TY - JOUR
T1 - Mutations in NRXN1 in a family multiply affected with brain disorders
T2 - NRXN1 mutations and brain disorders
AU - Duong, Linh
AU - Klitten, Laura L
AU - Møller, Rikke S
AU - Ingason, Andrés
AU - Jakobsen, Klaus D
AU - Skjødt, Celina
AU - Didriksen, Michael
AU - Hjalgrim, Helle
AU - Werge, Thomas
AU - Tommerup, Niels
N1 - Copyright © 2012 Wiley Periodicals, Inc.
PY - 2012/4
Y1 - 2012/4
N2 - Mutation of the neurexin1-gene, NRXN1, interrupting the expression of neurexin1 has been associated with schizophrenia, autism, and intellectual disability. We have identified a family multiply affected with psychiatric, neurological, and somatic disorders along with an intricate co-segregation of NRXN1 mutations. The proband suffered from autism, mental retardation, and epilepsy and on genotyping it was revealed that he carried a compound heterozygous mutation in the NRXN1 consisting of a 451¿kb deletion, affecting the promoter and first introns in addition to a point mutation, predicted to be deleterious to NRXN1. The deletion was passed on from the patient's mother who was clinically characterized by sub-diagnostic autistic traits in addition to type 1 diabetes mellitus. The point mutation was subsequently found in the patient's brother, suffering from a psychotic disorder, which implies that the point mutation was inherited from the deceased father, who was diagnosed with schizophrenia. The observations suggest a possible gene-dose effect of NRXN1 mutations on type and severity of mental illness and support the notion that the penetrance and pleiotropy of pathogenic CNVs in general are determined by additional genetic variants in the genome. Finally the findings also propose a linkage of NRXN1 neurobiology to epilepsy and possibly to type 1 diabetes.
AB - Mutation of the neurexin1-gene, NRXN1, interrupting the expression of neurexin1 has been associated with schizophrenia, autism, and intellectual disability. We have identified a family multiply affected with psychiatric, neurological, and somatic disorders along with an intricate co-segregation of NRXN1 mutations. The proband suffered from autism, mental retardation, and epilepsy and on genotyping it was revealed that he carried a compound heterozygous mutation in the NRXN1 consisting of a 451¿kb deletion, affecting the promoter and first introns in addition to a point mutation, predicted to be deleterious to NRXN1. The deletion was passed on from the patient's mother who was clinically characterized by sub-diagnostic autistic traits in addition to type 1 diabetes mellitus. The point mutation was subsequently found in the patient's brother, suffering from a psychotic disorder, which implies that the point mutation was inherited from the deceased father, who was diagnosed with schizophrenia. The observations suggest a possible gene-dose effect of NRXN1 mutations on type and severity of mental illness and support the notion that the penetrance and pleiotropy of pathogenic CNVs in general are determined by additional genetic variants in the genome. Finally the findings also propose a linkage of NRXN1 neurobiology to epilepsy and possibly to type 1 diabetes.
U2 - 10.1002/ajmg.b.32036
DO - 10.1002/ajmg.b.32036
M3 - Journal article
C2 - 22337556
SN - 1552-485X
VL - 159B
SP - 354
EP - 358
JO - American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
JF - American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
IS - 3
ER -
