TY - JOUR
T1 - Y chromosome gene copy number and lack of autism phenotype in a male with an isodicentric Y chromosome and absent NLGN4Y expression
AU - Ross, Judith L.
AU - Bloy, Luke
AU - Roberts, Timothy P.L.
AU - Miller, Judith
AU - Xing, Chao
AU - Silverman, Lawrence A.
AU - Zinn, Andrew R.
N1 - Funding Information:
We thank the participating subjects and their families. We thank Karen Kowal for excellent assistance with the study. This work was supported in part by Department of Defense Idea Research Grant Proposal # AR140197 (JR, TR, LB), R21 MH109158-01 (JR, TR, LB), and NIH U54HD086984 (TR).
Funding Information:
Department of Defense Idea Research Grant Proposal, Grant/Award Number: AR140197; National Institute of Neurological Disorders and Stroke, Grant/Award Number: MH109158-01; National Institute of Health, Grant/Award Number: NIH U54HD086984
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - We describe a unique male with a dicentric Y chromosome whose phenotype was compared to that of males with 47,XYY (XYY). The male Y-chromosome aneuploidy XYY is associated with physical, behavioral/cognitive phenotypes, and autism spectrum disorders. We hypothesize that increased risk for these phenotypes is caused by increased copy number/overexpression of Y-encoded genes. Specifically, an extra copy of the neuroligin gene NLGN4Y might elevate the risk of autism in boys with XYY. We present a unique male with the karyotype 46,X,idic(Y)(q11.22), which includes duplication of the Y short arm and proximal long arm and deletion of the distal long arm, evaluated his physical, behavioral/cognitive, and neuroimaging/magnetoencephalography (MEG) phenotypes, and measured blood RNA expression of Y genes. The proband had tall stature and cognitive function within the typical range, without autism features. His blood RNA showed twofold increase in expression of Yp genes versus XY controls, and absent expression of deleted Yq genes, including NLGN4Y. The M100 latencies were similar to findings in typically developing males. In summary, the proband had overexpression of a subset of Yp genes, absent NLGN4Y expression, without ASD findings or XYY-MEG latency findings. These results are consistent with a role for NLGN4Y overexpression in the etiology of behavioral phenotypes associated with XYY. Further investigation of NLGN4Y as an ASD risk gene in XYY is warranted. The genotype and phenotype(s) of this subject may also provide insight into how Y chromosome genes contribute to normal male development and the male predominance in ASD.
AB - We describe a unique male with a dicentric Y chromosome whose phenotype was compared to that of males with 47,XYY (XYY). The male Y-chromosome aneuploidy XYY is associated with physical, behavioral/cognitive phenotypes, and autism spectrum disorders. We hypothesize that increased risk for these phenotypes is caused by increased copy number/overexpression of Y-encoded genes. Specifically, an extra copy of the neuroligin gene NLGN4Y might elevate the risk of autism in boys with XYY. We present a unique male with the karyotype 46,X,idic(Y)(q11.22), which includes duplication of the Y short arm and proximal long arm and deletion of the distal long arm, evaluated his physical, behavioral/cognitive, and neuroimaging/magnetoencephalography (MEG) phenotypes, and measured blood RNA expression of Y genes. The proband had tall stature and cognitive function within the typical range, without autism features. His blood RNA showed twofold increase in expression of Yp genes versus XY controls, and absent expression of deleted Yq genes, including NLGN4Y. The M100 latencies were similar to findings in typically developing males. In summary, the proband had overexpression of a subset of Yp genes, absent NLGN4Y expression, without ASD findings or XYY-MEG latency findings. These results are consistent with a role for NLGN4Y overexpression in the etiology of behavioral phenotypes associated with XYY. Further investigation of NLGN4Y as an ASD risk gene in XYY is warranted. The genotype and phenotype(s) of this subject may also provide insight into how Y chromosome genes contribute to normal male development and the male predominance in ASD.
KW - NLGN4Y
KW - RNA expression
KW - XYY
KW - Y chromosome
KW - autism spectrum disorder
KW - neuroligin4Y
UR - http://www.scopus.com/inward/record.url?scp=85066990855&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066990855&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.32745
DO - 10.1002/ajmg.b.32745
M3 - Article
C2 - 31161682
AN - SCOPUS:85066990855
SN - 1552-4841
VL - 180
SP - 471
EP - 482
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 7
ER -