Smith-Magenis syndrome resulting from a de novo direct insertion of proximal 17q into 17p11.2

• Published in: American journal of medical genetics 1998-04, Vol.77 (1), p.23-27
• Main Authors: Park, Jonathan P., Moeschler, John B., Davies, Wendy S., Patel, Pragna I., Mohandas, T.K.
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - genetics; Autistic Disorder - genetics; Biological and medical sciences; Child; Chromosome Mapping; Chromosomes, Human, Pair 17 - genetics; Complex syndromes; Humans; In Situ Hybridization, Fluorescence; intrachromosomal insertion; Karyotyping; Male; Medical genetics; Medical sciences; microdeletion syndrome; Smith-Magenis syndrome; Syndrome; Translocation, Genetic
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/(SICI)1096-8628(19980428)77:1<23::AID-AJMG6>3.0.CO;2-M

We report on a de novo intrachromosomal rearrangement of chromosome 17 in a patient with Smith‐Magenis syndrome (SMS). This 11‐year‐old boy had short stature, mid‐facial hypoplasia, and behavioral problems characteristic of this syndrome. Cytogenetic analysis showed that the proximal long arm of a chromosome 17 (q11.2‐q21.3) was inserted into its short arm at p11.2, resulting in an apparent deletion of the SMS critical region [ins(17)(p11.2q11.2q21.3)]. Fluorescence in situ hybridization studies (FISH) demonstrated that the inserted segment included both the ERBB2 and RARA loci, and dual color hybridizations defined the insertion as direct, with ERBB2 located more proximally on the short arm of the der(17). The resulting deletion of the short arm included loci c130G3, D17S258, FLI, and D17S29, while the more proximal loci, D17S446 and D17S58, remained apparently unaffected and in their native locations. The CMT1A locus also remained in its native location on the short arm of the metacentric der(17) chromosome. A de novo intrachromosomal insertional rearrangement of chromosome 17 in a case of SMS has not been reported previously and further illustrates the instability of this chromosomal region. Am. J. Med. Genet. 77:23–27, 1998. © 1998 Wiley‐Liss, Inc.