Ade novomicrodeletion inNRXN1in a Dutch patient with mild intellectual disability, microcephaly and gonadal dysgenesis

• DOI: 10.1017/s001667231500021x
• Publication Date: 2015-10-06T08:38:32Z
• Authors: ZEHRA AGHA; ZAFAR IQBAL; TJITSKE KLEEFSTRA; CHRISTIANE ZWEIER; ROLPH PFUNDT; RAHEEL QAMAR; HANS VAN BOKHOVEN; MARJOLEIN H. WILL...
• Keywords: Adult; 0301 basic medicine; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience; Cell Adhesion Molecules, Neuronal; Calcium-Binding Proteins; Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health Sciences; Nerve Tissue Proteins; Gonadal Dysgenesis; 3. Good health; 03 medical and health sciences; Chromosomes, Human, Pair 2; Intellectual Disability; Microcephaly; Humans; Receptors, FSH; Abnormalities, Multiple; Female; Chromosome Deletion; Neural Cell Adhesion Molecules; Gene Deletion; Netherlands

SummaryThis report is regarding a Dutch female with microcephaly, mild intellectual disability (ID), gonadal dysgenesis and dysmorphic facial features with synophrys. Upon genotyping, an ~455 kbde novodeletion encompassing the first exon ofNRXN1was found. Bidirectional sequencing of the coding exons of theNRXN1alpha 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 inNRXN1were shown to be associated with ID, autism, schizophrenia, and other psychiatric and psychotic disorders. Our results are in agreement with other reports that show thatNRXN1deletions 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 theNRXN1deletion and gonadal dysgenesis, but it is of interest that theFSHRgene, which encodes the follicle-stimulating hormone receptor causative correlation that is mutated in ovarian dysgenesis, is located proximal to theNRXN1gene. Given that most of the females carryingNRXN1deletions have been diagnosed at a prepubertal age, gynecologic screening of female carriers of aNRXN1deletion is warranted.