CoChat
Sign Up
Cited by 121Genetics and Neurodevelopmental DisordersGenomic variations and chromosomal abnormalitiesGenomics and Rare Diseases

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.

Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1

Open access
Gregor, Anne, Albrecht, Beate, Bader, Ingrid, Bijlsma, Emilia K, Ekici, Arif B, Engels, Hartmut, Hackmann, Karl, Horn, Denise, Hoyer, Juliane, Klapecki, Jakub, Kohlhase, Jürgen, Maystadt, Isabelle, Nagl, Sandra, Prott, Eva, Tinschert, Sigrid, Ullmann, Reinhard, Wohlleber, Eva, Woods, Geoffrey, Reis, André, Rauch, Anita, Zweier, Christiane·2011·BMC Medical Genetics
DOI 10.1186/1471-2350-12-106PMC PMC3162517
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Heterozygous copy-number and missense variants in CNTNAP2 and NRXN1 have repeatedly been associated with a wide spectrum of neuropsychiatric disorders such as developmental language and autism spectrum disorders, epilepsy and schizophrenia. Recently, homozygous or compound heterozygous defects in either gene were reported as causative for severe intellectual disability. Methods: 99 patients with severe intellectual disability and resemblance to Pitt-Hopkins syndrome and/or suspected recessive inheritance were screened for mutations in CNTNAP2 and NRXN1. Molecular karyotyping was performed in 45 patients. In 8 further patients with variable intellectual disability and heterozygous deletions in either CNTNAP2 or NRXN1, the remaining allele was sequenced. Results: By molecular karyotyping and mutational screening of CNTNAP2 and NRXN1 in a group of severely intellectually disabled patients we identified a heterozygous deletion in NRXN1 in one patient and heterozygous splice-site, frameshift and stop mutations in CNTNAP2 in four patients, respectively. Neither in these patients nor in eight further patients with heterozygous deletions within NRXN1 or CNTNAP2 we could identify a defect on the second allele. One deletion in NRXN1 and one deletion in CNTNAP2 occurred de novo, in another family the deletion was also identified in the mother who had learning difficulties, and in all other tested families one parent was shown to be healthy carrier of the respective deletion or mutation. Conclusions: We report on patients with heterozygous defects in CNTNAP2 or NRXN1 associated with severe intellectual disability, which has only been reported for recessive defects before. These results expand the spectrum of phenotypic severity in patients with heterozygous defects in either gene. The large variability between severely affected patients and mildly affected or asymptomatic carrier parents might suggest the presence of a second hit, not necessarily located in the same gene.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/1471-2350-12-106

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Schematic drawing of NRXN1 with localization of novel and published mutations and deletions. Schematic drawing of genomic structure of alpha 1 isoform of NRXN1 showing domain-coding exons and localization of mutations and deletions. Deletions found in our study are represented by black bars. Published biallelic aberrations are shown with black dotted lines, whereas heterozygous losses and gains are marked by grey solid and dashed lines, respectively. Abbreviations are as follows: SP, signal peptide; LamG, laminin-G domain; EGF, epidermal growth factor like domain; TM, transmembrane region; PDZBD, PDZ-domain binding site.
Figure 1 Schematic drawing of NRXN1 with localization of novel and published mutations and deletions. Schematic drawing of genomic structure of alpha 1 isoform of NRXN1 showing domain-coding exons and localization of mutations and deletions. Deletions found in our study are represented by black bars. Published biallelic aberrations are shown with black dotted lines, whereas heterozygous losses and gains are marked by grey solid and dashed lines, respectively. Abbreviations are as follows: SP, signal peptide; LamG, laminin-G domain; EGF, epidermal growth factor like domain; TM, transmembrane region; PDZBD, PDZ-domain binding site.CC BY · PubMed Central
Figure 2 Schematic drawing of CNTNAP2 with localization of novel and published mutations and deletions. Schematic drawing of genomic structure of CNTNAP2 showing domain-coding exons and localization of mutations and deletions. Mutations and deletions found in our study are represented by black arrows and bars. Published biallelic aberrations are shown with black dotted lines, whereas heterozygous defects are shown in grey. Abbreviations are as follows: SP, signal peptide; DISC, discoidin-like domain; LamG, laminin-G domain; EGF, epidermal growth factor like domain; FIB, fibrinogen-like domain; TM, transmembrane region; PDZBD, PDZ-domain binding site.
Figure 2 Schematic drawing of CNTNAP2 with localization of novel and published mutations and deletions. Schematic drawing of genomic structure of CNTNAP2 showing domain-coding exons and localization of mutations and deletions. Mutations and deletions found in our study are represented by black arrows and bars. Published biallelic aberrations are shown with black dotted lines, whereas heterozygous defects are shown in grey. Abbreviations are as follows: SP, signal peptide; DISC, discoidin-like domain; LamG, laminin-G domain; EGF, epidermal growth factor like domain; FIB, fibrinogen-like domain; TM, transmembrane region; PDZBD, PDZ-domain binding site.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 33 references

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Gregor, A., Albrecht, B., Bader, I., Bijlsma, E. K., Ekici, A. B., Engels, H., Hackmann, K., Horn, D., Hoyer, J., Klapecki, J., Kohlhase, J., Maystadt, I., Nagl, S., Prott, E., Tinschert, S., Ullmann, R., Wohlleber, E., Woods, G., Reis, A., Rauch, A., & Zweier, C.
Affiliations
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • University of Duisburg-Essen (DE)
  • Leiden University (NL)
  • University of Bonn (DE)
  • Technische Universität Dresden (DE)
  • Charité – Universitätsmedizin Berlin (DE)
  • Instytut Matki i Dziecka (PL)
  • Institute of Pathology and Genetics (BE)
  • Max Planck Institute for Molecular Genetics (DE)
  • Addenbrooke's Hospital (GB)
  • University of Zurich (CH)
Corresponding author
Zweier, Christiane
ORCID
Venue
BMC Medical Genetics
Publisher
Springer Science and Business Media LLC
Published
2011-08-09
Volume
12
Issue
1
Pages
106-106
ISSN
1471-2350 (ISSN-L)
DOI
10.1186/1471-2350-12-106
PMC
PMC3162517
OpenAlex
W2121619206
Cited by
121
References
33
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 12 · 2017: 5 · 2016: 9 · 2015: 11 · 2014: 15 · 2013: 20 · 2012: 12
FWCI
9.38
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Medical Genetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • DuEPublico (University of Duisburg-Essen) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • OPUS FAU (Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV), on behalf of the Universitätsbibliothek Erlangen-Nürnberg) (submittedVersion, other-oa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • Deutsche Forschungsgemeinschaft
  • Bundesministerium für Bildung und Forschung
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
CNTNAP2, NRXN1, severe intellectual disability, heterozygous deletion, recessive inheritance, Pitt-Hopkins syndrome, splice site mutation, frameshift mutation, de novo mutations, second hit, carrier parents, phenotypic variability, neuropsychiatric disorders
MeSH terms
Adolescent, Alleles, Calcium-Binding Proteins, Child, Child Development Disorders, Pervasive, Child, Preschool, Female, Heterozygote, Humans, Hyperventilation, Karyotyping, Male, Membrane Proteins, Intellectual Disability, Nerve Tissue Proteins, Cell Adhesion Molecules, Neuronal, Frameshift Mutation, Gene Deletion, Codon, Terminator, Neural Cell Adhesion Molecules, Facies, RNA Splice Sites, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review