Academic Journals Database
Disseminating quality controlled scientific knowledge

Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1

ADD TO MY LIST
 
Author(s): Gregor Anne | Albrecht Beate | Bader Ingrid | Bijlsma Emilia | Ekici Arif | 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

Journal: BMC Medical Genetics
ISSN 1471-2350

Volume: 12;
Issue: 1;
Start page: 106;
Date: 2011;
Original page

ABSTRACT
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.

Tango Jona
Tangokurs Rapperswil-Jona

     Save time & money - Smart Internet Solutions