Two independent chromosomal rearrangements, a very small (550 kb) duplication of the 7q subtelomeric region and an atypical 11q13.2 (NF1) microdeletio

Two independent chromosomal rearrangements, a very small (550 kb) duplication of the 7q subtelomeric region and an atypical 11q13.2 (NF1) microdeletion, in a girl with neurofibromatosis.
Authors:	Canals Gustavo A.; Beyer, V.; Haaf, Thomas; Zechner, U.
Language:	English
Research Context:	Case Reports
Date of Publication (YYYY-MM-DD):	2008-09-09
Title of Journal:	Cytogenetic and Genome Research
Journal Abbrev.:	Cytogenet. Genome Res.
Volume:	119
Issue / Number:	1 - 2
Start Page:	158
End Page:	64
Copyright:	Copyright © 2008
Review Status:	not specified
Audience:	Experts Only
Abstract / Description:	Most patients with neurofibromatosis (NF1) are endowed with heterozygous mutations in the NF1 gene. Approximately 5% show an interstitial deletion of chromosome 11q13.2 (including NF1) and in most cases also a more severe phenotype. Here we report on a 7-year-old girl with classical NF1 signs, and in addition mild overgrowth (97th percentile), relatively low OFC (10th-25th percentile), facial dysmorphy, hoarse voice, and developmental delay. FISH analysis revealed a 11q13.2 microdeletion as well as an unbalanced 7p;13q translocation leading to trisomy of the 7q36.3 subtelomeric region. The patient's mother and grandmother who were phenotypically normal carried the same unbalanced translocation. The 11q13.2 microdeletion had arisen de novo. Array comparative genomic hybridization (CGH) demonstrated gain of a 550-kb segment from 7qter and loss of 2.5 Mb from 11q13.2 (an atypical NF1 microdeletion). We conclude that the patient's phenotype is caused by the atypical NF1 deletion, whereas 7q36.3 trisomy represents a subtelomeric copy number variation without phenotypic consequences. To our knowledge this is the first report that a duplication of the subtelomeric region of chromosome 7q containing functional genes (FAM62B, WDR60, and VIPR2) can be tolerated without phenotypic consequences. The 11q13.2 microdeletion (containing nine more genes than the common NF1 microdeletions) and the 7qter duplication were not accompanied by unexpected clinical features. Most likely the 7qter trisomy and the 11q13.2 microdeletion coincide by chance in our patient.
Comment of the Author/Creator:	Request reprints from Dr. Canals Gustavo A.  Institut für Humangenetik, Universitätsklinikum  Langenbeckstrasse 1, DE-55101 Mainz (Germany)  telephone: +49 6131 175791; fax +49 6131 175690  e-mail: adolfocanals@educ.ar
External Publication Status:	published
Document Type:	Article
Version Comment:	Automatic journal name synchronization
Communicated by:	Hans-Hilger Ropers
Affiliations:	MPI für molekulare Genetik
External Affiliations:	a.Institute for Human Genetics, Johannes Gutenberg University, Mainz (Germany);  b.Institute of Biology and Medical Genetics, Charles University Second Medical School and University Hospital Motol, Prague (Czech Republic);  c.Institute of Medical Genetics, Charite, Humboldt University, Berlin (Germany);  eDepartment of Medical Genetics, Charles University, Prague (Czech Republic).