A 6Mb deletion in band 2q22 due to a complex chromosome rearrangement associated with severe psychomotor retardation, microcephaly and distinctive dysmorphic facial features.
High-resolution analyses of complex chromosome rearrangements (CCR) have demonstrated in individuals with abnormal phenotypes that not all seemingly balanced CCRs based on G-banding are completely balanced at breakpoint level. Here we report on an apparently balanced de novo CCR involving chromosomes 2, 3 and 5 present in a 6-month-old girl. She was referred for genetic evaluation because of severe psychomotor retardation, distinctive dysmorphic features and microcephaly. A 1Mb resolution array-CGH analysis of DNA from the patient revealed a deletion of about 6Mb for chromosome 2. FISH analysis showed that the deletion interval found in band 2q22 mapped at the translocation breakpoint, and that the ZFHX1B gene, which is known to be involved in the Mowat-Wilson syndrome, is located within the deletion interval. To our knowledge this is the first case of a complex chromosomal rearrangement associated with Mowat-Wilson syndrome. Our data illustrate the important role for high-resolution investigation of apparently balanced chromosome rearrangements in patients with unexplained psychomotor retardation and/or other clinical features, and should contribute to our understanding of the mechanisms involved in chromosome rearrangement.
Hoffer
M J V
MJ
Center of Human and Clinical Genetics, Department of Clinical Genetics, Leiden University Medical Center, Gebouw 2 S-6-P, Einthovenweg 20, NL-2333 ZC Leiden, The Netherlands. m.j.v.hoffer@lumc.nl
Hilhorst-Hofstee
Y
Y
Knijnenburg
J
J
Hansson
K-B
KB
Engelberts
A C
AC
Laan
L A E M
LA
Bakker
E
E
Rosenberg
C
C
D019457:Chromosome Breakage; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D004247:DNA / Q000235:genetics; D005145:Face / Q000002:abnormalities*; D005260:Female; D017353:Gene Deletion; D015321:Gene Rearrangement; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology; D021141:Nucleic Acid Amplification Techniques; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000235:genetics; D014178:Translocation, Genetic; D000074165:Zinc Finger E-box Binding Homeobox 2
D018398:Homeodomain Proteins; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D004247:DNA