A de novo microdeletion in NRXN1 in a Dutch patient with mild intellectual disability, microcephaly and gonadal dysgenesis

Agha Z, Iqbal Z, Kleefstra T, Zweier C, Pfundt R, Qamar R, Van Bokhoven H, Willemsen MH (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Genetics Research Cambridge University Press (CUP)

Book Volume: 97

Pages Range: e19

DOI: 10.1017/S001667231500021X

Abstract

This report is regarding a Dutch female with microcephaly, mild intellectual disability (ID), gonadal dysgenesis and dysmorphic facial features with synophrys. Upon genotyping, an ~455 kb de novo deletion encompassing the first exon of NRXN1 was found. Bidirectional sequencing of the coding exons of the NRXN1 alpha isoform was subsequently performed to investigate the possibility of a pathogenic mutation on the other allele, but we could not find any other mutation. Previously, many heterozygous mutations as well as microdeletions in NRXN1 were shown to be associated with ID, autism, schizophrenia, and other psychiatric and psychotic disorders. Our results are in agreement with other reports that show that NRXN1 deletions can lead to ID, microcephaly and mild dysmorphic features. However, this is the first report of gonadal dysgenesis being associated with such deletions. It is not clear whether there is a causal relationship between the NRXN1 deletion and gonadal dysgenesis, but it is of interest that the FSHR gene, which encodes the follicle-stimulating hormone receptor causative correlation that is mutated in ovarian dysgenesis, is located proximal to the NRXN1 gene. Given that most of the females carrying NRXN1 deletions have been diagnosed at a prepubertal age, gynecologic screening of female carriers of a NRXN1 deletion is warranted.

Authors with CRIS profile

Christiane Zweier Medizinische Fakultät

Additional Organisation(s)

Institute of Human Genetics

Involved external institutions

COMSATS Institute of Information Technology Abbottabad PK Pakistan (PK) Radboud University Nijmegen NL Netherlands (NL) COMSATS Institute of Information Technology PK Pakistan (PK)

How to cite

APA:

Agha, Z., Iqbal, Z., Kleefstra, T., Zweier, C., Pfundt, R., Qamar, R.,... Willemsen, M.H. (2015). A de novo microdeletion in NRXN1 in a Dutch patient with mild intellectual disability, microcephaly and gonadal dysgenesis. Genetics Research, 97, e19. https://doi.org/10.1017/S001667231500021X

MLA:

Agha, Zehra, et al. "A de novo microdeletion in NRXN1 in a Dutch patient with mild intellectual disability, microcephaly and gonadal dysgenesis." Genetics Research 97 (2015): e19.

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