A previously unrecognized microdeletion syndrome on chromosome 22 band q11.2 encompassing the BCR gene

TY - JOUR

T1 - A previously unrecognized microdeletion syndrome on chromosome 22 band q11.2 encompassing the BCR gene

AU - Mikhail, Fady M

AU - Descartes, Maria

AU - Piotrowski, Arkadiusz

AU - Andersson, Robin

AU - Diaz de Ståhl, Teresita

AU - Komorowski, Jan

AU - Bruder, Carl E G

AU - Dumanski, Jan P

AU - Carroll, Andrew J

N1 - (c) 2007 Wiley-Liss, Inc.

PY - 2007/9/15

Y1 - 2007/9/15

N2 - Susceptibility of the chromosome 22q11.2 region to rearrangements has been recognized on the basis of common clinical disorders such as the DiGeorge/velocardiofacial syndrome (DG/VCFs). Recent evidence has implicated low-copy repeats (LCRs); also known as segmental duplications; on 22q as mediators of nonallelic homologous recombination (NAHR) that result in rearrangements of 22q11.2. It has been shown that both deletion and duplication events can occur as a result of NAHR caused by unequal crossover of LCRs. Here we report on the clinical, cytogenetic and array CGH studies of a 15-year-old Hispanic boy with history of learning and behavior problems. We suggest that he represents a previously unrecognized microdeletion syndrome on chromosome 22 band q11.2 just telomeric to the DG/VCFs typically deleted region and encompassing the BCR gene. Using a 32K BAC array CGH chip we were able to refine and precisely narrow the breakpoints of this microdeletion, which was estimated to be 1.55-1.92 Mb in size and to span approximately 20 genes. This microdeletion region is flanked by LCR clusters containing several modules with a very high degree of sequence homology (>95%), and therefore could play a causal role in its origin.

AB - Susceptibility of the chromosome 22q11.2 region to rearrangements has been recognized on the basis of common clinical disorders such as the DiGeorge/velocardiofacial syndrome (DG/VCFs). Recent evidence has implicated low-copy repeats (LCRs); also known as segmental duplications; on 22q as mediators of nonallelic homologous recombination (NAHR) that result in rearrangements of 22q11.2. It has been shown that both deletion and duplication events can occur as a result of NAHR caused by unequal crossover of LCRs. Here we report on the clinical, cytogenetic and array CGH studies of a 15-year-old Hispanic boy with history of learning and behavior problems. We suggest that he represents a previously unrecognized microdeletion syndrome on chromosome 22 band q11.2 just telomeric to the DG/VCFs typically deleted region and encompassing the BCR gene. Using a 32K BAC array CGH chip we were able to refine and precisely narrow the breakpoints of this microdeletion, which was estimated to be 1.55-1.92 Mb in size and to span approximately 20 genes. This microdeletion region is flanked by LCR clusters containing several modules with a very high degree of sequence homology (>95%), and therefore could play a causal role in its origin.

KW - Abnormalities, Multiple

KW - Adolescent

KW - Chromosome Banding

KW - Chromosomes, Artificial, Bacterial

KW - Chromosomes, Human, Pair 22

KW - Gene Deletion

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Karyotyping

KW - Male

KW - Proto-Oncogene Proteins c-bcr

KW - Syndrome

U2 - 10.1002/ajmg.a.31882

DO - 10.1002/ajmg.a.31882

M3 - Journal article

C2 - 17676630

SN - 1552-4825

VL - 143A

SP - 2178

EP - 2184

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

IS - 18

ER -