Abstract:
:Several single-gene disorders with clinical and radiological characteristics similar to those observed in multiple sclerosis (MS) patients have been described. To evaluate whether this phenotypic overlap can be ascribed to a common genetic etiology, 28 genes known to present pathogenic mutations for 24 of these disorders were sequenced in 270 MS patients. All identified variants were genotyped in 2131 MS cases and 830 healthy controls, and those exclusively observed in patients were assessed for segregation within families. This analysis identified 9 rare variants in 6 genes segregating with disease in 13 families. Four different mutations were identified in CYP27A1, including a reported pathogenic mutation for cerebrotendinous xanthomatosis (p.R405W), which was observed in six patients from a multi-incident family, three diagnosed with MS, two with an undefined neurological disease and one seemingly healthy. A LYST p.V1678A and a PDHA1 p.K387Q mutation were both observed in five MS patients from three separate multi-incident families. In addition, CLCN2 p.V174G, GALC p.D162E and POLG p.R361G were each identified in two MS patients from one family. This study suggests a shared genetic etiology between MS and the characterized single-gene disorders, and highlights cholesterol metabolism and the synthesis of oxysterols as important biological mechanisms for familial MS.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Traboulsee AL,Sadovnick AD,Encarnacion M,Bernales CQ,Yee IM,Criscuoli MG,Vilariño-Güell Cdoi
10.1007/s00439-017-1784-9subject
Has Abstractpub_date
2017-06-01 00:00:00pages
705-714issue
6eissn
0340-6717issn
1432-1203pii
10.1007/s00439-017-1784-9journal_volume
136pub_type
杂志文章相关文献
HUMAN GENETICS文献大全abstract::Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene wit...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-010-0790-y
更新日期:2010-03-01 00:00:00
abstract::We have used the polymerase chain reaction to amplify two variable number of tandem repeats (VNTRs) within a region of repetitive DNA located in intron 40 of the von Willebrand factor (vWf) gene. Heterozygosity for VNTR I was observed in 30 out of 39 normal unrelated individuals tested (77%), and for VNTR II in 29 out...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00217122
更新日期:1992-05-01 00:00:00
abstract::A new case of "free" trisomy for the short arm of No. 9 chromosome identified by Giemsa staining and "Giemsa-11 technique" is reported. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00284440
更新日期:1976-09-10 00:00:00
abstract::Otosclerosis is a common form of hearing loss which typically presents in young adults. The disease has a familial, monogenic form and a non-familial form with a more complex aetiology. A previous genome wide association study identified evidence that variants within RELN are associated with the condition. Other genes...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-018-1889-9
更新日期:2018-05-01 00:00:00
abstract::Male identical twins with r(18)/normal mosaicism are reported. Twin 1 has the characteristic manifestations of the r(18) syndrome, but twin 2 shows a normal phenotype. Cytogenetic study of cultured lymphocytes revealed that the proportions of r(18) are 19.7% and 19.2%, respectively. However in the fibroblast cultures,...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00304559
更新日期:1982-01-01 00:00:00
abstract::In this paper observations are summarized and speculations discussed, and it is suggested that some loci on the distal short arm of the X chromosome (Xp) are not randomly inactivated in the female, because they are within the proximal part of the pairing segment between Xp and Yp. This peculiarity of gene expression m...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00303003
更新日期:1982-01-01 00:00:00
abstract::X chromosome inactivation results in dosage equivalency for X-linked gene expression between males and females. However, some X-linked genes show variable X inactivation, being expressed from the inactive X in some females but subject to inactivation in other women. The human tissue inhibitor of metalloproteinases-1 (...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-002-0676-8
更新日期:2002-03-01 00:00:00
abstract::Given that a large number of candidate genes coding for a tendency toward obesity have been identified and some findings have been replicated, we explored characteristics of those who would be most likely to obtain future genetic testing for this tendency. During a series of focus groups, obese respondents rated their...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-006-0252-8
更新日期:2007-01-01 00:00:00
abstract::Sarcoidosis is known to be a systemic granulomatous disorder characterized by a cell-mediated Th1-type inflammatory response. To identify a key genetic factor in the pathogenesis of sarcoidosis, we investigated single nucleotide polymorphisms within 10 candidate genes involved in type 1 immune process ( IFNA17, IFNB, ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-004-1099-5
更新日期:2004-04-01 00:00:00
abstract::Dense sets of hundreds of thousands of markers have been developed for genome-wide association studies. These marker sets are also beneficial for linkage analysis of large, deep pedigrees containing distantly related cases. It is impossible to analyse jointly all genotypes in large pedigrees using the Lander-Green Alg...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-007-0323-5
更新日期:2007-05-01 00:00:00
abstract::The lines of Blaschko represent a nonrandom developmental pattern of the skin fundamentally differing from the system of dermatomes. Many nevoid skin lesions display an arrangement following these lines. This is a review of case reports providing photographically documented evidence that the lines of Blaschko become m...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/BF00273442
更新日期:1985-01-01 00:00:00
abstract::A severe form of autosomal recessive retinitis pigmentosa (arRP) was identified in a large Pakistani family ascertained in the Punjab province of Pakistan. All affected individuals in the family had night blindness in early childhood, early complete loss of useful vision, and typical RP fundus changes plus macular deg...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-005-0054-4
更新日期:2005-12-01 00:00:00
abstract::To elucidate genetic abnormalities in type I CD36 deficiency, we analyzed 28 Japanese subjects whose platelets and monocytes/macrophages lacked CD36 on their surface. We identified two novel mutations in the CD36 gene. One was a complex deletion/insertion mutation, in which 3 bp, GAG, were deleted at nucleotide (nt) 8...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390100525
更新日期:2001-06-01 00:00:00
abstract::We have recently obtained evidence that the locus corresponding to three groups of partial tracheobronchial cDNAs (A = Jer47, B = Jer57, C = Jer58) which mapped to chromosome 11p15 and was given the symbol MUC5 corresponds to two distinct genes which we have provisionally called MUC5B and MUC5AC. Here we describe the ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00210427
更新日期:1995-09-01 00:00:00
abstract::Stargardt disease (STGD) is one of the most frequent causes of macular degeneration in childhood. Linkage analysis in families with recessive STGD has recently shown genetic homogeneity and a location of the underlying gene at 1p22-p21 in a 4-cM interval. Haplotype analysis in seven Dutch STGD families with 11 highly ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050247
更新日期:1996-10-01 00:00:00
abstract::The precise control of gene expression programs is crucial for the establishment of the diverse gene activity patterns required for the correct development, patterning and differentiation of the myriad of cell types within an organism. The crucial importance of non-coding regions of the genome in the control of gene r...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/s00439-014-1424-6
更新日期:2014-07-01 00:00:00
abstract::Oxidative damage caused by reactive oxygen species (ROS) and other free radicals is involved in a number of pathological conditions including cancer. In a population-based case-control study of non-Hodgkin lymphoma (NHL) (n = 518 cases, 597 controls) among women in Connecticut, we analyzed one or more single nucleotid...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-006-0288-9
更新日期:2007-04-01 00:00:00
abstract::Only two genome-wide association (GWA) screens have been published for melanoma (Nat Genet 47:920-925, 2009; Nat Genet 40:838-840, 2008). Using a unique approach, we performed a genome-wide association study in 156 related melanoma cases from 34 high-risk Utah pedigrees. Genome-wide association analysis was performed ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-011-1048-z
更新日期:2012-01-01 00:00:00
abstract::Highly atopic individuals, with marked allergy, have extremely elevated total plasma IgE levels. To determine if atopy could be associated with structural alterations involving the IGHE gene of the immunoglobulin heavy chain constant region, the genomic DNA from five atopic individuals was examined. We describe here t...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00193590
更新日期:1990-10-01 00:00:00
abstract::We conducted an association study to identify risk variants for familial prostate cancer within the HPCX locus at Xq27 among Americans of Northern European descent. We investigated a total of 507 familial prostate cancer probands and 507 age-matched controls without a personal or family history of prostate cancer. The...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-008-0486-8
更新日期:2008-05-01 00:00:00
abstract::Among 639 spontaneous abortions between the 8th and 14th week of gestation 342 (53.5%) revealed an abnormal karyotype. While the rate of trisomies distinctly increased with advancing maternal age, a decrease in the rate of 45,X conceptuses and polyploidies was observed among abortions from older women. The overall rel...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00205080
更新日期:1993-07-01 00:00:00
abstract::A cytogenetic follow-up has been made of nine mixoploid children found among 11 148 consecutive newborn children. The frequency of the cell line with normal chromosomes increased in all but two, and the increase was statistically significant, being from 20% to 39% in four cases, and from 1% to 17% in three, while in o...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00290218
更新日期:1980-01-01 00:00:00
abstract::Albumin is a developmentally regulated serum protein synthesized in the liver mainly during adulthood. Family studies using variant forms of albumin established autosomal linkage between albumin and group-specific component protein (GS). Since GC has been assigned to human chromosome 4, albumin can be indirectly assig...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00304551
更新日期:1982-01-01 00:00:00
abstract::cDNA probe of the casein kinase 2 alpha subunit gene detects a biallelic PstI polymorphism. This restriction fragment length polymorphism is the first known genetic marker of this gene. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00201680
更新日期:1994-04-01 00:00:00
abstract::Restriction endonucleases have been recently proved to be active on fixed chromosomes, thus they are useful in chromatin structure studies. Within this class of enzymes, Alu I is able to detect the presence and localization of highly repetitive DNA sequences in human and in other mammalian and dipteran species. In thi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291894
更新日期:1986-03-01 00:00:00
abstract::PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. Mutations occur in either heritable or sporadic fashion. Sequencing of cDNA from patients and normal individuals often reveals splicing variants (SVs) of PTEN, some of which are non-mutation related. To investigate whether these SVs we...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-010-0886-4
更新日期:2010-12-01 00:00:00
abstract::The genetic heterogeneity of severe von Willebrand disease (vWd) type III was estimated by analysing extended haplotypes of eleven intragenic restriction fragment length polymorphisms and one variable number of tandem repeat polymorphism in 32 patients from 28 families from Germany or of German origin. All patients we...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00206958
更新日期:1994-12-01 00:00:00
abstract::While recent studies have revealed a substantial portion of the genes underlying human hearing loss, the extensive genetic landscape has not been completely explored. Here, we report a loss-of-function variant (c.72delA) in MPZL2 in three unrelated multiplex families from Turkey and Iran with autosomal recessive nonsy...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-018-1901-4
更新日期:2018-07-01 00:00:00
abstract::Five live-born infants with Patau syndrome were studied for the nondisjunctional origin of the extra chromosome. Transmission modes of chromosomes 13 from parents to a child were determined using both QFQ- and RFA-heteromorphisms as markers, and the origin was ascertained in all of the patients. The extra chromosome h...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00418400
更新日期:1984-01-01 00:00:00
abstract::This paper presents the clinical and cytogenetic findings in a female patient with secondary amenorrhea and normal phenotype. Some difficulties related to karyotype-phenotype correlation are discussed. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00273289
更新日期:1979-04-17 00:00:00