Phenotype and 244k array-CGH characterization of chromosome 13q deletions: an update of the phenotypic map of 13q21.1-qter.
Partial deletions of the long arm of chromosome 13 lead to variable phenotypes dependant on the size and position of the deleted region. In order to update the phenotypic map of chromosome 13q21.1-qter deletions, we applied 244k Agilent oligonucleotide-based array-CGH to determine the exact breakpoints in 14 patients with partial deletions of this region. Subsequently, we linked the genotype to the patient's phenotype. Using this approach, we were able to refine the smallest deletion region linked to short stature (13q31.3: 89.5-91.6 Mb), microcephaly (13q33.3-q34), cortical development malformations (13q33.1-qter), Dandy-Walker malformation (DWM) (13q32.2-q33.1), corpus callosum agenesis (CCA) (13q32.3-q33.1), meningocele/encephalocele (13q31.3-qter), DWM, CCA, and neural tube defects (NTDs) taken together (13q32.3-q33.1), ano-/microphthalmia (13q31.3-13qter), cleft lip/palate (13q31.3-13q33.1), lung hypoplasia (13q31.3-13q33.1), and thumb a-/hypoplasia (13q31.3-q33.1 and 13q33.3-q34). Based on observations of this study and previous reports we suggest a new entity, "distal limb anomalies association," linked to 13q31.3q33.1 segment. Most of the individuals with deletion of any part of 13q21qter showed surprisingly similar facial dysmorphic features, and thus, a "13q deletion facial appearance" was suggested. Prominent nasal columella was mapped between 13q31.3 and 13q33.3, and micrognathia between 13q21.33 and 13q31.1. The degree of mental delay did not display a particular phenotype-genotype correlation on chromosome 13. In contrast to previous reports of carriers of 13q32 band deletions as the most seriously affected patients, we present two such individuals with long-term survival, 28 and 2.5 years.
Department of Clinical Genetics, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
Maria
M
Kirchhoff
Anne-Marie
AM
Bisgaard
Radka
R
Stoeva
Boyan
B
Dimitrov
Gabriele
G
Gillessen-Kaesbach
Jean-Pierre
JP
Fryns
Hanne
H
Rose
Liliana
L
Grozdanova
Ivan
I
Ivanov
Kathelijn
K
Keymolen
Christina
C
Fagerberg
Lisbeth
L
Tranebjaerg
Flemming
F
Skovby
Margarita
M
Stefanova
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D000013:Congenital Abnormalities / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D055815:Young Adult