Abstract:
:L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive neurometabolic disorder characterized essentially by the presence of elevated levels of L-2-hydroxyglutaric acid (LGA) in plasma, cerebrospinal fluid and urine. L2HGA is caused by a deficiency in the L2-Hydroxyglutaric dehydrogenase (L2HGDH) enzyme involved in the oxidation of LGA to the alpha 2-ketoglutarate. LGA has been proposed as an endo- and exogenous cytotoxic organic acid that induces free radical formation and generation of reactive oxygen species (ROS). In this report, we analyzed 14 L2HGA patients belonging to six unrelated consanguineous families the south of Tunisia. The patients were diagnosed with L2HGA disease confirmed on the presence of high level of LGA in urine. We analyzed the L2HGDH gene in all probands and identified the same c.241A>G homozygous mutation, which was previously reported in Tunisia. We also used intragenic single nucleotide length polymorphisms (SNPs) and two extragenic microsatellites flanking the L2HGDH gene to confirm the founder effect of c.241A>G mutation in the 14 studied cases. In addition, we carried out the measurement of the oxidative stress parameters in the plasma of L2HGA patients which revealed a significant increase in the malondialdehyde levels (MDA), a biomarker of lipid peroxydation, and the reduced glutathione (GSH). A diminution of the antioxidant enzyme activities including superoxide dismutase (SOD), glutathione peroxidase (GPx), was also observed.
journal_name
J Hum Genetjournal_title
Journal of human geneticsauthors
Jellouli NK,Hadj Salem I,Ellouz E,Kamoun Z,kamoun F,tlili A,Kaabachi N,Triki C,Fakhfakh F,Tunisian Network on Mental Retardation study.doi
10.1038/jhg.2014.4subject
Has Abstractpub_date
2014-04-01 00:00:00pages
216-22issue
4eissn
1434-5161issn
1435-232Xpii
jhg20144journal_volume
59pub_type
杂志文章abstract::The name Fon-Jou Hsieh was inadvertently omitted from the list of authors. The name should be added as the third author of the article. ...
journal_title:Journal of human genetics
pub_type: 杂志文章,已发布勘误
doi:10.1007/s10038-006-0367-8
更新日期:2006-03-01 00:00:00
abstract::Mutations in BRCA genes elevate risk for breast and ovarian cancer. These mutations are population specific. As there are no data on BRCA mutation screening on larger number of probands in Serbia to date, aim of this study was to determine types and frequencies of BRCA mutations in individuals from high-risk families ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2013.30
更新日期:2013-08-01 00:00:00
abstract::Natural tooth loss represents a major medical issue within the elderly population, since it impairs masticatory function critical for oral intake of essential nutrition. Contribution of genetic factors has been implicated in the determination of natural tooth loss; degree of reduction in number of natural teeth remain...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-003-0024-4
更新日期:2003-01-01 00:00:00
abstract::Cumulative data obtained from two relatively large pedigrees of a unique reciprocal chromosomal translocation (RCT) t(1;11)(p36.22;q12.2) ascertained by three miscarriages (pedigree 1) and the birth of newborn with hydrocephalus and myelomeningocele (pedigree 2) were used to estimate recurrence risks for different pre...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2014.92
更新日期:2014-12-01 00:00:00
abstract::Ectodermal-dysplasia-syndactyly syndrome (EDSS1) is a rare form of ectodermal dysplasia (ED), affecting skin and its appendages mainly hair, teeth and nails. In the present study, we have investigated a large consanguineous Pakistani family with 10 individuals showing features of EDSS1. Human genome was screened using...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2011.18
更新日期:2011-05-01 00:00:00
abstract::Mucopolysaccharidosis IVA (MPS IVA) is a degenerative systemic skeletal dysplasia, in which children exhibit marked short stature and become physically handicapped. This study evaluated the growth patterns of patients treated with enzyme replacement therapy (ERT), compared with those of untreated patients. Cross-secti...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-019-0604-6
更新日期:2019-07-01 00:00:00
abstract::Tandem mass screening has recently been started in Japan, but genetic screening has yet to be widely performed in neonates and many unexpected deaths are still being reported. We previously reported two cases of sudden infant death that may have been prevented had newborn screening been performed. In this study, we re...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2017.79
更新日期:2017-11-01 00:00:00
abstract::Hypercholesterolemia is caused by different interactions of lifestyle and genetic determinants. At the genetic level, it can be attributed to the interactions of multiple polymorphisms, or as in the example of familial hypercholesterolemia (FH), it can be the result of a single mutation. A large number of genetic mark...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2012.34
更新日期:2012-06-01 00:00:00
abstract::Human minisatellite B6.7 shows extensive allele length and structural variability in north Europeans. We analysed this locus in the Japanese population. Allele size distributions showed that Japanese retain extensive allele length variability but have significantly smaller alleles compared with north Europeans. In con...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380200031
更新日期:2002-01-01 00:00:00
abstract::Osteosclerotic metaphyseal dysplasia (OSMD) is a rare skeletal dysplasia characterized by osteosclerotic metaphyses with osteopenic diaphyses of the long tubular bones. Our previous study identified a homozygous elongation mutation in leucine-rich repeat kinase 1 gene (LRRK1) in a patient with OSMD and showed that Lrr...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2016.136
更新日期:2017-03-01 00:00:00
abstract::Factors predisposing to the phenotypic features of familial combined hyperlipidemia have not been clearly defined. In the course of investigating familial coronary artery disease in Utah, we identified a three-generation family in which multiple members were affected with type IIa hyperlipoproteinemia (HLP IIa), type ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050202
更新日期:2000-01-01 00:00:00
abstract::DNase II is an important enzyme for DNA fragmentation and degradation during programmed cell death and, consequently, a potential candidate gene for genetic study of systemic lupus erythematosus (SLE). Genetic associations of DNase II with SLE and related phenotypes were examined in Korean patients with SLE. A total o...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-004-0227-3
更新日期:2005-01-01 00:00:00
abstract::Variation in the human monoamine oxidase A (MAO-A) gene can influence neurotransmittor levels and is thought to have a role in many behavioral traits. The genetic architecture of MAO-A is known to vary across different geographic subgroups. Previous studies have reported evidence for positive selection within the MAO-...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2012.19
更新日期:2012-05-01 00:00:00
abstract::Estrogen was considered to be an important protective factor for cardiovascular diseases in women. Genetic association studies suggested that variations of ESR1and ESR2 genes might have a potential role in lipid profile. Our study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) of ESR1 a...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2009.122
更新日期:2010-01-01 00:00:00
abstract::The roles of the erythropoietin (Epo) 3' enhancer in the activation of gene expression in response to hypoxia were investigated. The enhancer contains hypoxia-inducible enhancer binding site 1 (HIF-1 element) and two direct repeats of hexanucleotide consensus nuclear receptor half site (HNF-4 element). HIF-1, which is...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050163
更新日期:1999-01-01 00:00:00
abstract::Interleukin (IL11) is a member of the interleukin 6 (IL6)-related cytokine subfamily, which stimulates T cell-dependent development of immunoglobulin-producing B cells. IL11 is also an important paracrine regulator of bone metabolism that induces formation of osteoclasts. In the work reported here, we sequenced the en...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380170052
更新日期:2001-01-01 00:00:00
abstract::We used magnetic resonance imaging (MRI) to examine the brain of a typical Coffin-Lowry syndrome (CLS) patient. There were many small perivascular focal areas of hypointensity in the white matter on T1-weighted images, similar to those found in mucopolysaccharidosis or perivascular leukomalacia. However, these changes...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050038
更新日期:1998-01-01 00:00:00
abstract::Dent's disease (DD) involves nephrocalcinosis, urolithiasis, hypercalciuria, LMW proteinuria, and renal failure in various combinations. Males are affected. It is caused by mutations in the chloride channel CLCN5 gene. It has been suggested that DD is underdiagnosed, occurring in less overt forms, apparently without f...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-005-0317-x
更新日期:2006-01-01 00:00:00
abstract::Since adducin modulates cellular sodium retention, its follows that ADD1, which encodes the alpha-subunit of adducin, is an attractive candidate gene for blood pressure variation. Association studies examining the relationship between polymorphism at ADD1 codon 460 (G460W) and both hypertension and blood pressure, whi...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050148
更新日期:1999-01-01 00:00:00
abstract::The identification of anticipation in schizophrenia is a recent focus in the genetic epidemiology of schizophrenia, although it involves some controversial methodological issues. We explored the evidence of anticipation among 44 Japanese two-generation pairs with schizophrenia found by reviewing nine years of admissio...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s100380050076
更新日期:1998-01-01 00:00:00
abstract::Androgen insensitivy syndrome (AIS) is the most frequent cause of male pseudohermaphroditism resulting from target-organ resistance to androgen action. Individuals bearing the complete form of the disease (CAIS) present a female phenotype and a lack of pubic and axillary hair. In the present study, four 46,XY patients...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-003-0036-0
更新日期:2003-01-01 00:00:00
abstract::Methylation-specific (MS) multiplex ligation-dependent probe amplification (MLPA) at two differentially methylated regions (DMRs) at chromosome 11p15, H19-DMR and LIT1-DMR, and microsatellite analysis for uniparental disomy (UPD) at chromosome 7 or 11, have been recommended for the genetic diagnosis of the Beckwith-Wi...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2013.67
更新日期:2013-09-01 00:00:00
abstract::Carnitine-acylcarnitine translocase (CACT) and carnitine palmitoyltransferase II (CPT2) are key enzymes for transporting long-chain fatty acids into mitochondria. Deficiencies of these enzymes, which are clinically characterized by life-threatening non-ketotic hypoglycemia and rhabdomyolysis, cannot be distinguished b...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2013.103
更新日期:2013-12-01 00:00:00
abstract::Intellectual disability (ID) accounts for 1% of the general population, and it is caused by the interplay between the genetic and/or environmental factors. The genetic components responsible for the development of ID are highly heterogeneous, and the phenotype and severity of the disease vary in patients even if they ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-020-0809-8
更新日期:2020-10-09 00:00:00
abstract::Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, also known as PC-1) inhibits insulin signal transduction pathway(s). Previous studies have demonstrated the K121Q variant of the ENPP1 gene to have a significant functional role in determining susceptibility to insulin resistance and type 2 diabetes (T2D). To...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-006-0399-0
更新日期:2006-01-01 00:00:00
abstract::Spinocerebellar ataxias (SCAs) are a heterogeneous group of disorders with almost 30 subtypes. The prevalence and relative frequency of each subtype vary among different populations. In this article, we report the relative frequency of six SCA subtypes in the Thai population and attempt to explain the observed pattern...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/jhg.2009.27
更新日期:2009-05-01 00:00:00
abstract::Recently, haplotype-based association studies have become popular for detecting disease-related or drug-response-associated genes. In these studies, it has been gradually recognized that a haplotype block structure is important. A rational and automatic method for identifying the haplotype block structure from SNP dat...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1007/s10038-007-0176-8
更新日期:2007-01-01 00:00:00
abstract::MEIS2 aberrations are considered to be the cause of intellectual disability, cleft palate and cardiac septal defect, as MEIS2 copy number variation is often observed with these phenotypes. To our knowledge, only one nucleotide-level change-specifically, an in-frame MEIS2 deletion-has so far been reported. Here, we rep...
journal_title:Journal of human genetics
pub_type: 杂志文章,评审
doi:10.1038/jhg.2016.54
更新日期:2016-09-01 00:00:00
abstract::TDP2 encodes a 5'-tyrosyl DNA phosphodiesterase required for the efficient repair of double-strand breaks (DSBs) induced by the abortive activity of DNA topoisomerase II (TOP2). To date, only three homozygous variants in TDP2 have been reported in six patients from four unrelated pedigrees with spinocerebellar ataxia ...
journal_title:Journal of human genetics
pub_type: 杂志文章
doi:10.1038/s10038-020-0800-4
更新日期:2020-12-01 00:00:00
abstract::Essential hypersomnia (EHS) is a lifelong disorder characterized by excessive daytime sleepiness without cataplexy. EHS is associated with human leukocyte antigen (HLA)-DQB1*06:02, similar to narcolepsy with cataplexy (narcolepsy). Previous studies suggest that DQB1*06:02-positive and -negative EHS are different in te...
journal_title:Journal of human genetics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/s10038-018-0518-8
更新日期:2018-12-01 00:00:00