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Analysis of 9p24 and 11p12-13 regions in autism spectrum disorders: rs1340513 in the JMJD2C gene is associated with ASDs in Finnish sample.

https://arctichealth.org/en/permalink/ahliterature144059
Source
Psychiatr Genet. 2010 Jun;20(3):102-8
Publication Type
Article
Date
Jun-2010
Author
Katri Kantojärvi
Päivi Onkamo
Raija Vanhala
Reija Alen
Minttu Hedman
Antti Sajantila
Taina Nieminen-von Wendt
Irma Järvelä
Author Affiliation
Department of Medical Genetics, University of Helsinki, Helsinki, Finland. katri.kantojarvi@helsinki.fi
Source
Psychiatr Genet. 2010 Jun;20(3):102-8
Date
Jun-2010
Language
English
Publication Type
Article
Keywords
Alleles
Child Development Disorders, Pervasive - genetics
Chromosomes, Human, Pair 11 - genetics
Chromosomes, Human, Pair 9 - genetics
Female
Finland
Genetic markers
Genetic Predisposition to Disease
Humans
Infant
Jumonji Domain-Containing Histone Demethylases - genetics
Linkage Disequilibrium - genetics
Male
Polymorphism, Single Nucleotide - genetics
Abstract
Autism spectrum disorders (ASD) often show obsessive repetitive symptoms that are characteristic to obsessive-compulsive disorder (OCD). Aberrant glutamate function has been suggested to a risk for both ASDs and OCD. Considering the common metabolic pathway and recent results from association studies both in OCD and ASDs, a question, whether there is common molecular background in ASDs and OCD, was raised.
Ten single nucleotide polymorphisms (SNPs) at 9p24 and 11p12-p13 containing glutamate transporter genes SLC1A1 and SLC1A2 and their neighboring regions in 175 patients with ASDs and 216 controls of Finnish origin were analyzed using real-time-PCR or direct sequencing.
The strongest association was detected with rs1340513 in the JMJD2C gene at 9p24.1 (P=0.007; corrected P=0.011) that is the same SNP associated with infantile autism (P=0.0007) in the autism genome project consortium (2007). No association was detected at 11p12-p13 with ASD. Interestingly, the strongest association in OCD has been found at rs301443 (P=0.000067) residing between SLC1A1 and JMJD2C at 9p24.
In summary, our results give evidence for a possible common locus for OCD and ASDs at 9p24. We speculate that the area may represent a special candidate region for obsessive repetitive symptoms in ASDs.
PubMed ID
20410850 View in PubMed
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Anxiety with panic disorder linked to chromosome 9q in Iceland.

https://arctichealth.org/en/permalink/ahliterature185955
Source
Am J Hum Genet. 2003 May;72(5):1221-30
Publication Type
Article
Date
May-2003
Author
Thorgeir E Thorgeirsson
Högni Oskarsson
Natasa Desnica
Jelena Pop Kostic
Jon G Stefansson
Halldor Kolbeinsson
Eirikur Lindal
Nikolai Gagunashvili
Michael L Frigge
Augustine Kong
Kari Stefansson
Jeffrey R Gulcher
Author Affiliation
deCode Genetics, Reykjavík, Iceland. thorgeir@decode.is
Source
Am J Hum Genet. 2003 May;72(5):1221-30
Date
May-2003
Language
English
Publication Type
Article
Keywords
Anxiety - diagnosis - epidemiology - genetics
Chromosome Mapping
Chromosomes, Human, Pair 9 - genetics
Comorbidity
Genetic Linkage
Genetic markers
Genetic Predisposition to Disease
Genotype
Humans
Iceland - epidemiology
Lod Score
Mass Screening
Microsatellite Repeats
Panic Disorder - diagnosis - epidemiology - genetics
Questionnaires
Abstract
The results of a genomewide scan for genes conferring susceptibility to anxiety disorders in the Icelandic population are described. The aim of the study was to locate genes that predispose to anxiety by utilizing the extensive genealogical records and the relative homogeneity of the Icelandic population. Participants were recruited in two stages: (1) Initial case-identification by a population screening for anxiety disorders, using the Stamm Screening Questionnaire, was followed by aggregation into extended families, with the help of our genealogy database; and (2) those who fulfilled the diagnostic and family aggregation criteria underwent a more detailed diagnostic workup based on the Composite International Diagnostic Interview. Screening for anxiety in close relatives also identified additional affected members within the families. After genotyping was performed with 976 microsatellite markers, affected-only linkage analysis was done, and allele-sharing LOD scores were calculated using the program Allegro. Linkage analysis of 25 extended families, in each of which at least one affected individual had panic disorder (PD), resulted in a LOD score of 4.18 at D9S271, on chromosome 9q31. The intermarker distance was 4.4 cM on average, whereas it was 1.5 cM in the linked region as additional markers were added to increase the information content. The linkage results may be relevant not only to PD but also to anxiety in general, since our linkage study included patients with other forms of anxiety.
Notes
Cites: J Child Psychol Psychiatry. 1999 Nov;40(8):1273-8210604405
Cites: Am J Med Genet. 1998 Mar 28;81(2):139-479613853
Cites: Am J Med Genet. 2000 Feb 7;96(1):24-3510686548
Cites: Eur J Hum Genet. 2000 Oct;8(10):739-4211039572
Cites: Behav Res Ther. 2001 Jan;39(1):89-10011125726
Cites: Br J Psychiatry. 2001 Feb;178:145-5311157427
Cites: Arch Gen Psychiatry. 2001 Mar;58(3):257-6511231833
Cites: Curr Psychiatry Rep. 2001 Apr;3(2):131-711276408
Cites: Behav Res Ther. 2001 Apr;39(4):443-5611280342
Cites: Acta Psychiatr Scand. 1993 Jul;88(1):29-348372693
Cites: Arch Gen Psychiatry. 1998 Oct;55(10):936-409783565
Cites: Clin Chem Lab Med. 1998 Aug;36(8):523-79806453
Cites: Br J Psychiatry Suppl. 1998;(34):4-99829010
Cites: Psychiatry Res. 1998 Nov 16;81(2):277-99858044
Cites: Mol Psychiatry. 1999 Mar;4(2):155-6210208447
Cites: Genome Res. 1999 Oct;9(10):1002-1210523529
Cites: Psychiatr Genet. 2000 Dec;10(4):191-411324945
Cites: Am J Med Genet. 2001 Jan 8;105(1):105-911424978
Cites: Mol Psychiatry. 2001 Jul;6(4):465-7011443535
Cites: Am J Med Genet. 2001 Aug 8;105(6):548-5711496373
Cites: Cell. 2001 Aug 10;106(3):367-7911509185
Cites: Am J Psychiatry. 2001 Oct;158(10):1568-7811578982
Cites: Behav Res Ther. 2001 Nov;39(11):1357-6811686270
Cites: Biol Psychiatry. 2002 Apr 1;51(7):591-60111950461
Cites: Nat Genet. 2002 Jul;31(3):241-712053178
Cites: Genet Epidemiol. 1984;1(2):109-226599401
Cites: Am J Hum Genet. 1988 Feb;42(2):315-263422543
Cites: Acta Psychiatr Scand. 1990 Feb;81(2):97-1072183544
Cites: Int J Soc Psychiatry. 1991 Winter;37(4):233-411783501
Cites: Acta Psychiatr Scand. 1993 Aug;88(2):85-928213211
Cites: Arch Gen Psychiatry. 1994 Jan;51(1):8-198279933
Cites: Biometrics. 1994 Mar;50(1):118-278086596
Cites: Arch Gen Psychiatry. 1995 May;52(5):374-837726718
Cites: Nat Genet. 1995 Nov;11(3):241-77581446
Cites: J Psychiatr Res. 1995 Nov-Dec;29(6):467-808642544
Cites: Am J Hum Genet. 1996 Jun;58(6):1347-638651312
Cites: Psychol Med. 1995 Nov;25(6):1269-808637956
Cites: Br J Psychiatry Suppl. 1996 Jun;(30):101-88864155
Cites: J Clin Psychiatry. 1996 Nov;57(11):528-338968302
Cites: Am J Hum Genet. 1997 Nov;61(5):1179-889345087
Cites: Annu Rev Psychol. 1998;49:377-4129496627
Cites: Nat Genet. 2000 May;25(1):12-310802644
PubMed ID
12679899 View in PubMed
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Ataxias on the march from Quebec to Tunisia.

https://arctichealth.org/en/permalink/ahliterature198966
Source
Neurology. 2000 Apr 11;54(7):1400-1
Publication Type
Article
Date
Apr-11-2000

Chromosome 9 ALS and FTD locus is probably derived from a single founder.

https://arctichealth.org/en/permalink/ahliterature131202
Source
Neurobiol Aging. 2012 Jan;33(1):209.e3-8
Publication Type
Article
Date
Jan-2012
Author
Kin Mok
Bryan J Traynor
Jennifer Schymick
Pentti J Tienari
Hannu Laaksovirta
Terhi Peuralinna
Liisa Myllykangas
Adriano Chiò
Aleksey Shatunov
Bradley F Boeve
Adam L Boxer
Mariely DeJesus-Hernandez
Ian R Mackenzie
Adrian Waite
Nigel Williams
Huw R Morris
Javier Simón-Sánchez
John C van Swieten
Peter Heutink
Gabriella Restagno
Gabriele Mora
Karen E Morrison
Pamela J Shaw
Pamela Sara Rollinson
Ammar Al-Chalabi
Rosa Rademakers
Stuart Pickering-Brown
Richard W Orrell
Michael A Nalls
John Hardy
Author Affiliation
Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
Source
Neurobiol Aging. 2012 Jan;33(1):209.e3-8
Date
Jan-2012
Language
English
Publication Type
Article
Keywords
Amyotrophic Lateral Sclerosis - genetics
Chromosomes, Human, Pair 9 - genetics
Finland
Frontotemporal Dementia - genetics
Genetic Linkage
Genome-Wide Association Study
Haplotypes
Humans
Polymorphism, Single Nucleotide
Abstract
We and others have recently reported an association between amyotrophic lateral sclerosis (ALS) and single nucleotide polymorphisms on chromosome 9p21 in several populations. Here we show that the associated haplotype is the same in all populations and that several families previously shown to have genetic linkage to this region also share this haplotype. The most parsimonious explanation of these data are that there is a single founder for this form of disease.
Notes
Cites: J Neurol Neurosurg Psychiatry. 2011 Feb;82(2):196-20320562461
Cites: Lancet Neurol. 2010 Oct;9(10):986-9420801717
Cites: Neurobiol Aging. 2011 Apr;32(4):758.e1-721257233
Cites: J Neurol Neurosurg Psychiatry. 2011 May;82(5):476-8620971753
Cites: Nat Genet. 2001 Aug;28(4):309-1011479587
Cites: Brain. 2002 Apr;125(Pt 4):732-5111912108
Cites: Bioinformatics. 2005 Jan 15;21(2):263-515297300
Cites: Brain. 2006 Apr;129(Pt 4):868-7616495328
Cites: Neurology. 2006 Mar 28;66(6):839-4416421333
Cites: Lancet Neurol. 2007 Apr;6(4):322-817362836
Cites: Am J Hum Genet. 2007 Sep;81(3):559-7517701901
Cites: Hum Mol Genet. 2008 Mar 1;17(5):768-7418057069
Cites: Hum Mol Genet. 2009 Apr 15;18(8):1524-3219193627
Cites: Nat Genet. 2009 Oct;41(10):1083-719734901
Cites: Nat Genet. 2010 Mar;42(3):234-920154673
Cites: Arch Neurol. 2010 May;67(5):606-1620457961
Cites: Bioinformatics. 2010 Sep 1;26(17):2190-120616382
Cites: Nature. 2010 Sep 2;467(7311):52-820811451
Cites: J Neurol. 2011 Apr;258(4):647-5521072532
PubMed ID
21925771 View in PubMed
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Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide association study.

https://arctichealth.org/en/permalink/ahliterature141194
Source
Lancet Neurol. 2010 Oct;9(10):978-85
Publication Type
Article
Date
Oct-2010
Author
Hannu Laaksovirta
Terhi Peuralinna
Jennifer C Schymick
Sonja W Scholz
Shaoi-Lin Lai
Liisa Myllykangas
Raimo Sulkava
Lilja Jansson
Dena G Hernandez
J Raphael Gibbs
Michael A Nalls
David Heckerman
Pentti J Tienari
Bryan J Traynor
Author Affiliation
Department of Neurology, Helsinki University Central Hospital and Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki, Finland.
Source
Lancet Neurol. 2010 Oct;9(10):978-85
Date
Oct-2010
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Amyotrophic Lateral Sclerosis - enzymology - epidemiology - genetics
Chromosomes, Human, Pair 9 - genetics
Cohort Studies
Female
Finland - epidemiology
Genetic Loci - genetics
Genetic Predisposition to Disease - epidemiology - genetics
Genome-Wide Association Study - methods
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide - genetics
Superoxide Dismutase - genetics
Young Adult
Abstract
The genetic cause of amyotrophic lateral sclerosis (ALS) is not well understood. Finland is a well suited location for a genome-wide association study of ALS because the incidence of the disease is one of the highest in the world, and because the genetic homogeneity of the Finnish population enhances the ability to detect risk loci. We aimed to identify genetic risk factors for ALS in the Finnish population.
We did a genome-wide association study of Finnish patients with ALS and control individuals by use of Illumina genome-wide genotyping arrays. DNA was collected from patients who attended an ALS specialty clinic that receives referrals from neurologists throughout Finland. Control samples were from a population-based study of elderly Finnish individuals. Patients known to carry D90A alleles of the SOD1 gene (n=40) were included in the final analysis as positive controls to assess whether our genome-wide association study was able to detect an association signal at this locus.
We obtained samples from 442 patients with ALS and 521 control individuals. After quality control filters were applied, 318?167 single nucleotide polymorphisms (SNPs) from 405 people with ALS and 497 control individuals were available for analysis. We identified two association peaks that exceeded genome-wide significance. One was located on chromosome 21q22 (rs13048019, p=2·58×10(-8)), which corresponds to the autosomal recessive D90A allele of the SOD1 gene. The other was detected in a 232 kb block of linkage disequilibrium (rs3849942, p=9·11×10(-11)) in a region of chromosome 9p that was previously identified in linkage studies of families with ALS. Within this region, we defined a 42-SNP haplotype that was associated with significantly increased risk of ALS (p=7·47×10(-33) when people with familial ALS were compared with controls, odds ratio 21·0, 95% CI 11·2-39·1) and which overlapped with an association locus recently reported for frontotemporal dementia. For the 93 patients with familial ALS, the population attributable risk for the chromosome 9p21 locus was 37·9% (95% CI 27·7-48·1) and that for D90A homozygosity was 25·5% (16·9-34·1).
The chromosome 9p21 locus is a major cause of familial ALS in the Finnish population. Our data suggest the presence of a founder mutation for chromosome 9p21-linked ALS. Furthermore, the overlap with the risk haplotype recently reported for frontotemporal dementia provides further evidence of a shared genetic cause for these two neurodegenerative diseases.
National Institutes of Health and National Institute on Aging, Microsoft Research, ALS Association, Helsinki University Central Hospital, Finnish Academy, Finnish Medical Society Duodecim, and Kuopio University.
Notes
Cites: Bioinformatics. 2005 Jan 15;21(2):263-515297300
Cites: Brain. 2006 Apr;129(Pt 4):868-7616495328
Cites: Neurology. 2006 Mar 28;66(6):839-4416421333
Cites: Arch Neurol. 2007 Feb;64(2):240-517296840
Cites: Neurology. 2007 Feb 20;68(8):600-217310031
Cites: Lancet Neurol. 2007 Apr;6(4):322-817362836
Cites: Neurology. 2007 Mar 27;68(13):1002-717389304
Cites: Am J Hum Genet. 2007 Sep;81(3):559-7517701901
Cites: N Engl J Med. 2007 Aug 23;357(8):775-8817671248
Cites: Lancet Neurol. 2007 Oct;6(10):869-7717827064
Cites: Nat Genet. 2008 Jan;40(1):29-3118084291
Cites: Am J Hum Genet. 2008 Feb;82(2):453-6318252225
Cites: Hum Mol Genet. 2008 Mar 1;17(5):768-7418057069
Cites: BMC Neurol. 2008;8:3218755042
Cites: Hum Mol Genet. 2009 Apr 15;18(8):1524-3219193627
Cites: Neurology. 2009 May 12;72(19):1669-7619433740
Cites: Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):9004-919451621
Cites: Nat Genet. 2010 Mar;42(3):234-920154673
Cites: J Neurol Neurosurg Psychiatry. 2011 Feb;82(2):196-20320562461
Cites: N Engl J Med. 2001 May 31;344(22):1688-70011386269
Cites: Neurology. 2001 Jun 26;56(12):1690-611425935
Cites: Nat Genet. 2001 Aug;28(4):309-1011479587
Cites: Annu Rev Genomics Hum Genet. 2001;2:103-2811701645
Cites: J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):867-7112810769
Cites: Int J Epidemiol. 1978 Jun;7(2):175-82681063
Cites: Acta Neurol Scand. 1983 Jan;67(1):41-76601351
Cites: J Neurol Sci. 1994 Jul;124 Suppl:96-1077807156
Cites: Nat Genet. 1995 May;10(1):61-67647793
Cites: Neuropathol Appl Neurobiol. 1998 Apr;24(2):104-179634206
Cites: Hum Mol Genet. 1999;8(10):1913-2310469845
Comment In: Lancet Neurol. 2010 Oct;9(10):945-720801719
PubMed ID
20801718 View in PubMed
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Clinical and histopathological features of malignant melanoma in germline CDKN2A mutation families.

https://arctichealth.org/en/permalink/ahliterature18759
Source
Melanoma Res. 2002 Dec;12(6):549-57
Publication Type
Article
Date
Dec-2002
Author
A. Måsbäck
H. Olsson
J. Westerdahl
T. Sandberg
A. Borg
N. Jonsson
C. Ingvar
Author Affiliation
Department of Pathology, University Hospital, Lund, Sweden. anna.masback@skane.se
Source
Melanoma Res. 2002 Dec;12(6):549-57
Date
Dec-2002
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Case-Control Studies
Chromosomes, Human, Pair 9 - genetics
Comparative Study
DNA Mutational Analysis
DNA, Neoplasm - analysis
Female
Genes, p16
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Male
Matched-Pair Analysis
Melanoma - epidemiology - genetics - pathology
Middle Aged
Multivariate Analysis
Odds Ratio
Skin Neoplasms - epidemiology - genetics - pathology
Survival Analysis
Sweden - epidemiology
Abstract
Primary cutaneous malignant melanomas (CMMs) from 26 individuals belonging to nine families with an identified mutation were clinically and histopathologically compared with 78 matched CMM controls and with a population-based series of CMMs ( = 667). All tumours were histopathologically re-examined. CDKN2A-associated cases were significantly less invasive compared with the matched controls, with an adjusted odds ratio (adjOR) of 2.9 and a 95% confidence interval (CI) of 1.0-8.1 ( = 0.04). According to the odds ratio (OR) values, CDKN2A-associated cases seemed to have tumours more often located on the head and neck (adjOR 2.9, 95% CI 0.6-13.7), with less inflammation (adjOR 0.7, 95% CI 0.3-1.8) and regression (adjOR 0.6, 95% CI 0.2-1.8) but more frequent histological ulceration (adjOR 1.9, 95% CI 0.6-5.8). In comparison with the population-based material, CDKN2A-associated cases were significantly younger at diagnosis (crude OR 3.5, 95% CI 1.6-7.5, divided at 50 years) and had less regressive reaction in their tumours (crude OR 0.35, 95% CI 0.2-0.8). No significant differences were seen for tumour thickness between the different groups. On multivariate analysis, the overall survival was significantly worse for thicker tumours and older age ( = 0.04 for both). To our knowledge this is the first description of the histopathological features of CMMs from families with mutations in the CDKN2A gene.
PubMed ID
12459644 View in PubMed
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Common genetic variants on chromosome 9p21 confers risk of ischemic stroke: a large-scale genetic association study.

https://arctichealth.org/en/permalink/ahliterature98531
Source
Circ Cardiovasc Genet. 2009 Apr;2(2):159-64
Publication Type
Article
Date
Apr-2009
Author
J Gustav Smith
Olle Melander
Håkan Lövkvist
Bo Hedblad
Gunnar Engström
Peter Nilsson
Joyce Carlson
Göran Berglund
Bo Norrving
Arne Lindgren
Author Affiliation
Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Source
Circ Cardiovasc Genet. 2009 Apr;2(2):159-64
Date
Apr-2009
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Case-Control Studies
Chromosomes, Human, Pair 9 - genetics
Female
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Humans
Ischemia - genetics
Male
Middle Aged
Polymorphism, Single Nucleotide
Prospective Studies
Risk factors
Stroke - genetics
Sweden
Abstract
BACKGROUND: Epidemiological studies indicate a genetic contribution to ischemic stroke risk, but specific genetic variants remain unknown, with the exception of a few rare variants. Recent genome-wide association studies identified and replicated common genetic variants on chromosome 9p21 to confer risk of coronary heart disease. We examined whether these variants are associated with ischemic stroke. METHODS AND RESULTS: We genotyped 6 common genetic variants on chromosome 9p21, previously associated with coronary artery disease in genome-wide association studies, in 2 population-based studies in southern Sweden, the Lund Stroke Register (n=1837 cases, 947 controls) and the Malmö Diet and Cancer study (MDC; n=888 cases, 893 controls). We examined association in each study and in the pooled dataset. Adjustments were made for cardiovascular risk factors and further for previous myocardial infarction in MDC. We found a modest increase in ischemic stroke risk for 2 common (minor allele frequencies 0.46 to 0.49) variants, rs2383207 (P=0.04 in Lund Stroke Register, P=0.01 in MDC) and rs10757274 (P=0.03 in Lund Stroke Register, P=0.03 in MDC), in each sample independently. The strength of the association increased when samples were pooled with an odds ratio of 1.15 (95% CI, 1.05 to 1.25; P=0.002) for the strongest variant rs2383207. Results were similar after adjustment for clinical covariates. rs1333049 also showed significant association in MDC, which increased in the pooled sample (P=0.004). CONCLUSIONS: In this large sample (n=4565), we detected common genetic determinants for ischemic stroke on chromosome 9p21. Our findings indicate that ischemic stroke shares pathophysiological determinants with coronary heart disease and other arterial diseases and highlight the need for large sample sizes in stroke genetics.
PubMed ID
20031580 View in PubMed
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Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients.

https://arctichealth.org/en/permalink/ahliterature79813
Source
Eur J Hum Genet. 2007 Feb;15(2):143-9
Publication Type
Article
Date
Feb-2007
Author
Schoumans Jacqueline
Wincent Josephine
Barbaro Michela
Djureinovic Tatjana
Maguire Paula
Forsberg Lena
Staaf Johan
Thuresson Ann Charlotte
Borg Ake
Nordgren Ann
Malm Gunilla
Anderlid Britt Marie
Author Affiliation
Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital Solna, Stockholm, Sweden. jacqueline.schoumans@ki.se
Source
Eur J Hum Genet. 2007 Feb;15(2):143-9
Date
Feb-2007
Language
English
Publication Type
Article
Keywords
5' Untranslated Regions - genetics
Adolescent
Cell Cycle Proteins - genetics
Child
Chromosomal Instability
Chromosomal Proteins, Non-Histone - genetics
Chromosomes, Human, Pair 9 - genetics
Cohort Studies
DNA Mutational Analysis
De Lange Syndrome - genetics
Female
Humans
Male
Mutation
Nucleic Acid Hybridization
Phenotype
Proteins - genetics
Sweden
Abstract
Cornelia de Lange syndrome (CdLS; OMIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by distinctive dysmorphic facial features, severe growth and developmental delay and abnormalities of the upper limbs. About 50% of CdLS patients have been found to have heterozygous mutations in the NIPBL gene and a few cases were recently found to be caused by mutations in the X-linked SMC1L1 gene. We performed a mutation screening of all NIPBL coding exons by direct sequencing in 11 patients (nine sporadic and two familial cases) diagnosed with CdLS in Sweden and detected mutations in seven of the cases. All were de novo, and six of the mutations have not been previously described. Four patients without identifiable NIPBL mutations were subsequently subjected to multiplex ligation-dependent probe amplification analysis to exclude whole exon deletions/duplications of NIPBL. In addition, mutation analysis of the 5' untranslated region (5' UTR) of NIPBL was performed. Tiling resolution array comparative genomic hybridization analysis was carried out on these four patients to detect cryptic chromosome imbalances and in addition the boys were screened for SMC1L1 mutations. We found a de novo 9p duplication with a size of 0.6 Mb in one of the patients with a CdLS-like phenotype but no mutations were detected in SMC1L1. So far, two genes (NIPBL and SMC1L1) have been identified causing CdLS or CdLS-like phenotypes. However, in a considerable proportion of individuals demonstrating the CdLS phenotype, mutations in any of these two genes are not found and other potential loci harboring additional CdLS-causing genes should be considered.
PubMed ID
17106445 View in PubMed
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Evidence for additional FREM1 heterogeneity in Manitoba oculotrichoanal syndrome.

https://arctichealth.org/en/permalink/ahliterature123522
Source
Mol Vis. 2012;18:1301-11
Publication Type
Article
Date
2012
Author
Robertino Karlo Mateo
Royce Johnson
Ordan J Lehmann
Author Affiliation
Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada. robertin@ualberta.ca
Source
Mol Vis. 2012;18:1301-11
Date
2012
Language
English
Publication Type
Article
Keywords
Abnormalities, Multiple - genetics - pathology
Adult
Alleles
Anal Canal - abnormalities - pathology
Child, Preschool
Chromosomes, Human, Pair 9 - genetics
Coloboma - genetics - pathology
Ethnic Groups - genetics
Female
Founder Effect
Gene Frequency
Genetic Heterogeneity
Genotype
Homozygote
Humans
Hypertelorism - genetics - pathology
Linkage Disequilibrium
Manitoba
Pedigree
Phenotype
Polymorphism, Single Nucleotide
Receptors, Interleukin - genetics
Sequence Analysis, DNA
Severity of Illness Index
Abstract
Manitoba Oculotrichoanal (MOTA) syndrome is an autosomal recessive disorder present in First Nations families that is characterized by ocular (cryptophthalmos), facial, and genital anomalies. At the commencement of this study, its genetic basis was undefined.
Homozygosity analysis was employed to map the causative locus using DNA samples from four probands of Cree ancestry. After single nucleotide polymorphism (SNP) genotyping, data were analyzed and exported to PLINK to identify regions identical by descent (IBD) and common to the probands. Candidate genes within and adjacent to the IBD interval were sequenced to identify pathogenic variants, with analyses of potential deletions or duplications undertaken using the B-allele frequency and log(2) ratio of SNP signal intensity.
Although no shared IBD region >1 Mb was evident on preliminary analysis, adjusting the criteria to permit the detection of smaller homozygous IBD regions revealed one 330 Kb segment on chromosome 9p22.3 present in all 4 probands. This interval comprising 152 SNPs, lies 16 Kb downstream of FRAS1-related extracellular matrix protein 1 (FREM1), and no copy number variations were detected either in the IBD region or FREM1. Subsequent sequencing of both genes in the IBD region, followed by FREM1, did not reveal any mutations.
This study illustrates the utility of studying geographically isolated populations to identify genomic regions responsible for disease through analysis of small numbers of affected individuals. The location of the IBD region 16 kb from FREM1 suggests the phenotype in these patients is attributable to a variant outside of FREM1, potentially in a regulatory element, whose identification may prove tractable to next generation sequencing. In the context of recent identification of FREM1 coding mutations in a proportion of MOTA cases, characterization of such additional variants offers scope both to enhance understanding of FREM1's role in cranio-facial biology and may facilitate genetic counselling in populations with high prevalences of MOTA to reduce the incidence of this disorder.
Notes
Cites: Am J Med Genet A. 2008 Sep 1;146A(17):2252-718671281
Cites: Genome Res. 2008 Feb;18(2):201-518245453
Cites: Am J Hum Genet. 2009 Sep;85(3):414-819732862
Cites: PLoS Genet. 2009 Nov;5(11):e100074819956733
Cites: Hum Genet. 2010 Feb;127(2):231-4119911200
Cites: Annu Rev Genomics Hum Genet. 2010;11:1-2320438361
Cites: Invest Ophthalmol Vis Sci. 2010 Nov;51(11):5943-5120554613
Cites: Int J Biochem Cell Biol. 2011 Apr;43(4):487-9521182980
Cites: J Med Genet. 2011 Jun;48(6):375-8221507892
Cites: PLoS Genet. 2011 Sep;7(9):e100227821931569
Cites: J Med Genet. 2012 May;49(5):303-622510445
Cites: Am J Hum Genet. 1999 Dec;65(6):1493-50010577902
Cites: Genesis. 2000 Apr;26(4):265-7010748465
Cites: Hum Mol Genet. 2001 Sep 15;10(19):2049-5911590122
Cites: Genome Res. 2002 Jun;12(6):996-100612045153
Cites: J Med Genet. 2002 Sep;39(9):623-3312205104
Cites: Nat Genet. 2003 Jun;34(2):203-812766769
Cites: Nat Genet. 2004 Feb;36(2):172-714730302
Cites: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W280-615215395
Cites: Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13560-515345741
Cites: Acta Ophthalmol (Copenh). 1966;44(1):84-944958085
Cites: J Hered. 1981 Jul-Aug;72(4):2936793660
Cites: Science. 1987 Jun 19;236(4808):1567-702884728
Cites: Am J Med Genet. 1992 Apr 1;42(6):793-91554017
Cites: Hum Mol Genet. 1995 Mar;4(3):415-227795596
Cites: J Biol Chem. 1996 Oct 18;271(42):26110-68824254
Cites: Genomics. 1998 Aug 1;51(3):325-319721202
Cites: J Biol Chem. 1999 Jun 11;274(24):16831-710358027
Cites: Nat Genet. 2005 May;37(5):520-515838507
Cites: Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11746-5016087869
Cites: Hum Mol Genet. 2005 Oct 15;14 Spec No. 2:R269-7416244325
Cites: Mol Cell Biol. 2006 Apr;26(8):3308-1816581802
Cites: Am J Hum Genet. 2006 May;78(5):889-9616642444
Cites: Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11981-616880404
Cites: Nucleic Acids Res. 2007 Jan;35(Database issue):D88-9217130149
Cites: Am J Med Genet A. 2007 Feb 1;143(3):241-717163535
Cites: Gene Expr Patterns. 2007 Feb;7(4):381-817251066
Cites: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3255-6017360634
Cites: Am J Med Genet A. 2007 Apr 15;143A(8):853-717352387
Cites: IUBMB Life. 2007 Jul;59(7):427-3517654118
Cites: Am J Hum Genet. 2007 Sep;81(3):559-7517701901
Cites: Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5690-818055821
Cites: J Mol Biol. 2008 Feb 1;375(5):1457-6818155042
Cites: Am J Med Genet A. 2008 Feb 15;146A(4):529-3118203166
Cites: Am J Hum Genet. 2009 Aug;85(2):240-719615668
PubMed ID
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