Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions

Christian P. Schaaf, Philip M. Boone, Srirangan Sampath, Charles Williams, Patricia I. Bader, Jennifer M. Mueller, Oleg A. Shchelochkov, Chester W. Brown, Heather P. Crawford, James A. Phalen, Nicole R. Tartaglia, Patricia Evans, William M. Campbell, Anne Chun-Hui Tsai, Lea Parsley, Stephanie W. Grayson, Angela Scheuerle, Carol D. Luzzi, Sandra K. Thomas, Patricia A. Eng & 4 others Sung Hae L Kang, Ankita Patel, Pawel Stankiewicz, Sau W. Cheung

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Copy number variants (CNVs) and intragenic rearrangements of the NRXN1 (neurexin 1) gene are associated with a wide spectrum of developmental and neuropsychiatric disorders, including intellectual disability, speech delay, autism spectrum disorders (ASDs), hypotonia and schizophrenia. We performed a detailed clinical and molecular characterization of 24 patients who underwent clinical microarray analysis and had intragenic deletions of NRXN1. Seventeen of these deletions involved exons of NRXN1, whereas seven deleted intronic sequences only. The patients with exonic deletions manifested developmental delay/intellectual disability (93%), infantile hypotonia (59%) and ASDs (56%). Congenital malformations and dysmorphic features appeared infrequently and inconsistently among this population of patients with NRXN1 deletions. The more C-terminal deletions, including those affecting the β isoform of neurexin 1, manifested increased head size and a high frequency of seizure disorder (88%) when compared with N-terminal deletions of NRXN1.

Original languageEnglish (US)
Pages (from-to)1240-1247
Number of pages8
JournalEuropean Journal of Human Genetics
Volume20
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

Genetic Association Studies
Exons
Muscle Hypotonia
Intellectual Disability
Language Development Disorders
Microarray Analysis
Epilepsy
Schizophrenia
Protein Isoforms
Head
Population
Genes
Autism Spectrum Disorder

Keywords

  • epilepsy
  • genotype-phenotype correlation
  • intellectual disability
  • macrocephaly
  • neurexin 1

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Schaaf, C. P., Boone, P. M., Sampath, S., Williams, C., Bader, P. I., Mueller, J. M., ... Cheung, S. W. (2012). Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions. European Journal of Human Genetics, 20(12), 1240-1247. https://doi.org/10.1038/ejhg.2012.95

Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions. / Schaaf, Christian P.; Boone, Philip M.; Sampath, Srirangan; Williams, Charles; Bader, Patricia I.; Mueller, Jennifer M.; Shchelochkov, Oleg A.; Brown, Chester W.; Crawford, Heather P.; Phalen, James A.; Tartaglia, Nicole R.; Evans, Patricia; Campbell, William M.; Chun-Hui Tsai, Anne; Parsley, Lea; Grayson, Stephanie W.; Scheuerle, Angela; Luzzi, Carol D.; Thomas, Sandra K.; Eng, Patricia A.; Kang, Sung Hae L; Patel, Ankita; Stankiewicz, Pawel; Cheung, Sau W.

In: European Journal of Human Genetics, Vol. 20, No. 12, 12.2012, p. 1240-1247.

Research output: Contribution to journalArticle

Schaaf, CP, Boone, PM, Sampath, S, Williams, C, Bader, PI, Mueller, JM, Shchelochkov, OA, Brown, CW, Crawford, HP, Phalen, JA, Tartaglia, NR, Evans, P, Campbell, WM, Chun-Hui Tsai, A, Parsley, L, Grayson, SW, Scheuerle, A, Luzzi, CD, Thomas, SK, Eng, PA, Kang, SHL, Patel, A, Stankiewicz, P & Cheung, SW 2012, 'Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions', European Journal of Human Genetics, vol. 20, no. 12, pp. 1240-1247. https://doi.org/10.1038/ejhg.2012.95
Schaaf CP, Boone PM, Sampath S, Williams C, Bader PI, Mueller JM et al. Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions. European Journal of Human Genetics. 2012 Dec;20(12):1240-1247. https://doi.org/10.1038/ejhg.2012.95
Schaaf, Christian P. ; Boone, Philip M. ; Sampath, Srirangan ; Williams, Charles ; Bader, Patricia I. ; Mueller, Jennifer M. ; Shchelochkov, Oleg A. ; Brown, Chester W. ; Crawford, Heather P. ; Phalen, James A. ; Tartaglia, Nicole R. ; Evans, Patricia ; Campbell, William M. ; Chun-Hui Tsai, Anne ; Parsley, Lea ; Grayson, Stephanie W. ; Scheuerle, Angela ; Luzzi, Carol D. ; Thomas, Sandra K. ; Eng, Patricia A. ; Kang, Sung Hae L ; Patel, Ankita ; Stankiewicz, Pawel ; Cheung, Sau W. / Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions. In: European Journal of Human Genetics. 2012 ; Vol. 20, No. 12. pp. 1240-1247.
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