Abstract
Duplications of chromosome 8p lead to rare genetic conditions characterized by variable phenotypes. 8p21 and 8p23 duplications were associated with mental retardation but only 8p23 duplication was associated with heart defects. 8p22→ p21.3 duplications were associated with an autism spectrum disorder in several cases. We present a rare case with a de novo duplication of the entire 8p21.3→ p23.3 region, documented by karyotype, FISH, and array CGH, with t(4;8)(q35;p21.3) translocation in a 7 years-old girl. She was referred for genetic counseling at the age of 20 months due to mild dysmorphic facial features, psychomotor retardation, and a noncyanotic heart defect. Another examination carried out at the age of 5 years, enabled the diagnosis of autism spectrum disorder and attention deficit hyperactivity disorder. Upon re-examination after two years she was diagnosed with autism spectrum disorder, attention deficit hyperactivity disorder, liminal intellect with cognitive disharmony, delay in psychomotor acquisitions, developmental language delay, an instrumental disorder, and motor coordination disorder. Cytogenetic analysis using GTG technique revealed the following karyotype: 46,XX,der(4),t(4;8)(q35;p21.3). The translocation of the duplicated 8pter region to the telomeric region 4q was confirmed by FISH analysis (DJ580L5 probe). Array CGH showed: arr[GRCh37]8p23.3p21.3(125733_22400607) × 3. It identified a terminal duplication, a 22.3 Mb copy number gain of chromosome 8p23.3–p21.3, between 125,733 and 22,400,607. In this case, there is a de novo duplication of a large chromosomal segment, which was translocated to chromosome 4q. Our report provides additional data regarding neuropsychiatric features in chromosome 8p duplication. The phenotypic consequences in our patient allow clinical-cytogenetic correlations and may also reveal candidate genes for the phenotypic features.
Highlights
Significance of segmental duplications leading to abnormal gene dosage and to different disorders has been intensively studied in recent years [1].Duplications of the short arm of chromosome 8 are structural chromosomal abnormalities that lead to rare genetic conditions characterized by a variable phenotype
We present a de novo duplication of the entire region 8p21.3→ p23.3, documented by karyotype, Fluorescence in situ Hybridization (FISH), and array CGH, with translocation t(4;8)(q35;p21.3) in a 7 years-old girl with liminal intellect with cognitive disharmony, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and cardiac defects
At the age of 6 years and 11 months, she was evaluated by the pediatric neuropsychiatrist, her diagnosis being ASD, ADHD, delay in psychomotor acquisitions with mild delay in the expressive language acquisition with polymorphic dyslalia, motor coordination disorder and instrumental disorders, liminal intellect with cognitive disharmony (IQ = 83 WISC; Wechsler Intelligence Scale for Children), minimal brain lesions indices, organic brain background
Summary
Significance of segmental duplications leading to abnormal gene dosage and to different disorders has been intensively studied in recent years [1]. Duplications of the short arm of chromosome 8 are structural chromosomal abnormalities that lead to rare genetic conditions characterized by a variable phenotype. The duplicated material from 8p may remain on the same chromosome or, rarer, can be translocated to a different chromosome. It seems that the phenotypic effects are not influenced by the position of the duplicated part [4, 5]. Some chromosome 8p duplications may be familial, but an appreciable number of cases result from de novo mutations [6,7,8,9]. Inverted duplications adjacent to terminal deletions of chromosome 8p are the most common, cases with direct duplications have been described [10, 11]
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