A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures.
We report a recurrent microdeletion syndrome causing mental retardation, epilepsy and variable facial and digital dysmorphisms. We describe nine affected individuals, including six probands: two with de novo deletions, two who inherited the deletion from an affected parent and two with unknown inheritance. The proximal breakpoint of the largest deletion is contiguous with breakpoint 3 (BP3) of the Prader-Willi and Angelman syndrome region, extending 3.95 Mb distally to BP5. A smaller 1.5-Mb deletion has a proximal breakpoint within the larger deletion (BP4) and shares the same distal BP5. This recurrent 1.5-Mb deletion contains six genes, including a candidate gene for epilepsy (CHRNA7) that is probably responsible for the observed seizure phenotype. The BP4-BP5 region undergoes frequent inversion, suggesting a possible link between this inversion polymorphism and recurrent deletion. The frequency of these microdeletions in mental retardation cases is approximately 0.3% (6/2,082 tested), a prevalence comparable to that of Williams, Angelman and Prader-Willi syndromes.
Sharp
Andrew J
AJ
Department of Genome Sciences, University of Washington School of Medicine, 1705 NE Pacific St., Seattle, Washington 98195, USA.
Mefford
Heather C
HC
Li
Kelly
K
Baker
Carl
C
Skinner
Cindy
C
Stevenson
Roger E
RE
Schroer
Richard J
RJ
Novara
Francesca
F
De Gregori
Manuela
M
Ciccone
Roberto
R
Broomer
Adam
A
Casuga
Iris
I
Wang
Yu
Y
Xiao
Chunlin
C
Barbacioru
Catalin
C
Gimelli
Giorgio
G
Bernardina
Bernardo Dalla
BD
Torniero
Claudia
C
Giorda
Roberto
R
Regan
Regina
R
Murday
Victoria
V
Mansour
Sahar
S
Fichera
Marco
M
Castiglia
Lucia
L
Failla
Pinella
P
Ventura
Mario
M
Jiang
Zhaoshi
Z
Cooper
Gregory M
GM
Knight
Samantha J L
SJ
Romano
Corrado
C
Zuffardi
Orsetta
O
Chen
Caifu
C
Schwartz
Charles E
CE
Eichler
Evan E
EE
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002884:Chromosomes, Human, Pair 15; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D040582:Inheritance Patterns; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010375:Pedigree; D011978:Receptors, Nicotinic / Q000235:genetics; D012640:Seizures / Q000235:genetics*; D013577:Syndrome; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor