Twelve new patients with 13q deletion syndrome: genotype-phenotype analyses in progress.
13q deletion is characterized by a wide phenotypic spectrum resulting from a partial deletion of the long arm of chromosome 13. The main clinical features are mental retardation, growth retardation, craniofacial dysmorphy and various congenital defects. Only one recent Italian study was aimed at determining genotype-phenotype correlations among 13q deletions from a group of mainly live born children, using array-CGH and FISH. In order to improve the molecular characterization of 13q monosomy, 12 new patients (9 foetuses and 3 children) were collected based on a cohort of holoprosencephaly (HPE) linked to ZIC2 gene deletion and/or patients with 13q deletion diagnosed by standard karyotype. First, quantitative gene screening using MLPA (Multiplex Ligation dependent Probe Amplification) was performed to look for ZIC2 gene deletion and then, CGH array analysis was carried out using the Agilent Human Genome CGH microarray 4x44K (Agilent Technologies, Santa Clara, USA). All the foetuses had severe cerebral midline malformations associated with a deletion including the ZIC2 gene. We report one patient with Steinfeld phenotype linked to this chromosomal anomaly, and suggest that some of the associations between cerebral midline malformation and limb defects might be related to 13q deletion. Further candidate genes are suspected to explain the malformations associated with cerebral anomalies in the hypothesis of a contiguous gene syndrome: SPRY2 in 13q31.1 is implicated in lens cell proliferation and differentiation for congenital cataract; GPC5 in 13q32 is mainly expressed in the mesenchyme of the developing limb bud for upper limb anomalies.
Quélin
Chloé
C
Service de Génétique Médicale, CHU Hôpital Sud, Rennes Cedex 2, France.
Bendavid
Claude
C
Dubourg
Christèle
C
de la Rochebrochard
Céline
C
Lucas
Josette
J
Henry
Catherine
C
Jaillard
Sylvie
S
Loget
Philippe
P
Loeuillet
Laurence
L
Lacombe
Didier
D
Rival
Jean-Marie
JM
David
Véronique
V
Odent
Sylvie
S
Pasquier
Laurent
L
D000015:Abnormalities, Multiple / Q000235:genetics*; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D005260:Female; D005333:Fetus; D005838:Genotype; D053673:Glypicans / Q000235:genetics; D006130:Growth Disorders / Q000235:genetics; D016142:Holoprosencephaly; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D012886:Skull / Q000002:abnormalities; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics
C106228:GPC5 protein, human; D053673:Glypicans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C485561:SPRY2 protein, human; D014157:Transcription Factors; C491812:ZIC2 protein, human