Redefined genomic architecture in 15q24 directed by patient deletion/duplication breakpoint mapping.
We report four new patients with a submicroscopic deletion in 15q24 manifesting developmental delay, short stature, hypotonia, digital abnormalities, joint laxity, genital abnormalities, and characteristic facial features. These clinical features are shared with six recently reported patients with a 15q24 microdeletion, supporting the notion that this is a recognizable syndrome. We describe a case of an ~2.6 Mb microduplication involving a portion of the minimal deletion critical region in a 15-year-old male with short stature, mild mental retardation, attention deficit hyperactivity disorder, Asperger syndrome, decreased joint mobility, digital abnormalities, and characteristic facial features. Some of these features are shared with a recently reported case with a 15q24 microduplication involving the minimal deletion critical region. We also report two siblings and their mother with duplication adjacent and distal to this region exhibiting mild developmental delay, hypotonia, tapering fingers, characteristic facial features, and prominent ears. The deletion and duplication breakpoints were mapped by array comparative genomic hybridization and the genomic structure in 15q24 was analyzed further. Surprisingly, in addition to the previously recognized three low-copy repeat clusters (BP1, BP2, and BP3), we identified two other paralogous low-copy repeat clusters that likely mediated the formation of alternative sized 15q24 genomic rearrangements via non-allelic homologous recombination.
El-Hattab
Ayman W
AW
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Rm R809, Houston, TX 77030, USA.
Smolarek
Teresa A
TA
Walker
Martha E
ME
Schorry
Elizabeth K
EK
Immken
LaDonna L
LL
Patel
Gayle
G
Abbott
Mary-Alice
MA
Lanpher
Brendan C
BC
Ou
Zhishuo
Z
Kang
Sung-Hae L
SH
Patel
Ankita
A
Scaglia
Fernando
F
Lupski
James R
JR
Cheung
Sau Wai
SW
Stankiewicz
Pawel
P
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D010641:Phenotype