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Zander, C
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Publications (10 of 12) Show all publications
Thuresson, A.-C., Zander, C., Zhao, J. J., Halvardson, J., Maqbool, K., Månsson, E., . . . Feuk, L. (2019). Whole genome sequencing of consanguineous families reveals novel pathogenic variants in intellectual disability [Letter to the editor]. Clinical Genetics, 95(3), 436-439
Open this publication in new window or tab >>Whole genome sequencing of consanguineous families reveals novel pathogenic variants in intellectual disability
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2019 (English)In: Clinical Genetics, ISSN 0009-9163, E-ISSN 1399-0004, Vol. 95, no 3, p. 436-439Article in journal, Letter (Refereed) Published
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-326281 (URN)10.1111/cge.13470 (DOI)000458956100013 ()30525197 (PubMedID)
Funder
EU, European Research Council, 282330
Available from: 2017-07-04 Created: 2017-07-04 Last updated: 2019-03-14Bibliographically approved
Zhao, J. J., Halvardson, J., Zander, C., Zaghlool, A., Georgii-Hemming, P., Månsson, E., . . . Feuk, L. (2018). Exome sequencing reveals NAA15 and PUF60 as candidate genes associated with intellectual disability. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 177(1), 10-20
Open this publication in new window or tab >>Exome sequencing reveals NAA15 and PUF60 as candidate genes associated with intellectual disability
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2018 (English)In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-4841, E-ISSN 1552-485X, Vol. 177, no 1, p. 10-20Article in journal (Refereed) Published
Abstract [en]

Intellectual Disability (ID) is a clinically heterogeneous condition that affects 2-3% of population worldwide. In recent years, exome sequencing has been a successful strategy for studies of genetic causes of ID, providing a growing list of both candidate and validated ID genes. In this study, exome sequencing was performed on 28 ID patients in 27 patient-parent trios with the aim to identify de novo variants (DNVs) in known and novel ID associated genes. We report the identification of 25 DNVs out of which five were classified as pathogenic or likely pathogenic. Among these, a two base pair deletion was identified in the PUF60 gene, which is one of three genes in the critical region of the 8q24.3 microdeletion syndrome (Verheij syndrome). Our result adds to the growing evidence that PUF60 is responsible for the majority of the symptoms reported for carriers of a microdeletion across this region. We also report variants in several genes previously not associated with ID, including a de novo missense variant in NAA15. We highlight NAA15 as a novel candidate ID gene based on the vital role of NAA15 in the generation and differentiation of neurons in neonatal brain, the fact that the gene is highly intolerant to loss of function and coding variation, and previously reported DNVs in neurodevelopmental disorders.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-326280 (URN)10.1002/ajmg.b.32574 (DOI)000417876700002 ()28990276 (PubMedID)
Funder
EU, European Research Council
Available from: 2017-07-04 Created: 2017-07-04 Last updated: 2018-01-17Bibliographically approved
Thuresson, A.-C., Van Buggenhout, G., Sheth, F., Kamate, M., Andrieux, J., Clayton Smith, J. & Zander, C. S. (2017). Whole-gene duplication of SCN2A and SCN3A is associated with neonatal seizures and a normal intellectual development. Clinical Genetics, 91(1), 106-110
Open this publication in new window or tab >>Whole-gene duplication of SCN2A and SCN3A is associated with neonatal seizures and a normal intellectual development
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2017 (English)In: Clinical Genetics, ISSN 0009-9163, E-ISSN 1399-0004, Vol. 91, no 1, p. 106-110Article in journal (Refereed) Published
Abstract [en]

Duplications at 2q24.3 encompassing the voltage-gated sodium channel gene cluster are associated with early onset epilepsy. All cases described in the literature have presented in addition with different degrees of intellectual disability, and have involved neighbouring genes in addition to the sodium channel gene cluster. Here we report eight new cases with overlapping duplications at 2q24 ranging from 0.05 Mb to 7.63 Mb in size. Taken together with the previously reported cases, our study suggests that having an extra copy of SCN2A has an effect on epilepsy pathogenesis, causing benign familial infantile seizures which eventually disappear at the age of one to two years.. However, the number of copies of SCN2A does not appear to have an effect on cognitive outcome.

Keywords
2q24 duplication, benign familial neonatal-infantile seizures, neonatal epilepsy, SCN2A, voltage-gated sodium channel
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-302318 (URN)10.1111/cge.12797 (DOI)000393979600014 ()27153334 (PubMedID)
Funder
Wellcome trust, HICF-1009-003 WT098051
Available from: 2016-08-31 Created: 2016-08-31 Last updated: 2018-01-10Bibliographically approved
Halvardson, J., Zhao, J. J., Zaghlool, A., Wentzel, C., Georgii-Hemming, P., Månsson, E., . . . Feuk, L. (2016). Mutations in HECW2 are associated with intellectual disability and epilepsy. Journal of Medical Genetics, 53(10), 697-704
Open this publication in new window or tab >>Mutations in HECW2 are associated with intellectual disability and epilepsy
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2016 (English)In: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 53, no 10, p. 697-704Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: De novo mutations are a frequent cause of disorders related to brain development. We report the results of screening patients diagnosed with both epilepsy and intellectual disability (ID) using exome sequencing to identify known and new causative de novo mutations relevant to these conditions.

METHODS: Exome sequencing was performed on 39 patient-parent trios to identify de novo mutations. Clinical significance of de novo mutations in genes was determined using the American College of Medical Genetics and Genomics standard guidelines for interpretation of coding variants. Variants in genes of unknown clinical significance were further analysed in the context of previous trio sequencing efforts in neurodevelopmental disorders.

RESULTS: In 39 patient-parent trios we identified 29 de novo mutations in coding sequence. Analysis of de novo and inherited variants yielded a molecular diagnosis in 11 families (28.2%). In combination with previously published exome sequencing results in neurodevelopmental disorders, our analysis implicates HECW2 as a novel candidate gene in ID and epilepsy.

CONCLUSIONS: Our results support the use of exome sequencing as a diagnostic approach for ID and epilepsy, and confirm previous results regarding the importance of de novo mutations in this patient group. The results also highlight the utility of network analysis and comparison to previous large-scale studies as strategies to prioritise candidate genes for further studies. This study adds knowledge to the increasingly growing list of causative and candidate genes in ID and epilepsy and highlights HECW2 as a new candidate gene for neurodevelopmental disorders.

Keywords
Intellectual disability; Epilepsy; Exome sequencing; HECW2; ERC2
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-301393 (URN)10.1136/jmedgenet-2016-103814 (DOI)000385958500008 ()27334371 (PubMedID)
Funder
EU, European Research Council, 282330Swedish Society for Medical Research (SSMF)
Available from: 2016-08-31 Created: 2016-08-22 Last updated: 2018-01-10Bibliographically approved
Zander, C. S. (2015). Beckwith-Wiedemann Syndrome Revisited.. Human Mutation, 36(9)
Open this publication in new window or tab >>Beckwith-Wiedemann Syndrome Revisited.
2015 (English)In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 36, no 9Article in journal (Refereed) Published
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-302319 (URN)10.1002/humu.22662 (DOI)26270560 (PubMedID)
External cooperation:
Available from: 2016-08-31 Created: 2016-08-31 Last updated: 2018-01-10Bibliographically approved
Englund, A., Jonsson, B., Zander, C. S., Gustafsson, J. & Annerén, G. (2013). Changes in mortality and causes of death in the Swedish Down syndrome population. American Journal of Medical Genetics. Part A, 161A(4), 642-649
Open this publication in new window or tab >>Changes in mortality and causes of death in the Swedish Down syndrome population
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2013 (English)In: American Journal of Medical Genetics. Part A, ISSN 1552-4825, E-ISSN 1552-4833, Vol. 161A, no 4, p. 642-649Article in journal (Refereed) Published
Abstract [en]

During the past few decades age at death for individuals with Down syndrome (DS) has increased dramatically. The birth frequency of infants with DS has long been constant in Sweden. Thus, the prevalence of DS in the population is increasing. The aim of the present study was to analyze mortality and causes of death in individuals with DS during the period 19692003. All individuals with DS that died between 1969 and 2003 in Sweden, and all individuals born with DS in Sweden between 1974 and 2003 were included. Data were obtained from the Swedish Medical Birth Register, the Swedish Birth Defects Register, and the National Cause of Death Register. Median age at death has increased by 1.8 years per year. The main cause of death was pneumonia. Death from congenital heart defects decreased. Death from atherosclerosis was rare but more frequent than reported previously. Dementia was not reported in any subjects with DS before 40 years of age, but was a main or contributing cause of death in 30% of the older subjects. Except for childhood leukemia, cancer as a cause of death was rare in all age groups. Mortality in DS, particularly infant mortality, has decreased markedly during the past decades. Median age at death is increasing and is now almost 60 years. Death from cancer is rare in DS, but death from dementia is common.

Keywords
Down syndrome, mortality, morbidity, epidemiology, trends, causes of death
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-199710 (URN)10.1002/ajmg.a.35706 (DOI)000316631300003 ()
Available from: 2013-05-13 Created: 2013-05-13 Last updated: 2017-12-06Bibliographically approved
Thierry, G., Beneteau, C., Pichon, O., Flori, E., Isidor, B., Popelard, F., . . . Le Caignec, C. (2012). Molecular characterization of 1q44 microdeletion in 11 patients reveals three candidate genes for intellectual disability and seizures. American Journal of Medical Genetics. Part A, 158A(7), 1633-1640
Open this publication in new window or tab >>Molecular characterization of 1q44 microdeletion in 11 patients reveals three candidate genes for intellectual disability and seizures
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2012 (English)In: American Journal of Medical Genetics. Part A, ISSN 1552-4825, E-ISSN 1552-4833, Vol. 158A, no 7, p. 1633-1640Article in journal (Refereed) Published
Abstract [en]

Patients with a submicroscopic deletion at 1q43q44 present with intellectual disability (ID), microcephaly, craniofacial anomalies, seizures, limb anomalies, and corpus callosum abnormalities. However, the precise relationship between most of deleted genes and the clinical features in these patients still remains unclear. We studied 11 unrelated patients with 1q44 microdeletion. We showed that the deletions occurred de novo in all patients for whom both parents' DNA was available (10/11). All patients presented with moderate to severe ID, seizures and non-specific craniofacial anomalies. By oligoarray-based comparative genomic hybridization (aCGH) covering the 1q44 region at a high resolution, we obtained a critical deleted region containing two coding genesHNRNPU and FAM36Aand one non-coding geneNCRNA00201. All three genes were expressed in different normal human tissues, including in human brain, with highest expression levels in the cerebellum. Mutational screening of the HNRNPU and FAM36A genes in 191 patients with unexplained isolated ID did not reveal any deleterious mutations while the NCRNA00201 non-coding gene was not analyzed. Nine of the 11 patients did not present with microcephaly or corpus callosum abnormalities and carried a small deletion containing HNRNPU, FAM36A, and NCRNA00201 but not AKT3 and ZNF238, two centromeric genes. These results suggest that HNRNPU, FAM36A, and NCRNA00201 are not major genes for microcephaly and corpus callosum abnormalities but are good candidates for ID and seizures. 

Keywords
1q44, deletion, chromosome, HNRNPU, FAM36A, ncRNA, intellectual disability, corpus callosum, seizure
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-177559 (URN)10.1002/ajmg.a.35423 (DOI)000305327000019 ()
Available from: 2012-07-16 Created: 2012-07-16 Last updated: 2018-01-12Bibliographically approved
Yuan, Q. P., Lindblad-Toh, K., Zander, C., Burgess, C., Durr, A. & Schalling, M. (2001). A cloning strategy for identification of genes containing trinucleotide repeat expansions. International Journal of Molecular Medicine, 8(4), 427-431
Open this publication in new window or tab >>A cloning strategy for identification of genes containing trinucleotide repeat expansions
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2001 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 8, no 4, p. 427-431Article in journal (Refereed) Published
Abstract [en]

Until today, nineteen trinucleotide repeat expansions larger than forty repeat copies have been found in the human genome. Of these, the CAG/CTG repeat is predominant motif with twelve loci identified, ten of which have been associated with the development of neurodegenerative diseases. We have developed a cloning approach which isolates disease genes containing trinucleotide repeat expansions. The method is based on size separation of genomic fragments, followed by subcloning and library hybridization with an oligonucleotide probe. Fractions and clones containing expanded repeats are identified by the repeat expansion detection (RED) method throughout the cloning procedure. Large family materials are not required and as little as 10 microg genomic DNA from a single individual is sufficient for this method. Using this strategy we have cloned two DNA fragments containing expanded repeats from two unrelated patients with a clinical diagnosis of cerebellar ataxia. Sequencing of the two fragments showed sequence identities with two disease genes, the Huntington gene and the ataxin 3 gene, respectively. The method should be adaptable to the cloning of any long repeat motif in any species. Furthermore the experimental steps can be performed in less than a month, making it very effective and time efficient to disease gene identification.

Keywords
Cerebellar Ataxia/genetics, Cloning; Molecular/*methods, DNA/chemistry/genetics, Databases; Nucleic Acid, Genes/*genetics, Humans, Nerve Tissue Proteins/genetics, Nuclear Proteins/genetics, Repressor Proteins, Sequence Analysis; DNA, Trinucleotide Repeat Expansion/*genetics
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-17316 (URN)11562783 (PubMedID)
Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2017-12-08Bibliographically approved
Lebre, A. S., Jamot, L., Takahashi, J., Spassky, N., Leprince, C., Ravisé, N., . . . Brice, A. (2001). Ataxin-7 interacts with a Cbl-associated protein that it recruits into neuronal intranuclear inclusions.. Hum Mol Genet, 10(11), 1201-13
Open this publication in new window or tab >>Ataxin-7 interacts with a Cbl-associated protein that it recruits into neuronal intranuclear inclusions.
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2001 (English)In: Hum Mol Genet, ISSN 0964-6906, Vol. 10, no 11, p. 1201-13Article in journal (Refereed) Published
Keywords
Alternative Splicing/*genetics, Amino Acid Sequence, Animals, Blotting; Northern, Blotting; Western, Brain/cytology/*metabolism, COS Cells/metabolism, Cell Nucleus/*metabolism, Cytoskeletal Proteins/genetics/*metabolism, Fluorescent Antibody Technique, Glutathione Transferase/metabolism, Haplorhini, Humans, Immunoenzyme Techniques, In Situ Hybridization; Fluorescence, Inclusion Bodies/metabolism, Mice, Microfilament Proteins/*metabolism, Molecular Sequence Data, Nerve Tissue Proteins/genetics/*metabolism, Neurons/*physiology, Precipitin Tests, Protein Isoforms, RNA; Messenger/*metabolism, Sequence Homology; Amino Acid, Two-Hybrid System Techniques, Yeasts/metabolism, beta-Galactosidase/metabolism
Identifiers
urn:nbn:se:uu:diva-17317 (URN)11371513 (PubMedID)
Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2011-01-13
Fujigasaki, H., Verma, I. C., Camuzat, A., Margolis, R. L., Zander, C., Lebre, A. S., . . . Brice, A. (2001). SCA12 is a rare locus for autosomal dominant cerebellar ataxia: a study of an Indian family.. Ann Neurol, 49(1), 117-21
Open this publication in new window or tab >>SCA12 is a rare locus for autosomal dominant cerebellar ataxia: a study of an Indian family.
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2001 (English)In: Ann Neurol, ISSN 0364-5134, Vol. 49, no 1, p. 117-21Article in journal (Refereed) Published
Keywords
Adult, Aged, Alleles, Cerebellar Ataxia/*genetics, Female, France, Humans, India, Male, Middle Aged, Pedigree, Trinucleotide Repeat Expansion/genetics
Identifiers
urn:nbn:se:uu:diva-17318 (URN)11198281 (PubMedID)
Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2011-01-13
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