Abstract:
:Clinical exome sequencing (CES) has become an increasingly popular diagnostic tool in patients with heterogeneous genetic disorders, especially in those with neurocognitive phenotypes. Utility of CES in consanguineous populations has not yet been determined on a large scale. A clinical cohort of 149 probands from Qatar with suspected Mendelian, mainly neurocognitive phenotypes, underwent CES from July 2012 to June 2014. Intellectual disability and global developmental delay were the most common clinical presentations but our cohort displayed other phenotypes, such as epilepsy, dysmorphism, microcephaly and other structural brain anomalies and autism. A pathogenic or likely pathogenic mutation, including pathogenic CNVs, was identified in 89 probands for a diagnostic yield of 60%. Consanguinity and positive family history predicted a higher diagnostic yield. In 5% (7/149) of cases, CES implicated novel candidate disease genes (MANF, GJA9, GLG1, COL15A1, SLC35F5, MAGE4, NEUROG1). CES uncovered two coexisting genetic disorders in 4% (6/149) and actionable incidental findings in 2% (3/149) of cases. Average time to diagnosis was reduced from 27 to 5 months. CES, which already has the highest diagnostic yield among all available diagnostic tools in the setting of Mendelian disorders, appears to be particularly helpful diagnostically in the highly consanguineous Middle Eastern population.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Yavarna T,Al-Dewik N,Al-Mureikhi M,Ali R,Al-Mesaifri F,Mahmoud L,Shahbeck N,Lakhani S,AlMulla M,Nawaz Z,Vitazka P,Alkuraya FS,Ben-Omran Tdoi
10.1007/s00439-015-1575-0subject
Has Abstractpub_date
2015-09-01 00:00:00pages
967-80issue
9eissn
0340-6717issn
1432-1203pii
10.1007/s00439-015-1575-0journal_volume
134pub_type
杂志文章相关文献
HUMAN GENETICS文献大全abstract::A hereditary disease with excess mortality such as haemophilia is maintained in the population by the occurrence of new cases, i.e. mutations. In haemophilia, mutations may arise in female or male ancestors of a 'new' patient. The ratio of the mutation frequencies in males over females determines the prior risk of car...
journal_title:Human genetics
pub_type: 杂志文章,meta分析
doi:10.1007/BF00197695
更新日期:1990-12-01 00:00:00
abstract::Vascular twin nevi, i.e., telangiectatic nevus and nevus anemicus occurring together and adjacent to each other, can be explained as twin spots resulting from a somatic recombination. It is so far unclear, however, whether the postulated underlying autosomal recessive mutations are allelic. This problem can be approac...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/BF00202421
更新日期:1991-01-01 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 gene frequency of beta-thalassemia among Filipinos is estimated to be 0.02, although little is known about the mutations involved. Recently, an extensive beta-thalassemia deletion was reported in several unrelated individuals of Filipino descent. The deletion begins approximately 4 kb upstream of the beta-globin g...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00211021
更新日期:1994-11-01 00:00:00
abstract::The human gene locus c-MEL was identified following transfection of genomic DNA from the human melanoma cell line NK14; it has previously been assigned to chromosome 19 (p13.2-q13.2) by analysis of somatic cell hybrids. We have further refined the position of this gene to the proximal region of 19p (cen-p13.2), using ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00283697
更新日期:1989-03-01 00:00:00
abstract::The erythrocytic and liver pyruvate kinases (PK) from a patient with congenital nonspherocytic hemolytic anemia have been studied. In red blood cells, the residual activity, 28% of the normal control, presented normal kinetic properties, instability to heat and urea, and slow electrophoretic mobility. The L-type PK fr...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00296454
更新日期:1982-01-01 00:00:00
abstract::Angelman syndrome is a neuro-developmental disorder caused by genetic abnormalities affecting the maternal gene expression in the chromosome region 15q11-q13. In a study group of 45 Finnish Angelman patients, a recurrence of a del(15)(q11q13) was detected in one family. The mother's chromosomes 15 were structurally no...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000336
更新日期:2000-07-01 00:00:00
abstract::DNA haplotype constellations of the beta-globin gene cluster have been analyzed in German families with hemoglobinopathies (Hb Freiburg, Hb Köln, Hb Presbyterian) and beta-thalassemias. The polymorphic patterns obtained were compared to those found in families from Greece, Italy, and Turkey affected by beta-thalassemi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00284577
更新日期:1985-01-01 00:00:00
abstract::Linkage relationships to unassigned and provisionally assigned genetic markers were examined from 53 families segregating for various fragile sites. Fragile sites were at Xq27, 2q13, 6p23, 9p21, 9p32, 10q23, 10q25, 11q13, 11q23, 12q13 and 16p12. No new assignments were made but extensive exclusion data are presented f...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00285035
更新日期:1983-01-01 00:00:00
abstract::Split hand/foot malformation (SHFM) with long bone deficiency (SHFLD) is a distinct entity in the spectrum of ectrodactylous limb malformations characterised by associated tibial a/hypoplasia. Pedigrees with multiple individuals affected by SHFLD often include non-penetrant intermediate relatives, making genetic mappi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-007-0390-7
更新日期:2007-09-01 00:00:00
abstract::The vasopressin V2 receptor (V2R) and the aquaporin-2 genes of two unrelated male patients with congenital nephrogenic diabetes insipidus were analyzed. The V2R gene of the patient of family 1 had the wild-type sequence. Consequently, the coding region of the aquaporin-2 gene including the exon-intron junctions was se...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050264
更新日期:1996-11-01 00:00:00
abstract::The genetically determined polymorphism of human pancreatic amylase (E.C. 3.2.1.1), AMY2, is demonstrated in serum specimens by agarose gel electrophoresis. We investigated 325 mother-child pairs and 2594 unrelated individuals from southwestern Germany. This study confirms the formal hypothesis of two common alleles A...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00287179
更新日期:1979-10-01 00:00:00
abstract::The pattern of X-chromosome inactivation was analyzed, by means of two different DNA probes (pSPT-PGK and M27 beta), in several cell lineages derived from females belonging to a pedigree with X-linked immunodeficiency with hyper-IgM (HIGM1). Non-random X-chromosome inactivation was demonstrated in T cells, B cells, an...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00206059
更新日期:1991-12-01 00:00:00
abstract::A Drosophila-related expressed sequence tag (DRES) with sequence similarity to the peanut gene has previously been localized to human chromosome 22q11. We have isolated the cDNA corresponding to this DRES and show that it is a novel member of the family of septin genes, which encode proteins with GTPase activity thoug...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050576
更新日期:1997-11-01 00:00:00
abstract::Cowden disease is an autosomal dominant disorder associated with an elevated risk of breast, thyroid and skin cancers, in which germline mutations of a tumour suppressor gene (PTEN) have been identified. PTEN has a dual-specificity tyrosine phosphatase domain thought to be essential for tumour suppression. Previous ge...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000317
更新日期:2000-07-01 00:00:00
abstract::Our understanding of the process of autophagy and its role in health and diseases has grown remarkably in the last two decades. Early work established autophagy as a general bulk recycling process which involves the sequestration and transport of intracellular material to the lysosome for degradation. Currently, autop...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/s00439-019-02031-7
更新日期:2020-03-01 00:00:00
abstract::Congenital atrichia is a rare autosomal recessive disorder of hair development, characterized by complete loss of hair shortly after birth. Evidence of linkage to chromosome 8p12 has been established, implicating the human homolog of the mouse hairless (hr) gene as a candidate gene. We have previously identified misse...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050840
更新日期:1998-10-01 00:00:00
abstract::Mutual correction of co-cultivated fibroblasts from patients with Hunter's and Hurler's syndrome could be inhibited by either fructose 1-phosphate or mannose 6-phosphate. In the presence of fructose 1-phosphate a 50% mixture of fibroblasts from a patient with Hunter's syndrome and a normal homozygous individual showed...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00569706
更新日期:1982-01-01 00:00:00
abstract::In man a common fragile site is known to occur at 3p14. We studied the expression of this fragility in a group of 70 normal healthy subjects. Chromosome breaks, chromatid breaks and gaps at 3p14 could be observed in every examined individual, and in a total of 7000 metaphases they were seen in a mean of 4% of cells. F...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291880
更新日期:1986-03-01 00:00:00
abstract::We have analysed the spread of X inactivation in an individual with an unbalanced 46,X,der(X)t(X;10)(q26.3;q23.3) karyotype. Despite being trisomic for the region 10q23.3-qter, both the proband and her aunt with the same karyotype presented only with secondary amenorrhoea and lacked any features normally associated wi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390100578
更新日期:2001-09-01 00:00:00
abstract::A case of human piebaldism with white forelock is presented, with emphasis on the unusual aspect of expansion and diminution of the hypomelanotic areas. Possible mechanisms of piebaldism and of changes in the hypomelanotic areas are discussed. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00278885
更新日期:1976-10-28 00:00:00
abstract::The objective of this study is to shed light on the phenotype and inheritance pattern of rare 13q33-q34 microdeletions. Appropriate cases were retrieved using local databases of two largest Israeli centers performing CMA analysis. In addition, literature search in PubMed, DECIPHER and ClinVar databases was performed. ...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/s00439-019-02048-y
更新日期:2019-10-01 00:00:00
abstract::Sphingolipid activator protein (SAP) deficiency, previously described in two sibs and shown to be caused by the absence of the common saposin precursor (prosaposin), was further characterized by biochemical lipid and enzyme studies and by ultrastructural analysis. The 20-week-old fetal sib had increased concentrations...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00219682
更新日期:1993-09-01 00:00:00
abstract::To dissect the genetic architecture of sexual dimorphism in obesity-related traits, we evaluated the sex-genotype interaction, sex-specific heritability and genome-wide linkages for seven measurements related to obesity. A total of 1,365 non-diabetic Chinese subjects from the family study of the Stanford Asia-Pacific ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-010-0877-5
更新日期:2010-11-01 00:00:00
abstract::Alpha thalassemia retardation associated with chromosome16 (ATR-16 syndrome) is defined as a contiguous gene syndrome resulting from haploinsufficiency of the alpha-globin gene cluster and genes involved in mental retardation (MR). To date, only few cases have been described which result from pure monosomy for a delet...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-007-0399-y
更新日期:2007-11-01 00:00:00
abstract::Rapid progress in the sequencing of the genome of man and other species allows for the comparative analysis of their genetic structure and content. We have used a combined biochemical and computer-based approach to characterize a 146 kb human genomic bacterial artificial chromosome clone from chromosome 5q13 and disco...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-001-0610-5
更新日期:2001-11-01 00:00:00
abstract::To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 yea...
journal_title:Human genetics
pub_type: 杂志文章,meta分析
doi:10.1007/s00439-014-1500-y
更新日期:2015-02-01 00:00:00
abstract::We describe a genetic polymorphism of cytosol polypeptide with mol. wt. of 38,000 detected in phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes by two-dimensional gel electrophoresis. Three different electrophoretic phenotypes (type 1-1, 2-1, 2-2) of the polypeptide have been identified in a Japanese po...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00295371
更新日期:1985-01-01 00:00:00
abstract::This study was undertaken to analyze DNA methylation profiling at the monoamine oxidase A (MAOA) locus, in order to determine whether abnormal DNA methylation is involved in the development of schizophrenia. We recruited a total of 371 patients with paranoid schizophrenia (199 males and 172 females) and 288 unrelated ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-011-1131-5
更新日期:2012-07-01 00:00:00
abstract::We previously identified a low-frequency (1.1 %) coding variant (G45R; rs200573126) in the adiponectin gene (ADIPOQ) which was the basis for a multipoint microsatellite linkage signal (LOD = 8.2) for plasma adiponectin levels in Hispanic families. We have empirically evaluated the ability of data from targeted common ...
journal_title:Human genetics
pub_type: 临床试验,杂志文章
doi:10.1007/s00439-014-1511-8
更新日期:2015-02-01 00:00:00