Abstract:
BACKGROUND:Congenital cataract is the leading cause of blindness in children worldwide. Approximately half of all congenital cataracts have a genetic basis. Protein aggregation is the single most important factor in cataract formation. METHODS:A four-generation Chinese family diagnosed with autosomal dominant congenital cataracts and microphthalmia was recruited at the Shengjing Hospital of China Medical University. Genomic DNA was extracted from the peripheral blood of the participants. All coding exons and flanking regions of seven candidate genes (CRYAA, CRYBA4, CRYBB2, CRYGC, GJA8, MAF, and PITX3) were amplified and sequenced. Restriction fragment length polymorphism (RFLP) assays were performed to confirm the candidate causative variant, c.35G > T in the CRYAA gene. We constructed pcDNA3.1(+)-CRYAA expression plasmids containing either the wild-type or the R12L mutant alleles and respectively transfected them into HEK293T cells and into HeLa cells. Western blotting was performed to determine protein expression levels and protein solubility. Immunofluorescence was performed to determine protein sub-cellular localization. RESULTS:A heterozygous variant c.35G > T was identified in exon 1 of CRYAA, which resulted in a substitution of arginine to leucine at codon 12 (p.R12L). The nucleotide substitution c.35G > T was co-segregated with the disease phenotype in the family. The mutant R12L-CRYAA in HEK293T cells showed a significant increase in the expression level of the CRYAA protein compared with the wild-type cells. Moreover, a large amount of the mutant protein aggregated in the precipitate where the wild-type protein was not detected. Immunofluorescence studies showed that the overexpressed mutant CRYAA in HeLa cells formed large cytoplasmic aggregates and aggresomes. CONCLUSIONS:In summary, we described a case of human congenital cataract and microphthalmia caused by a novel mutation in the CRYAA gene, which substituted an arginine at position 12 in the N-terminal region of αA-crystallin. The molecular mechanisms that underlie the pathogenesis of human congenital cataract may be characterized by the prominent effects of the p.R12L mutation on αA-crystallin aggregation and solubility. Our study also expands the spectrum of known CRYAA mutations.
journal_name
BMC Med Genetjournal_title
BMC medical geneticsauthors
Song Z,Si N,Xiao Wdoi
10.1186/s12881-018-0695-5subject
Has Abstractpub_date
2018-10-19 00:00:00pages
190issue
1issn
1471-2350pii
10.1186/s12881-018-0695-5journal_volume
19pub_type
杂志文章abstract:BACKGROUND:Mitotic recombination is important for inactivating tumour suppressor genes by copy-neutral loss of heterozygosity (LOH). Although meiotic recombination maps are plentiful, little is known about mitotic recombination. The APC gene (chr5q21) is mutated in most colorectal tumours and its usual mode of LOH is m...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-10-54
更新日期:2009-06-10 00:00:00
abstract:BACKGROUND:Southern China provinces have high incidence of thalassemia, however, sporadic cases can be found in northern China as well. METHODS:People resided in north China who were suspected to have thalassemia were detected mutations by gap-polymerase chain reaction (Gap-PCR) and reverse dot blot (RDB) analyses. Th...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0818-7
更新日期:2019-05-22 00:00:00
abstract:BACKGROUND:Sequence variants in genes functioning in folate-mediated one-carbon metabolism are hypothesized to lead to changes in levels of homocysteine and DNA methylation, which, in turn, are associated with risk of cardiovascular disease. METHODS:330 SNPs in 52 genes were studied in relation to plasma homocysteine ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-12-150
更新日期:2011-11-21 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:Epigenetics could facilitate greater understanding of disparities in the emergence of childhood obesity. While blood is a common tissue used in human epigenetic studies, saliva is a promising tissue. Our prior findings in non-obese preschool-aged Hispanic children identified 17 CpG dinucleotides for which di...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-0968-7
更新日期:2020-02-14 00:00:00
abstract:BACKGROUND:In X-linked dilated cardiomyopathy due to dystrophin mutations which abolish the expression of the M isoform (5'-XLDC), the skeletal muscle is spared through the up-regulation of the Brain (B) isoform, a compensatory mechanism that does not appear to occur in the heart of affected individuals. METHODS:We qu...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-13-20
更新日期:2012-03-28 00:00:00
abstract:BACKGROUND:The increasing number of available genotypes for genetic studies in humans requires more advanced techniques of analysis. We previously reported significant univariate associations between gene polymorphisms and antidepressant response in mood disorders. However the combined analysis of multiple gene polymor...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-5-27
更新日期:2004-12-09 00:00:00
abstract:BACKGROUND:Autoimmune diseases with elevated circulating autoantibodies drive tissue damage and the onset of disease. The Fcγ receptors bind IgG subtypes modulating the clearance of circulating immune complexes (CIC). The inner ear damage in Ménière's disease (MD) could be mediated by an immune response driven by CIC. ...
journal_title:BMC medical genetics
pub_type: 杂志文章,多中心研究
doi:10.1186/1471-2350-12-2
更新日期:2011-01-05 00:00:00
abstract:BACKGROUND:Graves disease (GD) is an organ-specific autoimmune disease characterized by hyperthyroidism, diffuse goiter, autoantibodies against thyroid-specific antigens, and dermopathy. Studies of GD have demonstrated the importance of the Th2 and Th17 immune responses in mediating disease progression. In the present ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-13-116
更新日期:2012-11-30 00:00:00
abstract:BACKGROUND:I/D polymorphisms of ACE are associated with the plasma ACE concentration. The ACE is associated with the angiogenesis of ovarian endothelium in vitro as well as steroidogenesis and follicular growth in cattle. Since ACE induces a high blood supply and hypersteroidogenesis in the ovary, it may be associated ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-10-64
更新日期:2009-07-14 00:00:00
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 ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-018-0585-x
更新日期:2018-05-08 00:00:00
abstract:BACKGROUND:Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is increasingly recognized as an inherited arterial disease leading to a step-wise decline and eventually to dementia. CADASIL is caused by mutations in NOTCH3 epidermal growth factor-like repeat that maps to...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-8-67
更新日期:2007-11-09 00:00:00
abstract:BACKGROUND:Polydactyly is one of the most common congenital hand/foot malformations in humans. Mutations in GLI3 have been reported to cause syndromic and non-syndromic forms of preaxial and postaxial polydactylies. CASE PRESENTATION:The patient was a 2-year-old boy who underwent surgery in our hospital. The right han...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0889-5
更新日期:2019-11-09 00:00:00
abstract:BACKGROUND:Ornithine transcarbamylase deficiency (OTCD) is an X-linked recessive disorder involving a defect in the urea cycle caused by OTC gene mutations. Although a total of 417 disease-causing mutations in OTC have been reported, structural abnormalities in this gene are rare. We here describe a female OTCD case ca...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-018-0733-3
更新日期:2018-12-12 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
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journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-018-0622-9
更新日期:2018-07-05 00:00:00
abstract:BACKGROUND:Glucocorticoids have an important role in early growth and development. Glucocorticoid receptor gene polymorphisms have been identified that contribute to the variability in glucocorticoid sensitivity. We examined whether these glucocorticoid receptor gene polymorphisms are associated with growth in fetal an...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-11-39
更新日期:2010-03-03 00:00:00
abstract:BACKGROUND:Rubinstein-Taybi syndrome (RSTS; OMIM #180849, #613684) is a rare autosomal dominant genetic condition characterized by broad thumbs and halluces, facial dysmorphism, short stature and variable degree of intellectual disability. RSTS is associated with mutations in CREBBP and EP300 genes in 50-60% and 5-8% o...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-016-0361-8
更新日期:2016-12-13 00:00:00
abstract:BACKGROUND:Ring chromosomes are one category of structurally abnormal chromosomes that can lead to severe growth retardation and other clinical defects. Traditionally, their diagnosis and characterization has largely relied on conventional cytogenetics and fluorescence in situ hybridization, array-based comparative gen...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-015-0206-x
更新日期:2015-07-30 00:00:00
abstract:BACKGROUND:Many hearing-loss diseases are demonstrated to have Mendelian inheritance caused by mutations in single gene. However, many deaf individuals have diseases that remain genetically unexplained. Auditory neuropathy is a sensorineural deafness in which sounds are able to be transferred into the inner ear normall...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-017-0400-0
更新日期:2017-03-23 00:00:00
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journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-14-77
更新日期:2013-07-26 00:00:00
abstract:BACKGROUND:Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract with an increased risk of colorectal cancer. Germline mutations in two genes, SMAD4 and BMPR1A, have been identified to cause ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01135-6
更新日期:2020-10-08 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:We report a large family with four successive generations, presenting with a complex phenotype of severe congenital neutropenia (SCN), partially penetrant monocytosis, and hearing loss of varying severity. METHODS:We performed whole exome sequencing to identify the causative variants. Sanger sequencing was ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-0971-z
更新日期:2020-02-17 00:00:00
abstract:BACKGROUND:Cohen syndrome (CS) is an uncommon developmental disease with evident clinical heterogeneity. VPS13B is the only gene responsible for CS. Only few sporadic cases of CS have been reported in China. CASE PRESENTATION:A Chinese family with two offspring-patients affected by developmental delay and intellectual...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0920-x
更新日期:2019-11-21 00:00:00
abstract:BACKGROUND:The TWNK gene encodes the twinkle protein, which is a mitochondrial helicase for DNA replication. The dominant TWNK variants cause progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, while the recessive variants cause mitochondrial DNA depletion syndrome 7 and Perraul...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-020-01002-4
更新日期:2020-03-31 00:00:00
abstract:BACKGROUND:Hereditary non-syndromic hearing loss is the most common inherited sensory defect in humans. The KCNQ4 channel belongs to a family of potassium ion channels that play crucial roles in physiology and disease. Mutations in KCNQ4 underlie deafness non-syndromic autosomal dominant 2, a subtype of autosomal domin...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-017-0396-5
更新日期:2017-03-24 00:00:00
abstract:BACKGROUND:Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease with a high risk for colorectal and endometrial cancer caused by germline mutations in DNA mismatch-repair genes (MMR). HNPCC accounts for approximately 2 to 5% of all colorectal cancers. Here we present 6 novel mutations in ...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-5-16
更新日期:2004-06-24 00:00:00
abstract:BACKGROUND:The present study is an analysis of the frequencies of HLA-A and -B antigens and HLA haplotypes in two groups of individuals homozygous for the two main HFE mutations (C282Y and H63D) and a group heterozygous for the S65C mutation. METHODS:The study population includes: 1123 healthy individuals, 100 homozyg...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/1471-2350-5-25
更新日期:2004-10-21 00:00:00
abstract:BACKGROUND:Tumor necrosis factor superfamily member 15 (TNFSF15) is closely related to tumorigenesis and development. This study aimed to investigate the correlations between TNFSF15 polymorphisms and genetic susceptibility to lung cancer. METHODS:This case-control study included 209 small cell lung cancer patients (S...
journal_title:BMC medical genetics
pub_type: 杂志文章
doi:10.1186/s12881-019-0762-6
更新日期:2019-02-08 00:00:00