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1.
Am J Hum Genet ; 105(5): 933-946, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31607427

RESUMO

Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands.

2.
Ann Hepatol ; 18(6): 862-868, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31635968

RESUMO

INTRODUCTION AND OBJECTIVES: Multidrug-resistant (MDR) infections in cirrhosis are associated with poor outcomes. We attempted a prospective study on infections in patients with cirrhosis evaluating microbiology of these infections and how outcomes depended on factors like bacterial resistance, appropriate antibiotics, stage of liver disease and whether outcomes were significantly different from patients who did not have infections. MATERIALS AND METHODS: This was a prospective evaluation involving one hundred and fifty nine patients with cirrhosis who were admitted at Peerless Hospitex Hospital and Research Center, Kolkata, West Bengal, India, during a 24 month period. One hundred and nineteen of these patients either had an infection at the time of admission or developed infection during hospitalization. Forty patients did not have an infection at admission and did not acquire infection while admitted. Data was collected about demographics, etiology of cirrhosis, liver and renal function and microbiology. RESULTS: Infections were community acquired in 27.7% of patients, healthcare associated in 52.9% and nosocomial in 19.3%. Gram negative bacilli (Escherichia coli 47.4% Klebsiella pneumoniae 23%) were common. 84.9% of enterobacteriaceae produced ESBL, AmpC or Carbapenemases. Spontaneous bacteria peritonitis (SBP) and urinary tract infection (UTI) were the most common sites of infection. In hospital mortality was 21.9%. Non-survivors had higher MELD (26 vs 19, p<0.001) and CTP scores (11.7 vs 10.3, p<0.001). The control group had lower MELD (16.65 vs. 20.8, p<0.001) and CTP scores (9.25 vs 10.59, p<0.001). CONCLUSIONS: MDR infections are common in patients with cirrhosis and have serious implications for treatment and outcomes.

3.
BMC Ophthalmol ; 19(1): 5, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30616677

RESUMO

BACKGROUND: It has been previously reported that one copy of the variable number tandem repeat (VNTR) B alleles of the GPIbα gene increases the risk of non-arteritic ischaemic optic neuropathy (NAION) and the second eye involvement. This is the first case where the presence of both alleles is associated with bilateral NAION. CASE PRESENTATION: A 52-year-old male presented with loss of vision in one eye and was diagnosed with NAION. The following year, he suffered another attack of NAION in the fellow eye. Genetic testing showed that he had both copies of VNTR B alleles of the GPIbα gene. CONCLUSIONS: We report a case of bilateral NAION in the presence of two copies of VNTR B alleles of the GPIbα gene. This may have further implications for the function of platelet glycoproteins.


Assuntos
Neuropatia Óptica Isquêmica/genética , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Alelos , Humanos , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites
4.
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.

5.
Am J Med Genet A ; 176(5): 1108-1114, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29383814

RESUMO

Variants in the Protein Kinase CK2 alpha subunit, encoding the CSNK2A1 gene, have previously been reported in children with an intellectual disability and dysmorphic facial features syndrome: now termed the Okur-Chung neurodevelopmental syndrome. More recently, through trio-based exome sequencing undertaken by the Deciphering Developmental Disorders Study (DDD study), a further 11 children with de novo CSNK2A1 variants have been identified. We have undertaken detailed phenotyping of these patients. Consistent with previously reported patients, patients in this series had apparent intellectual disability, swallowing difficulties, and hypotonia. While there are some shared facial characteristics, the gestalt is neither consistent nor readily recognized. Congenital heart abnormalities were identified in nearly 30% of the patients, representing a newly recognized CSNK2A1 clinical association. Based upon the clinical findings from this study and the previously reported patients, we suggest an initial approach to the management of patients with this recently described intellectual disability syndrome.

7.
Am J Hum Genet ; 101(5): 768-788, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29100089

RESUMO

Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration. For both CAMK2A and CAMK2B, we identified mutations that decreased or increased CAMK2 auto-phosphorylation at Thr286/Thr287. We further found that all mutations affecting auto-phosphorylation also affected neuronal migration, highlighting the importance of tightly regulated CAMK2 auto-phosphorylation in neuronal function and neurodevelopment. Our data establish the importance of CAMK2A and CAMK2B and their auto-phosphorylation in human brain function and expand the phenotypic spectrum of the disorders caused by variants in key players of the glutamatergic signaling pathway.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Deficiência Intelectual/genética , Mutação/genética , Animais , Encéfalo/patologia , Linhagem Celular , Exoma/genética , Feminino , Ácido Glutâmico/genética , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/patologia , Fosforilação/genética , Transdução de Sinais/genética
10.
Epilepsia ; 58(4): 565-575, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28166369

RESUMO

OBJECTIVE: The phenotype of seizure clustering with febrile illnesses in infancy/early childhood is well recognized. To date the only genetic epilepsy consistently associated with this phenotype is PCDH19, an X-linked disorder restricted to females, and males with mosaicism. The SMC1A gene, which encodes a structural component of the cohesin complex is also located on the X chromosome. Missense variants and small in-frame deletions of SMC1A cause approximately 5% of Cornelia de Lange Syndrome (CdLS). Recently, protein truncating mutations in SMC1A have been reported in five females, all of whom have been affected by a drug-resistant epilepsy, and severe developmental impairment. Our objective was to further delineate the phenotype of SMC1A truncation. METHOD: Female cases with de novo truncation mutations in SMC1A were identified from the Deciphering Developmental Disorders (DDD) study (n = 8), from postmortem testing of an affected twin (n = 1), and from clinical testing with an epilepsy gene panel (n = 1). Detailed information on the phenotype in each case was obtained. RESULTS: Ten cases with heterozygous de novo mutations in the SMC1A gene are presented. All 10 mutations identified are predicted to result in premature truncation of the SMC1A protein. All cases are female, and none had a clinical diagnosis of CdLS. They presented with onset of epileptic seizures between <4 weeks and 28 months of age. In the majority of cases, a marked preponderance for seizures to occur in clusters was noted. Seizure clusters were associated with developmental regression. Moderate or severe developmental impairment was apparent in all cases. SIGNIFICANCE: Truncation mutations in SMC1A cause a severe epilepsy phenotype with cluster seizures in females. These mutations are likely to be nonviable in males.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/genética , Epilepsia/genética , Mutação/genética , Convulsões/genética , Criança , Pré-Escolar , Eletroencefalografia , Epilepsia/complicações , Feminino , Heterozigoto , Humanos , Masculino , Convulsões/complicações
11.
Hum Mol Genet ; 26(3): 519-526, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28053047

RESUMO

Haploinsufficiency in DYRK1A is associated with a recognizable developmental syndrome, though the mechanism of action of pathogenic missense mutations is currently unclear. Here we present 19 de novo mutations in this gene, including five missense mutations, identified by the Deciphering Developmental Disorder study. Protein structural analysis reveals that the missense mutations are either close to the ATP or peptide binding-sites within the kinase domain, or are important for protein stability, suggesting they lead to a loss of the protein's function mechanism. Furthermore, there is some correlation between the magnitude of the change and the severity of the resultant phenotype. A comparison of the distribution of the pathogenic mutations along the length of DYRK1A with that of natural variants, as found in the ExAC database, confirms that mutations in the N-terminal end of the kinase domain are more disruptive of protein function. In particular, pathogenic mutations occur in significantly closer proximity to the ATP and the substrate peptide than the natural variants. Overall, we suggest that de novo dominant mutations in DYRK1A account for nearly 0.5% of severe developmental disorders due to substantially reduced kinase function.


Assuntos
Transtorno Autístico/genética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Transtorno Autístico/patologia , Deficiências do Desenvolvimento/fisiopatologia , Feminino , Haploinsuficiência/genética , Humanos , Deficiência Intelectual/patologia , Masculino , Mutação , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Conformação Proteica , Proteínas Serina-Treonina Quinases/química , Proteínas Tirosina Quinases/química , Relação Estrutura-Atividade
12.
Am J Hum Genet ; 98(5): 981-992, 2016 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-27108798

RESUMO

Gillespie syndrome (GS) is characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, and progressive cerebellar atrophy. Trio-based exome sequencing identified de novo mutations in ITPR1 in three unrelated individuals with GS recruited to the Deciphering Developmental Disorders study. Whole-exome or targeted sequence analysis identified plausible disease-causing ITPR1 mutations in 10/10 additional GS-affected individuals. These ultra-rare protein-altering variants affected only three residues in ITPR1: Glu2094 missense (one de novo, one co-segregating), Gly2539 missense (five de novo, one inheritance uncertain), and Lys2596 in-frame deletion (four de novo). No clinical or radiological differences were evident between individuals with different mutations. ITPR1 encodes an inositol 1,4,5-triphosphate-responsive calcium channel. The homo-tetrameric structure has been solved by cryoelectron microscopy. Using estimations of the degree of structural change induced by known recessive- and dominant-negative mutations in other disease-associated multimeric channels, we developed a generalizable computational approach to indicate the likely mutational mechanism. This analysis supports a dominant-negative mechanism for GS variants in ITPR1. In GS-derived lymphoblastoid cell lines (LCLs), the proportion of ITPR1-positive cells using immunofluorescence was significantly higher in mutant than control LCLs, consistent with an abnormality of nuclear calcium signaling feedback control. Super-resolution imaging supports the existence of an ITPR1-lined nucleoplasmic reticulum. Mice with Itpr1 heterozygous null mutations showed no major iris defects. Purkinje cells of the cerebellum appear to be the most sensitive to impaired ITPR1 function in humans. Iris hypoplasia is likely to result from either complete loss of ITPR1 activity or structure-specific disruption of multimeric interactions.


Assuntos
Aniridia/etiologia , Aniridia/patologia , Ataxia Cerebelar/etiologia , Ataxia Cerebelar/patologia , Genes Dominantes/genética , Receptores de Inositol 1,4,5-Trifosfato/genética , Deficiência Intelectual/etiologia , Deficiência Intelectual/patologia , Mutação/genética , Adolescente , Adulto , Animais , Células Cultivadas , Criança , Feminino , Humanos , Receptores de Inositol 1,4,5-Trifosfato/química , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Camundongos , Microscopia Confocal , Pessoa de Meia-Idade , Linhagem , Conformação Proteica
13.
Invest Ophthalmol Vis Sci ; 57(3): 1053-62, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26968735

RESUMO

PURPOSE: Mutations in the ciliary transporter gene IFT140, usually associated with a severe syndromic ciliopathy, may also cause isolated retinal dystrophy. A series of patients with nonsyndromic retinitis pigmentosa (RP) due to IFT140 was investigated in this study. METHODS: Five probands and available affected family members underwent detailed phenotyping including retinal imaging and electrophysiology. Whole exome sequencing was performed on two probands, a targeted sequencing panel of 176 retinal genes on a further two, and whole genome sequencing on the fifth. Missense mutations of IFT140 were further investigated in vitro using transient plasmid transfection of hTERT-RPE1 cells. RESULTS: Eight affected patients from five families had preserved visual acuity until at least the second decade; all had normal development without skeletal manifestations or renal failure at age 13 to 67 years (mean, 42 years; median, 44.5 years). Bi-allelic mutations in IFT140 were identified in all families including two novel mutations: c.2815T > C (p.Ser939Pro) and c.1422_23insAA (p.Arg475Asnfs*14). Expression studies demonstrated a significantly reduced number of cells showing localization of mutant IFT140 with the basal body for two nonsyndromic mutations and two syndromic mutations compared with the wild type and a polymorphism. CONCLUSIONS: This study highlights the phenotype of nonsyndromic RP due to mutations in IFT140 with milder retinal dystrophy than that associated with the syndromic disease.


Assuntos
Proteínas de Transporte/genética , Corpo Ciliar/metabolismo , DNA/genética , Mutação , Distrofias Retinianas/genética , Adolescente , Adulto , Idoso , Alelos , Proteínas de Transporte/metabolismo , Corpo Ciliar/patologia , Análise Mutacional de DNA , Exoma , Feminino , Angiofluoresceinografia , Fundo de Olho , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/metabolismo , Distrofias Retinianas/patologia , Adulto Jovem
15.
Lab Med ; 46(2): 146-9; quiz e31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25918194

RESUMO

Vitamin D toxicity also known as hypervitaminosis D was previously believed to be rare. But with an increase in vitamin D supplementation several cases have been reported in literature. Fat soluble vitamins like Vitamin D, due to their ability to accumulate in the body, have a higher potential for toxicity than water soluble vitamins. The main clinical consequence of vitamin D toxicity is hypercalcemia. In this report we describe an adult female patient who developed very high serum Vitamin D levels (746 ng/mL, RI: 20 to 50) as a result of medication error. Inspite of such high serum concentrations the patient was without any clinical symptoms and had normal serum calcium. We critically discuss the mechanism of toxicity and hypothesize the possible molecular/metabolic factors which might have been responsible for this nontoxic presentation. This case study highlights the fact that physicians need to consider the risk of medication errors while prescribing Vitamin D therapy. Clinical trials to study Vitamin D toxicity in humans is not possible ethically. Thus the evidence base regarding the safety profile of Vitamin D supplementation in humans has been build through case reports. This review of the paradoxical clinico-laboratory manifestation of hypervitaminosis D could possibly contribute to existing literature.


Assuntos
Hipercalcemia/induzido quimicamente , Vitamina D/efeitos adversos , Absorciometria de Fóton , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/dietoterapia , Proteínas de Ligação a DNA/metabolismo , Suplementos Nutricionais/efeitos adversos , Feminino , Seguimentos , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/fisiopatologia , Fatores de Transcrição/metabolismo
16.
J Expo Sci Environ Epidemiol ; 23(2): 156-62, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22990472

RESUMO

In the state of West Bengal in India, over 26 million individuals are exposed to arsenic via drinking water. Dermatological, non-dermatological disorders and cancers are associated with arsenic toxicity. Of late, there has been a decrease in the arsenic concentration in drinking water owing to governmental efforts, raising the possibility of remediation. A cross-sectional study was conducted, where 189 arsenicosis and 171 unexposed individuals were recruited at two time points, (2005-06 and 2010-11) with concomitant decrease in the level of arsenic exposure via drinking water in the arsenicosis group in 2010-11. Parameters studied included dermatological, non-dermatological health status and cytogenetic damage. Decrease of arsenic exposure (190.1 µg/l to 37.94 µg/l) resulted in significant decline in the number of individuals having dermatological disorders (P<0.01) and in the severity of each dermatological outcome (P<0.0001). Micronucleus formation in urothelial cells and lymphocytes decreased significantly (P<0.001). However, there was a significant (P<0.001) rise in the incidence of each of the non-dermatological diseases, that is, peripheral neuropathy, conjunctivitis and respiratory distress over the period. Thirteen (6.87%) of the initially recruited arsenicosis individuals died of cancer, in this period. Remediation by arsenic-safe drinking water can reduce dermatological manifestations and cytogenetic insult; but is unable to counter the non-dermatological symptoms.


Assuntos
Intoxicação por Arsênico/epidemiologia , Arsênico/toxicidade , Carcinógenos/toxicidade , Adulto , Testes de Carcinogenicidade , Estudos Transversais , Água Potável/química , Exposição Ambiental , Humanos , Índia/epidemiologia , Testes para Micronúcleos
17.
Biotechnol Bioeng ; 110(2): 609-18, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22903591

RESUMO

Cortical bone allografts suffer from high rates of failure due to poor integration with host tissue, leading to non-union, fracture, and infection following secondary procedures. Here, we report a method for modifying the surfaces of cortical bone with coatings that have biological functions that may help overcome these challenges. These chitosan-heparin coatings promote mesenchymal stem cell attachment and have significant antibacterial activity against both S. aureus and E. coli. Furthermore, their chemistry is similar to coatings we have reported on previously, which effectively stabilize and deliver heparin-binding growth factors. These coatings have potential as synthetic periosteum for improving bone allograft outcomes.


Assuntos
Materiais Biocompatíveis/química , Transplante Ósseo/métodos , Quitosana/química , Heparina/química , Células-Tronco Mesenquimais/citologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Células Cultivadas , Escherichia coli/efeitos dos fármacos , Ácidos Graxos , Feminino , Fêmur , Células-Tronco Mesenquimais/efeitos dos fármacos , Periósteo/química , Espectroscopia Fotoeletrônica , Ovinos , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície
18.
Pediatr Neurol ; 45(5): 347-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22000320

RESUMO

"Triple A" syndrome is a rare, autosomal recessive condition whose main clinical features are alacrima, achalasia, and adrenal failure. Most patients also develop some neurologic abnormalities. We describe an 11-year-old boy with triple A syndrome who presented with progressive axonal motor neuropathy. Molecular analysis revealed compound heterozygous mutations in the AAAS gene, confirming the clinical diagnosis. The clinical presentation of patients with triple A syndrome is variable. Our patient manifested neurologic problems during early childhood, before other features of this condition were apparent. We highlight the neurologic presentation of this multisystem disorder. In the presence of complex axonal neuropathy, other features of this condition should be sought.


Assuntos
Insuficiência Adrenal/complicações , Insuficiência Adrenal/diagnóstico , Acalasia Esofágica/complicações , Acalasia Esofágica/diagnóstico , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/diagnóstico , Criança , Humanos , Masculino , Exame Neurológico/métodos , Síndrome
19.
Toxicol Appl Pharmacol ; 249(1): 47-54, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20732340

RESUMO

Chronic arsenic exposure through contaminated drinking water is a major environmental health issue. Chronic arsenic exposure is known to exert its toxic effects by a variety of mechanisms, of which generation of reactive oxygen species (ROS) is one of the most important. A high level of ROS, in turn, leads to DNA damage that might ultimately culminate in cancer. In order to keep the level of ROS in balance, an array of enzymes is present, of which catalase (CAT) and myeloperoxidase (MPO) are important members. Hence, in this study, we determined the activities of these two enzymes in the sera and chromosomal aberrations (CA) in peripheral blood lymphocytes in individuals exposed and unexposed to arsenic in drinking water. Arsenic in drinking water and in urine was used as a measure of exposure. Our results show that individuals chronically exposed to arsenic have significantly higher CAT and MPO activities and higher incidence of CA. We found moderate positive correlations between CAT and MPO activities, induction of CA and arsenic in urine and water. These results indicate that chronic arsenic exposure causes higher CAT and MPO activities in serum that correlates with induction of genetic damage. We conclude that the serum levels of these enzymes might be used as biomarkers of early arsenic exposure induced disease much before the classical dermatological symptoms of arsenicosis begin to appear.


Assuntos
Intoxicação por Arsênico/sangue , Catalase/sangue , Aberrações Cromossômicas/induzido quimicamente , Exposição Ambiental , Peroxidase/sangue , Poluentes Químicos da Água/sangue , Adolescente , Adulto , Idoso , Intoxicação por Arsênico/enzimologia , Intoxicação por Arsênico/genética , Biomarcadores/sangue , Exposição Ambiental/efeitos adversos , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dermatopatias/sangue , Dermatopatias/enzimologia , Dermatopatias/etiologia , Fatores de Tempo , Poluentes Químicos da Água/efeitos adversos , Abastecimento de Água/análise , Adulto Jovem
20.
Am J Med Genet A ; 149A(8): 1628-40, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19606471

RESUMO

Nicolaides-Baraitser syndrome (NBS) is an infrequently described condition, thus far reported in five cases. In order to delineate the phenotype and its natural history in more detail, we gathered data on 18 hitherto unreported patients through a multi-center collaborative study, and follow-up data of the earlier reported patients. A detailed comparison of the 23 patients is provided. NBS is a distinct and recognizable entity, and probably has been underdiagnosed until now. Main clinical features are severe mental retardation with absent or limited speech, seizures, short stature, sparse hair, typical facial characteristics, brachydactyly, prominent finger joints and broad distal phalanges. Some of the features are progressive with time. The main differential diagnosis is Coffin-Siris syndrome. There is no important gender difference in occurrence and frequency of the syndrome, and all cases have been sporadic thus far. Microarray analysis performed in 14 of the patients gave normal results. Except for the progressive nature there are no clues to the cause.


Assuntos
Anormalidades Múltiplas/patologia , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Radiografia , Síndrome , Adulto Jovem
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