Clinical spectrum associated with recurrent genomic rearrangements in chromosome 17q12.
Deletions in chromosome 17q12 encompassing the HNF1 beta gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. Earlier reports of patients with this microdeletion syndrome have suggested an absence of cognitive impairment, differentiating it from most other contiguous gene deletion syndromes. The reciprocal duplication of 17q12 is rare and has been hypothesized to be associated with an increased risk of epilepsy and mental retardation. We conducted a detailed clinical and molecular characterization of four patients with a deletion and five patients with a reciprocal duplication of this region. Our patients with deletion of 17q12 presented with cognitive impairment, cystic renal disease, seizures, and structural abnormalities of the brain. Patients with reciprocal duplications manifest with cognitive impairment and behavioral abnormalities, but not with seizures. Our findings expand the phenotypic spectrum associated with rearrangements of 17q12 and show that cognitive impairment is a part of the phenotype of individuals with deletions of 17q12.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Sandesh Chakravarthy Sreenath
SC
Nagamani
Ayelet
A
Erez
Joseph
J
Shen
Chumei
C
Li
Elizabeth
E
Roeder
Sarah
S
Cox
Lefkothea
L
Karaviti
Margret
M
Pearson
Sung-Hae L
SH
Kang
Trilochan
T
Sahoo
Seema R
SR
Lalani
Pawel
P
Stankiewicz
V Reid
VR
Sutton
Sau Wai
SW
Cheung
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D005260:Female; D020440:Gene Duplication; D015321:Gene Rearrangement / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D010641:Phenotype; D011247:Pregnancy; D012008:Recurrence; D055815:Young Adult
C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta