Abstract:
BACKGROUND:Mutations in the SLC26A4 gene are associated with Pendred syndrome and autosomal recessive non-syndromic deafness (DFNB4). Both disorders have similar audiologic characteristics: bilateral hearing loss, often severe or profound, which may be associated with abnormalities of the inner ear, such as dilatation of the vestibular aqueduct or Mondini dysplasia. But, in Pendred syndrome (OMIM #274600), with autosomal recessive inheritance, besides congenital sensorineural deafness, goiter or thyroid dysfunctions are frequently present. The aim of this study was to determine whether mutations in SLC26A4 are a frequent cause of hereditary deafness in Brazilian patients. METHODS:Microsatellite haplotypes linked to SLC26A4 were investigated in 68 families presenting autosomal recessive non-syndromic deafness. In the probands of the 16 families presenting segregation consistent with linkage to SLC26A4, Sanger sequencing of the 20 coding exons was performed. In an additional sample of 15 individuals with suspected Pendred syndrome, because of the presence of hypothyroidism or cochleovestibular malformations, the SLC26A4 gene coding region was also sequenced. RESULTS:In two of the 16 families with indication of linkage to SLC26A4, the probands were found to be compound heterozygotes for probably pathogenic different mutations: three novel (c.1003 T > G (p. F335 V), c.1553G > A (p.W518X), c.2235 + 2 T > C (IVS19 + 2 T > C), and one already described, c.84C > A (p.S28R). Two of the 15 individuals with suspected Pendred syndrome because of hypothyreoidism or cochleovestibular malformations were monoallelic for likely pathogenic mutations: a splice mutation (IVS7 + 2 T > C) and the previously described c.1246A > C (p.T416P). Pathogenic copy number variations were excluded in the monoallelic cases and in those with normal results after Sanger sequencing. Additional mutations in the SLC26A4 gene or other definite molecular cause for deafness were not identified in the monoallelic patients, after exome sequencing. CONCLUSIONS:Biallelic pathogenic mutations in SLC26A4 explained ~ 3% of cases selected because of autosomal recessive deafness. Monoallelic mutations were present in ~ 13% of isolated cases of deafness with cochleovestibular malformations or suspected Pendred syndrome. These data reinforce the importance of mutation screening of SLC26A4 in Brazilian subjects and highlight the elevated frequency of monoallelic patients.
journal_name
BMC Med Genetjournal_title
BMC medical geneticsauthors
Nonose RW,Lezirovitz K,de Mello Auricchio MTB,Batissoco AC,Yamamoto GL,Mingroni-Netto RCdoi
10.1186/s12881-018-0585-xsubject
Has Abstractpub_date
2018-05-08 00:00:00pages
73issue
1issn
1471-2350pii
10.1186/s12881-018-0585-xjournal_volume
19pub_type
杂志文章abstract:BACKGROUND:Progressive familial intrahepatic cholestasis (PFIC) type 3 is an autosomal recessive disorder arising from mutations in the ATP-binding cassette subfamily B member 4 (ABCB4) gene. This gene encodes multidrug resistance protein-3 (MDR3) that acts as a hepatocanalicular floppase that transports phosphatidylch...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01173-0
更新日期:2020-11-30 00:00:00
abstract:BACKGROUND:Methylenetetrahydrofolate reductase (MTHFR) has a major impact on the regulation of the folic acid pathway due to conversion of 5,10-methylenetetrahydrofolate (methylene-THF) to 5-methyl-THF. Two common polymorphisms (677C>T and 1298A>C) in the gene coding for MTHFR have been shown to reduce MTHFR enzyme act...
journal_title:BMC medical genetics
pub_type: 杂志文章,多中心研究
doi:10.1186/1471-2350-6-23
更新日期:2005-05-27 00:00:00
abstract:BACKGROUND:Rs189037 (G > A) is a functional single nucleotide polymorphism (SNP) in the Ataxia-telangiectasia mutated (ATM) gene that may be associated with the risk of cancer. We performed a meta-analysis to determine whether rs189037 polymorphism influences the occurrence of cancer and examined the relationship betwe...
journal_title:BMC medical genetics
pub_type: 杂志文章,meta分析
doi:10.1186/s12881-019-0760-8
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND:The goal of this study was to review relevant case-control studies to determine the association of tumor necrosis factor-α (TNF-α) gene polymorphisms and coronary artery disease (CAD) susceptibility. METHODS:Using appropriate keywords, we identified relevant studies using PubMed, Cochrane, Embase, CNKI, VAN...
journal_title:BMC medical genetics
pub_type: 杂志文章,meta分析
doi:10.1186/s12881-020-0952-2
更新日期:2020-02-11 00:00:00
abstract:BACKGROUND:Age at onset of Huntington's disease (HD) is correlated with the size of the abnormal CAG repeat expansion in the HD gene; however, several studies have indicated that other genetic factors also contribute to the variability in HD age at onset. To identify modifier genes, we recently reported a whole-genome ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-7-71
更新日期:2006-08-17 00:00:00
abstract:BACKGROUND:It is believed that hereditary hemochromatosis (HH) might play a role in cardiac disease (heart failure (HF) and ischemia). Mutations within several genes are HH-associated, the most common being the HFE gene. In a large cohort of HF patients, we sought to determine the etiological role and the prognostic si...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-11-117
更新日期:2010-07-29 00:00:00
abstract:BACKGROUND:Diabetes mellitus (DM) is divided into four different etiological categories: type 1 DM (T1DM), type 2 DM (T2DM), other specific types, and gestational DM. One severe complication of T2DM is type 2 diabetic nephropathy (T2DN). The possible association of serum transforming growth factor-β1 (TGF-β1) levels an...
journal_title:BMC medical genetics
pub_type: 杂志文章,meta分析
doi:10.1186/s12881-018-0717-3
更新日期:2018-11-20 00:00:00
abstract:BACKGROUND:Propionic acidemia (PA)(OMIM#606054) is an inborn error of branched-chain amino acid metabolism, caused by defects in the propionyl-CoA carboxylase (PCC) enzyme which encoded by the PCCA and PCCB genes. CASE PRESENTATION:Here we report a Chinese neonate diagnosed with suspected PA based on the clinical symp...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01102-1
更新日期:2020-08-20 00:00:00
abstract:BACKGROUND:Probably the best example of the rise and maintenance of balancing selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in protecting from malaria. Yet, the dynamics of such a process remains poorly understood, particularly in relation to different malaria transmission rates and the ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-11-21
更新日期:2010-02-03 00:00:00
abstract:BACKGROUND:Amelogenesis imperfecta (AI) is a highly heterogeneous group of hereditary developmental abnormalities which mainly affects the dental enamel during tooth development in terms of its thickness, structure, and composition. It appears both in syndromic as well as non-syndromic forms. In the affected individual...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01038-6
更新日期:2020-05-07 00:00:00
abstract:BACKGROUND:Bilateral posterior periventricular nodular heterotopia PNH is a complex malformation of cortical development with imaging features distinguishing it from classic bilateral PNH associated with filamin (FLNA) mutations. It distinctively consists of variably sized nodules of neurons along the trigones and temp...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-016-0282-6
更新日期:2016-03-09 00:00:00
abstract:BACKGROUND:CHARGE syndrome is characterized by coloboma, heart defects, choanal atresia, growth retardation, genitourinary malformation and ear abnormalities. The chromodomain helicase DNA-binding protein 7 (CHD7) gene is the major cause of CHARGE syndrome and is inherited in an autosomal dominant manner. Currently, th...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0813-z
更新日期:2019-05-30 00:00:00
abstract:BACKGROUND:Elastogenesis of elastic extracellular matrix (ECM) which was recognized as a major component of blood vessels has been believed for a long time to play only a passive role in the dynamic vascular changes of typical hypertension. Emilin1 gene participated in the transcription of ECM's formation and was recog...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-10-118
更新日期:2009-11-18 00:00:00
abstract:BACKGROUND:DJ-1 forms part of the neuronal cellular defence mechanism against oxidative insults, due to its ability to undergo self-oxidation. Oxidative stress has been implicated in the pathogenesis of central nervous system damage in different neurodegenerative disorders including Alzheimer's disease and Parkinson's ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-10-105
更新日期:2009-10-13 00:00:00
abstract:BACKGROUND:Nakajo-Nishimura syndrome (NNS) is an autosomal recessive heredity disorder, one of a spectrum of autoinflammatory diseases named proteasome-associated autoinflammatory syndrome (PRAAS) caused by mutations of PSMB8 gene. NNS is characterized by pernio-like skin rashes, intermittent fever, and long clubbed fi...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01060-8
更新日期:2020-06-08 00:00:00
abstract:BACKGROUND:Mutations in the FKBP10 gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found FKBP10 mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-12-152
更新日期:2011-11-22 00:00:00
abstract:BACKGROUND:Estrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues. The objective of this study was to analyze the influence of common polymorphisms of the SHBG gene on serum SHBG, bone mineral den...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-9-112
更新日期:2008-12-17 00:00:00
abstract:BACKGROUND:Recent investigations demonstrated many genetic contributions to the development of human age-related hearing impairment (ARHI), however, reports of factors associated with a reduction in the ARHI risk are rare. Folate metabolism is essential for cellular functioning. Despite the extensive investigations reg...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-12-35
更新日期:2011-03-07 00:00:00
abstract:BACKGROUND:Although vitamin D receptor (VDR) polymorphisms have been shown to be associated with abnormal glucose metabolism, the reported polymorphisms are unlikely to have any biological consequences. The VDR gene has two potential translation initiation sites. A T-to-C polymorphism has been noted in the first ATG (f...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-2-2
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Deep vein thrombosis (DVT) is associated with stroke. Here, we hypothesize that genes associated with DVT may also play roles in the development of stroke. METHODS:we firstly conducted large-scale literature based disease-gene relationship data analysis to explore the genes implicated with DVT and stroke. F...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01108-9
更新日期:2020-10-22 00:00:00
abstract:BACKGROUND:Inflammation is a response of body tissues to injury or irritation. Small RNAs, such as miR-146a and miR-499, participate in various processes of tumorigenesis. A recent study indicates that inflammation and abnormal immune responses may promote malignant progression in cancer development, indicating that in...
journal_title:BMC medical genetics
pub_type: 杂志文章,meta分析
doi:10.1186/s12881-014-0092-7
更新日期:2014-08-10 00:00:00
abstract:BACKGROUND:Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common human microdeletion syndrome and is associated with many cognitive, neurological and psychiatric disorders. The majority of individuals have a 3 Mb deletion while others have a nested 1.5 Mb deletion, but rare atypical deletions have also been...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-014-0106-5
更新日期:2014-10-14 00:00:00
abstract:BACKGROUND:Chronic kidney disease progression has been linked to pro-inflammatory cytokines and markers of inflammation. These markers are also elevated in end-stage renal disease (ESRD), which constitutes a serious public health problem. OBJECTIVE:To investigate whether single nucleotide polymorphisms (SNPs) located ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-13-58
更新日期:2012-07-20 00:00:00
abstract:BACKGROUND:Sjogren-Larsson syndrome is a hereditary neurocutaneous syndrome that is non-progressive in nature. Although neuroregression has been reported in seizure-prone preschool children requiring anti-epileptic treatment, teenage-onset dystonia precipitating neurodegeneration without any immediate causal events has...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-018-0663-0
更新日期:2018-08-29 00:00:00
abstract:BACKGROUND:Ocular albinism type 1 (OA1) is an X-linked ocular disorder characterized by a severe reduction in visual acuity, nystagmus, hypopigmentation of the retinal pigmented epithelium, foveal hypoplasia, macromelanosomes in pigmented skin and eye cells, and misrouting of the optical tracts. This disease is primari...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-7-41
更新日期:2006-04-28 00:00:00
abstract:BACKGROUND:Asthma genetics has been extensively studied and many genes have been associated with the development or severity of this disease. In contrast, the genetic basis of allergic rhinitis (AR) has not been evaluated as extensively. It is well known that asthma is closely related with AR since a large proportion o...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-14-51
更新日期:2013-05-10 00:00:00
abstract:BACKGROUND:The Krüppel-like factor (KLF) family consists of transcription factors that can activate or repress different genes implicated in processes such as differentiation, development, and cell cycle progression. Moreover, several of these proteins have been implicated in glucose homeostasis, making them candidate ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-8-53
更新日期:2007-08-09 00:00:00
abstract:BACKGROUND:Vitamin D has been shown to exert manifold immunomodulatory effects. Type 1 diabetes mellitus (T1DM) is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse. We studied the association between T1DM and the initiation codon polymorphism in exon 2 of the vitamin D ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-2-7
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum. Initial studies have implicated rare copy number variations (CNVs), including recurrent duplications of chromosomal region 22q11.21, in BEEC etiology. METHODS:To detect further CNVs,...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-016-0299-x
更新日期:2016-04-30 00:00:00
abstract:BACKGROUND:The results of meta-analyses conducted by previous association studies between total homocysteine and schizophrenia suggest that an elevated total homocysteine level is a risk factor for schizophrenia. However, observational studies have potential limitations, such as confounding and reverse causation. In th...
journal_title:BMC medical genetics
pub_type: 杂志文章,meta分析
doi:10.1186/s12881-015-0197-7
更新日期:2015-07-26 00:00:00