Phenotypic Variability Associated with a Large Recurrent 1q21.1 Microduplication in a Three-Generation Family.
Recurrent copy number variants of the q21.1 region of chromosome 1 have been associated with variable clinical features, including developmental delay, mild to moderate intellectual disability, psychiatric and behavioral problems, congenital heart malformations, and craniofacial abnormalities. A subset of individuals is clinically unaffected. We describe a unique 3-generation family with a large recurrent 1q21.1 microduplication (BP2-BP4). Our observations underline the incomplete penetrance and phenotypic variability of this rearrangement. We also confirm the association with congenital heart malformations, chronic depression, and anxiety. Furthermore, we report a broader range of dysmorphic features. The extreme phenotypic heterogeneity observed in this family suggests that additional factors modify the clinical phenotype.
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Judith M A
JM
Verhagen
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Nicole
N
de Leeuw
Department of Obstetrics and Gynecology, Amphia Hospital, Breda, The Netherlands.
Dimitri N M
DN
Papatsonis
Department of Obstetrics and Gynecology, Amphia Hospital, Breda, The Netherlands.
Els W M
EW
Grijseels
Department of Pathology, Reinier de Graaf Gasthuis, Delft, The Netherlands.
Ronald R
RR
de Krijger
Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Marja W
MW
Wessels
1q21.1 microduplication; Congenital heart defects; Copy number variation; GJA5