Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities.
Chromosome region 1q21.1 contains extensive and complex low-copy repeats, and copy number variants (CNVs) in this region have recently been reported in association with congenital heart defects, developmental delay, schizophrenia and related psychoses. We describe 21 probands with the 1q21.1 microdeletion and 15 probands with the 1q21.1 microduplication. These CNVs were inherited in most of the cases in which parental studies were available. Consistent and statistically significant features of microcephaly and macrocephaly were found in individuals with microdeletion and microduplication, respectively. Notably, a paralog of the HYDIN gene located on 16q22.2 and implicated in autosomal recessive hydrocephalus was inserted into the 1q21.1 region during the evolution of Homo sapiens; we found this locus to be deleted or duplicated in the individuals we studied, making it a probable candidate for the head size abnormalities observed. We propose that recurrent reciprocal microdeletions and microduplications within 1q21.1 represent previously unknown genomic disorders characterized by abnormal head size along with a spectrum of developmental delay, neuropsychiatric abnormalities, dysmorphic features and congenital anomalies. These phenotypes are subject to incomplete penetrance and variable expressivity.
Brunetti-Pierri
Nicola
N
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Berg
Jonathan S
JS
Scaglia
Fernando
F
Belmont
John
J
Bacino
Carlos A
CA
Sahoo
Trilochan
T
Lalani
Seema R
SR
Graham
Brett
B
Lee
Brendan
B
Shinawi
Marwan
M
Shen
Joseph
J
Kang
Sung-Hae L
SH
Pursley
Amber
A
Lotze
Timothy
T
Kennedy
Gail
G
Lansky-Shafer
Susan
S
Weaver
Christine
C
Roeder
Elizabeth R
ER
Grebe
Theresa A
TA
Arnold
Georgianne L
GL
Hutchison
Terry
T
Reimschisel
Tyler
T
Amato
Stephen
S
Geragthy
Michael T
MT
Innis
Jeffrey W
JW
Obersztyn
Ewa
E
Nowakowska
Beata
B
Rosengren
Sally S
SS
Bader
Patricia I
PI
Grange
Dorothy K
DK
Naqvi
Sayed
S
Garnica
Adolfo D
AD
Bernes
Saunder M
SM
Fong
Chin-To
CT
Summers
Anne
A
Walters
W David
WD
Lupski
James R
JR
Stankiewicz
Pawel
P
Cheung
Sau Wai
SW
Patel
Ankita
A
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics; D055815:Young Adult