TY - JOUR
T1 - Redefined genomic architecture in 15q24 directed by patient deletion/ duplication breakpoint mapping
AU - El-Hattab, Ayman W.
AU - Ou, Zhishuo
AU - Kang, Sung Hae L.
AU - Patel, Ankita
AU - Scaglia, Fernando
AU - Lupski, James R.
AU - Cheung, Sau Wai
AU - Stankiewicz, Pawel
AU - Smolarek, Teresa A.
AU - Walker, Martha E.
AU - Schorry, Elizabeth K.
AU - Immken, La Donna L.
AU - Patel, Gayle
AU - Abbott, Mary Alice
AU - Lanpher, Brendan C.
N1 - Funding Information:
Acknowledgments We would like to thank our patients and their families. P.S. was supported in part by Grant R13-0005-04/2008 from the Polish Ministry of Science and Higher Education.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1007/s00439-009-0706-x
DO - 10.1007/s00439-009-0706-x
M3 - Article
C2 - 19557438
AN - SCOPUS:70350179748
SN - 0340-6717
VL - 126
SP - 589
EP - 602
JO - Human genetics
JF - Human genetics
IS - 4
ER -