TY - JOUR
T1 - Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions
AU - Schaaf, Christian P.
AU - Boone, Philip M.
AU - Sampath, Srirangan
AU - Williams, Charles
AU - Bader, Patricia I.
AU - Mueller, Jennifer M.
AU - Shchelochkov, Oleg A.
AU - Brown, Chester W.
AU - Crawford, Heather P.
AU - Phalen, James A.
AU - Tartaglia, Nicole R.
AU - Evans, Patricia
AU - Campbell, William M.
AU - Chun-Hui Tsai, Anne
AU - Parsley, Lea
AU - Grayson, Stephanie W.
AU - Scheuerle, Angela
AU - Luzzi, Carol D.
AU - Thomas, Sandra K.
AU - Eng, Patricia A.
AU - Kang, Sung Hae L
AU - Patel, Ankita
AU - Stankiewicz, Pawel
AU - Cheung, Sau W.
N1 - Funding Information:
We are indebted to the patients and families who participated in this study. We thank John W Belmont for contributing a patient to this study, and for helpful discussions. Dr Schaaf’s work is generously supported by the Joan and Stanford Alexander family.
PY - 2012/12
Y1 - 2012/12
N2 - 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.
AB - 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.
KW - epilepsy
KW - genotype-phenotype correlation
KW - intellectual disability
KW - macrocephaly
KW - neurexin 1
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U2 - 10.1038/ejhg.2012.95
DO - 10.1038/ejhg.2012.95
M3 - Article
C2 - 22617343
AN - SCOPUS:84869235517
SN - 1018-4813
VL - 20
SP - 1240
EP - 1247
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 12
ER -