TY - JOUR
T1 - Recurrent duplications of 17q12 associated with variable phenotypes
AU - Mitchell, Elyse
AU - Douglas, Andrew
AU - Kjaegaard, Susanne
AU - Callewaert, Bert
AU - Vanlander, Arnaud
AU - Janssens, Sandra
AU - Yuen, Amy Lawson
AU - Skinner, Cindy
AU - Failla, Pinella
AU - Alberti, Antonino
AU - Avola, Emanuela
AU - Fichera, Marco
AU - Kibaek, Maria
AU - Digilio, Maria C.
AU - Hannibal, Mark C.
AU - den Hollander, Nicolette S.
AU - Bizzarri, Veronica
AU - Renieri, Alessandra
AU - Mencarelli, Maria Antonietta
AU - Fitzgerald, Tomas
AU - Piazzolla, Serena
AU - van Oudenhove, Elke
AU - Romano, Corrado
AU - Schwartz, Charles
AU - Eichler, Evan E.
AU - Slavotinek, Anne
AU - Escobar, Luis
AU - Rajan, Diana
AU - Crolla, John
AU - Carter, Nigel
AU - Hodge, Jennelle C.
AU - Mefford, Heather C.
N1 - Publisher Copyright:
© 2015 Wiley Periodicals, Inc.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - The ability to identify the clinical nature of the recurrent duplication of chromosome 17q12 has been limited by its rarity and the diverse range of phenotypes associated with this genomic change. In order to further define the clinical features of affected patients, detailed clinical information was collected in the largest series to date (30 patients and 2 of their siblings) through a multi-institutional collaborative effort. The majority of patients presented with developmental delays varying from mild to severe. Though dysmorphic features were commonly reported, patients do not have consistent and recognizable features. Cardiac, ophthalmologic, growth, behavioral, and other abnormalities were each present in a subset of patients. The newly associated features potentially resulting from 17q12 duplication include height and weight above the 95th percentile, cataracts, microphthalmia, coloboma, astigmatism, tracheomalacia, cutaneous mosaicism, pectus excavatum, scoliosis, hypermobility, hypospadias, diverticulum of Kommerell, pyloric stenosis, and pseudohypoparathryoidism. The majority of duplications were inherited with some carrier parents reporting learning disabilities or microcephaly. We identified additional, potentially contributory copy number changes in a subset of patients, including one patient each with 16p11.2 deletion and 15q13.3 deletion. Our data further define and expand the clinical spectrum associated with duplications of 17q12 and provide support for the role of genomic modifiers contributing to phenotypic variability.
AB - The ability to identify the clinical nature of the recurrent duplication of chromosome 17q12 has been limited by its rarity and the diverse range of phenotypes associated with this genomic change. In order to further define the clinical features of affected patients, detailed clinical information was collected in the largest series to date (30 patients and 2 of their siblings) through a multi-institutional collaborative effort. The majority of patients presented with developmental delays varying from mild to severe. Though dysmorphic features were commonly reported, patients do not have consistent and recognizable features. Cardiac, ophthalmologic, growth, behavioral, and other abnormalities were each present in a subset of patients. The newly associated features potentially resulting from 17q12 duplication include height and weight above the 95th percentile, cataracts, microphthalmia, coloboma, astigmatism, tracheomalacia, cutaneous mosaicism, pectus excavatum, scoliosis, hypermobility, hypospadias, diverticulum of Kommerell, pyloric stenosis, and pseudohypoparathryoidism. The majority of duplications were inherited with some carrier parents reporting learning disabilities or microcephaly. We identified additional, potentially contributory copy number changes in a subset of patients, including one patient each with 16p11.2 deletion and 15q13.3 deletion. Our data further define and expand the clinical spectrum associated with duplications of 17q12 and provide support for the role of genomic modifiers contributing to phenotypic variability.
KW - CNV
KW - Duplication
KW - Genotype phenotype
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U2 - 10.1002/ajmg.a.37351
DO - 10.1002/ajmg.a.37351
M3 - Article
AN - SCOPUS:84959361371
SN - 1552-4825
VL - 167
SP - 3038
EP - 3045
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 12
ER -