title: Compound heterozygous deletion of NRXN1 causing severe developmental delay with early onset epilepsy in two sisters.
abstract: Neurexin 1 (NRXN1) is a cell adhesion protein, the normal function of which is critical for effective neurotransmission. It forms a trans-synaptic complex in the central nervous system with neuroligin. There has been one case in the literature of a patient with a heterozygous deletion in NRXN1 on one allele and a nonsense mutation on the other allele, reported to have a Pitt Hopkins-like phenotype. We report on two daughters of healthy, nonconsanguineous, Caucasian parents with biallelic NRXN1 deletions identified by array CGH. The children presented with severe early onset epilepsy, profound developmental delay, gastroesophageal reflux disease, constipation, and early onset puberty. Our report confirms that biallelic NRXN1 mutations result in a severe recessive mental retardation syndrome and broadens the range of phenotypes associated with this gene.
authors.affiliation: Department of Clinical Genetics, Churchill Hospital, Oxford, UK. victoria.harrison@orh.nhs.uk
authors.forename: Victoria
authors.initials: V
authors.lastname: Harrison
authors.forename: Lyndsey
authors.initials: L
authors.lastname: Connell
authors.forename: Jesse
authors.initials: J
authors.lastname: Hayesmoore
authors.forename: Joanna
authors.initials: J
authors.lastname: McParland
authors.forename: Michael G
authors.initials: MG
authors.lastname: Pike
authors.forename: Edward
authors.initials: E
authors.lastname: Blair
mesh_terms: D000293:Adolescent; D000483:Alleles; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002648:Child; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D003248:Constipation / Q000235:genetics / Q000473:pathology; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology; D004827:Epilepsy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000235:genetics / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007223:Infant; D040582:Inheritance Patterns; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D011629:Puberty, Precocious / Q000235:genetics / Q000473:pathology; D017384:Sequence Deletion; D035781:Siblings
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules