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.
Nagamani
Sandesh Chakravarthy Sreenath
SC
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Erez
Ayelet
A
Shen
Joseph
J
Li
Chumei
C
Roeder
Elizabeth
E
Cox
Sarah
S
Karaviti
Lefkothea
L
Pearson
Margret
M
Kang
Sung-Hae L
SH
Sahoo
Trilochan
T
Lalani
Seema R
SR
Stankiewicz
Pawel
P
Sutton
V Reid
VR
Cheung
Sau Wai
SW
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