Maternally inherited duplication of chromosome 7, dup(7)(p11.2p12), associated with mild cognitive deficit without features of Silver–Russell syndrome

• Published in: American journal of medical genetics. Part A Vol. 143A; no. 13; pp. 1489 - 1493
• Main Authors: Leach, Natalia T., Chudoba, Ilse, Stewart, Tasheena V., Holmes, Lewis B., Weremowicz, Stanislawa
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2007; Wiley-Liss
• Subjects: Adult; Biological and medical sciences; Chromosomal Instability; chromosome 7; Chromosome Banding; Chromosomes, Human, Pair 7 - genetics; Cognition Disorders - diagnosis; Cognition Disorders - genetics; duplication; Dwarfism - genetics; Female; fluorescence in situ hybridization (FISH); Humans; In Situ Hybridization, Fluorescence; Male; Medical genetics; Medical sciences; multicolor banding (mBAND); Silver–Russell syndrome (SRS); Syndrome; Chromosomal aberration; Cognitive disorder; Silver-Russell syndrome (SRS); fluorescence in situ hybridization (FISH); Chromosome C7; multicolor banding (mBAND); Genetic disease; duplication; Association; chromosome 7; Fluorescence in situ hybridization; Silver-Russell syndrome; Abnormal chromosome; Chromosome duplication
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.31794

We report on a familial duplication in the short arm of chromosome 7, dup(7)(p11.2p12), present in three generations. The duplication was identified by GTG‐banding and fluorescence in situ hybridization (FISH) with a whole chromosome 7 DNA painting probe that verified that the duplicated material originated from chromosome 7. The multicolor banding (mBAND) was used to refine the breakpoint assignment. The duplication identified in the proband was also present in her son and mother. All three carriers have mild cognitive deficiencies. Interstitial duplications of the short arm of chromosome 7, although relatively uncommon, have been described in association with a variety of clinical features, including mental retardation of varying severity. Duplication of the p11.2p13 region on chromosome 7 was reported in association with Silver–Russell syndrome (SRS), and an overlapping dup(7)(p11.2p14.1)dn was described in an individual with autistic disorder. Furthermore, a potentially overlapping maternally transmitted inverted duplication, dup(7)(p13p12.2), was reported in patients with cognitive delay. These observations and the phenotype of our duplication carriers suggest that partial trisomy of the proximal 7p region causes cognitive deficiency. The maternal origin of the duplication is of special interest in light of genomic imprinting and implication of the 7p11‐p13 region in the SRS etiology. Locus‐specific FISH targeting a growth factor receptor binding protein 10 (GRB10), the strong candidate for SRS residing at 7p12.2, showed that it is not duplicated in our patients. Our study helps refine the SRS critical region on 7p and extends our understanding of the clinical manifestations associated with 7p duplications. © 2007 Wiley‐Liss, Inc.