enhanced cell death upon HCCS deficiency likely underlie the great variability in phenotypes.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X/patologia , Microftalmia/patologia , Anormalidades da Pele/patologia , Pele/patologia , Criança , Pré-Escolar , Cromossomos Humanos X/genética , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Lactente , Microftalmia/genética , Anormalidades da Pele/genética , Inativação do Cromossomo X/genética
7.
Eur J Hum Genet ; 22(12): 1345-50, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24642832

RESUMO

Non-invasive prenatal testing (NIPT) and its potential to test for multiple disorders has received much attention. This study explores attitudes of women and men towards NIPT, and their views on widening the scope of prenatal testing in a country with a low uptake of prenatal screening (The Netherlands). Five focus groups with low-risk pregnant women (n=28), three focus groups with men (n=19) and 13 interviews with high- and low-risk pregnant women were conducted. Participants felt that current prenatal screening has great disadvantages such as uncertain results and risk of miscarriage from follow-up diagnostics. Characteristics of NIPT (accurate, safe and early testing) could therefore diminish these disadvantages of prenatal screening and help lower the barrier for participation. This suggests that NIPT might allow couples to decide about prenatal testing based mostly on their will to test or not, rather than largely based on fear of miscarriage risk or the uncertainty of results. The lower barrier for participation was also seen as a downside that could lead to uncritical use or pressure to test. Widening the scope of prenatal testing was seen as beneficial for severe disorders, although it was perceived difficult to determine where to draw the line. Participants argued that there should be a limit to the scope of NIPT, avoiding testing for minor abnormalities. The findings suggest that NIPT could enable more meaningful decision-making for prenatal screening. However, to ensure voluntary participation, especially when testing for multiple disorders, safeguards on the basis of informed decision-making will be of utmost importance.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Diagnóstico Pré-Natal/psicologia , Adulto , Tomada de Decisões , Síndrome de Down/diagnóstico , Estudos de Avaliação como Assunto , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Gravidez , Adulto Jovem
8.
J Clin Invest ; 122(11): 4003-11, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23093777

RESUMO

The HELLP syndrome is a pregnancy-associated disease inducing hemolysis, elevated liver enzymes, and low platelets in the mother. Although the HELLP symptoms occur in the third trimester in the mother, the origin of the disease can be found in the first trimester fetal placenta. A locus for the HELLP syndrome is present on chromosome 12q23 near PAH. Here, by multipoint nonparametric linkage, pedigree structure allele sharing, and haplotype association analysis of affected sisters and cousins, we demonstrate that the HELLP locus is in an intergenic region on 12q23.2 between PMCH and IGF1. We identified a novel long intergenic noncoding RNA (lincRNA) transcript of 205,012 bases with (peri)nuclear expression in the extravillous trophoblast using strand-specific RT-PCR complemented with RACE and FISH. siRNA-mediated knockdown followed by RNA-sequencing, revealed that the HELLP lincRNA activated a large set of genes that are involved in the cell cycle. Furthermore, blocking potential mutation sites identified in HELLP families decreased the invasion capacity of extravillous trophoblasts. This is the first large noncoding gene to be linked to a Mendelian disorder with autosomal-recessive inheritance.


Assuntos
Ciclo Celular/genética , Cromossomos Humanos Par 12 , Doenças Genéticas Inatas , Loci Gênicos , Síndrome HELLP , RNA Longo não Codificante , Trofoblastos/metabolismo , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 12/metabolismo , Família , Feminino , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/metabolismo , Doenças Genéticas Inatas/patologia , Estudo de Associação Genômica Ampla , Síndrome HELLP/genética , Síndrome HELLP/metabolismo , Síndrome HELLP/patologia , Humanos , Masculino , Linhagem , Gravidez , Primeiro Trimestre da Gravidez/genética , Primeiro Trimestre da Gravidez/metabolismo , Terceiro Trimestre da Gravidez/genética , Terceiro Trimestre da Gravidez/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Trofoblastos/patologia
9.
Eur J Hum Genet ; 18(9): 999-1005, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20531442

RESUMO

Holoprosencephaly is a severe malformation of the brain characterized by abnormal formation and separation of the developing central nervous system. The prevalence is 1:250 during early embryogenesis, the live-born prevalence is 1:16 000. The etiology of HPE is extremely heterogeneous and can be teratogenic or genetic. We screened four known HPE genes in a Dutch cohort of 86 non-syndromic HPE index cases, including 53 family members. We detected 21 mutations (24.4%), 3 in SHH, 9 in ZIC2 and 9 in SIX3. Eight mutations involved amino-acid substitutions, 7 ins/del mutations, 1 frame-shift, 3 identical poly-alanine tract expansions and 2 gene deletions. Pathogenicity of mutations was presumed based on de novo character, predicted non-functionality of mutated proteins, segregation of mutations with affected family-members or combinations of these features. Two mutations were reported previously. SNP array confirmed detected deletions; one spanning the ZIC2/ZIC5 genes (approx. 100 kb) the other a 1.45 Mb deletion including SIX2/SIX3 genes. The mutation percentage (24%) is comparable with previous reports, but we detected significantly less mutations in SHH: 3.5 vs 10.7% (P=0.043) and significantly more in SIX3: 10.5 vs 4.3% (P=0.018). For TGIF1 and ZIC2 mutation the rate was in conformity with earlier reports. About half of the mutations were de novo, one was a germ line mosaic. The familial mutations displayed extensive heterogeneity in clinical manifestation. Of seven familial index patients only two parental carriers showed minor HPE signs, five were completely asymptomatic. Therefore, each novel mutation should be considered as a risk factor for clinically manifest HPE, with the caveat of reduced clinical penetrance.


Assuntos
Proteínas do Olho/genética , Proteínas Hedgehog/genética , Holoprosencefalia/genética , Proteínas de Homeodomínio/genética , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Feminino , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único
10.
Eur J Hum Genet ; 17(12): 1560-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19550437

RESUMO

Autosomal recessive lethal and severe osteogenesis imperfecta (OI) is caused by the deficiency of cartilage-associated protein (CRTAP) and prolyl-3-hydroxylase 1 (P3H1) because of CRTAP and LEPRE1 mutations. We analyzed five families in which 10 individuals had a clinical diagnosis of lethal and severe OI with an overmodification of collagen type I on biochemical testing and without a mutation in the collagen type I genes. CRTAP mutations not described earlier were identified in the affected individuals. Although it seems that one important feature of autosomal recessive OI due to CRTAP mutations is the higher consistency of radiological features with OI type II-B/III, differentiation between autosomal dominant and autosomal recessive OI on the basis of clinical, radiological and biochemical investigations proves difficult in the affected individuals reported here. These observations confirm that once a clinical diagnosis of OI has been made in an affected individual, biochemical testing for overmodification of collagen type I should always be combined with molecular genetic analysis of the collagen type I genes. If no mutations in the collagen type I genes are found, additional molecular genetic analysis of the CRTAP and LEPRE1 genes should follow. This approach will allow proper identification of the genetic cause of lethal or severe OI, which is important in providing prenatal diagnosis, preimplantation genetic diagnosis and estimating recurrence risk.


Assuntos
Proteínas da Matriz Extracelular/genética , Biologia Molecular/métodos , Mutação/genética , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/patologia , Pré-Escolar , Análise Mutacional de DNA , Família , Evolução Fatal , Feminino , Feto/anormalidades , Feto/diagnóstico por imagem , Feto/patologia , Humanos , Recém-Nascido , Masculino , Osteogênese Imperfeita/diagnóstico por imagem , Linhagem , Gravidez , Radiografia
11.
Nat Genet ; 37(5): 514-9, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15806103

RESUMO

Preeclampsia is a pregnancy-associated disease with maternal symptoms but placental origin. Epigenetic inheritance is involved in some populations. By sequence analysis of 17 genes in the 10q22 region with maternal effects, we narrowed the minimal critical region linked with preeclampsia in the Netherlands to 444 kb. All but one gene in this region, which lies within a female-specific recombination hotspot, encode DNA- or RNA-binding proteins. One gene, STOX1 (also called C10orf24), contained five different missense mutations, identical between affected sisters, cosegregating with the preeclamptic phenotype and following matrilineal inheritance. Four STOX1 transcripts are expressed in early placenta, including invasive extravillus trophoblast, generating three different isoforms. All contain a winged helix domain related to the forkhead (FOX) family. The largest STOX1 isoform has exclusive nuclear or cytoplasmic expression, indicating activation and inactivation, respectively, of the PI3K-Akt-FOX pathway. Because all 38 FOX proteins and all 8 STOX1 homologs have either tyrosine or phenylalanine at position 153, the predominant Y153H variation is highly mutagenic by conservation criteria but subject to incomplete penetrance. STOX1 is a candidate for preeclampsia controlling polyploidization of extravillus trophoblast.


Assuntos
Cromossomos Humanos Par 10 , Pré-Eclâmpsia/genética , Transativadores/genética , Feminino , Fatores de Transcrição Forkhead , Haplótipos , Humanos , Masculino , Dados de Sequência Molecular , Família Multigênica , Linhagem , Gravidez , Análise de Sequência de DNA
12.
Mol Hum Reprod ; 10(8): 589-98, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15208369

RESUMO

By affected sib-pair linkage analysis of 24 families with pre-eclampsia, we confirm a susceptibility locus on chromosome 10q22.1 in Dutch females: a multipoint non-parametric linkage score of 3.6 near marker D10S1432 was obtained. Haplotype analysis showed a parent-of-origin effect: maximal allele sharing in the affected sibs was found for maternally derived alleles in all families, but not for the paternally derived alleles. As matrilineal inheritance suggests the presence of maternally expressed imprinted genes, while imprinting operates predominantly in (extra)embryonic tissues, all genes (n=132) known on 10q22 between GATA121A08 and D10S580 were screened for seven sequence-related features associated with imprinting and subsequently tested for expression in first trimester placenta. Placental expression of genes selected in this way (n=55) was compared with expression in androgenetic placentas of identical gestational age. Two regions on 10q22 were identified with developmentally co-repressed genes with non-random chromosomal distribution. Interestingly, these two clusters, near CTNNA3 and KCNMA1 and each containing five genes with down-regulated expression in androgenetic placentas, coincided with the regions with maximal maternal allele sharing seen in the pre-eclamptic sisters. Our linkage and expression data are compatible with the concept that pre-eclampsia involves maternally expressed imprinted genes that operate in the first trimester placenta.


Assuntos
Cromossomos Humanos Par 10/genética , Regulação da Expressão Gênica , Impressão Genômica , Placenta/metabolismo , Pré-Eclâmpsia/genética , Alelos , Animais , Epigênese Genética , Feminino , Ligação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Mola Hidatiforme/genética , Masculino , Camundongos , Linhagem , Gravidez
13.
Eur J Obstet Gynecol Reprod Biol ; 105(2): 94-113, 2002 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-12381470

RESUMO

Although there is substantial evidence that preeclampsia has a genetic background, the complexity of the processes involved and the fact that preeclampsia is a maternal-fetal phenomenon does not make the search for the molecular basis of preeclampsia genes easy. It is possible that the single phenotype 'preeclampsia' in fact should be divided into different sub-groups on genetic or biochemical level. In the present review, the preeclampsia phenotype and its pathophysiologic features are discussed. Family studies and postulated inheritance models are summarized. A systematic overview is given on the numerous candidate gene studies and gene-expression studies performed so far and on the currently available genome-wide scan data. Despite extensive research the molecular genetic basis of preeclampsia remains unclear. Future studies will hopefully enhance our insights in the molecular pathogenesis of preeclampsia.


Assuntos
Pré-Eclâmpsia/genética , Animais , Meio Ambiente , Feminino , Feto , Ligação Genética , Predisposição Genética para Doença , Hemodinâmica , Humanos , Modelos Genéticos , Estresse Oxidativo , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Trombofilia/genética
14.
Hypertens Pregnancy ; 21(1): 23-38, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12044341

RESUMO

OBJECTIVE: To determine whether preeclampsia is either associated with or linked to two polymorphisms in the IL1B gene (IL1B-TaqI and IL1B-511) and one polymorphism in the IL1RN gene (IL1RN-IVS2). METHODS: Genotyping was performed in 150 affected sib-pair families and 104 healthy Dutch blood donors. Genotype and allele frequencies as well as allelic associations were assessed in three groups of unrelated women from these 150 families; 133 with either eclampsia, preeclampsia or the haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, 101 with preeclampsia only, and 63 with HELLP syndrome only. These frequencies were compared to those in controls. Frequencies of transmitted and nontransmitted haplotypes, inferred from the three polymorphisms, were compared. Allele sharing between affected siblings from all 150 families was assessed by means of multipoint nonparametric affected sib-pair analyses. RESULTS: No significant differences in genotype and allele frequencies were found between the unrelated study groups and controls. No allelic associations were apparent, nor were there differences in frequencies of transmitted and nontransmitted haplotypes within affected families. Excess allele sharing for any of the three polymorphic markers was absent in affected sib-pairs. CONCLUSIONS: None of the IL1B and IL1RN polymorphisms provided evidence for either association or linkage with the risk for (pre)eclampsia/HELLP syndrome, preeclampsia only or HELLP syndrome only.


Assuntos
Ligação Genética/genética , Síndrome HELLP/genética , Interleucina-1/genética , Pré-Eclâmpsia/genética , Receptores de Interleucina-1/genética , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Polimorfismo Genético , Gravidez
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