Expanding the clinical phenotype at the 3q13.31 locus with a new case of microdeletion and first characterization of the reciprocal duplication.
Congenital deletions at the 3q13.31 locus have been recently described as a novel microdeletion syndrome characterized by developmental delay, postnatal overgrowth, hypoplastic male genitalia and characteristic facial features. A common critical region of overlapping of 580kb was delineated including two strong candidate genes for developmental delay: DRD3 and ZBTB20. In this report, we describe a new case of 3q13.31 microdeletion identified by array-CGH in a 16year-old girl sharing clinical features commonly observed in the 3q13.31 microdeletion syndrome. This girl had a microdeletion of 7.39Mb spanning the common critical region of overlapping. More interestingly, we report for the first time the existence of a microduplication reciprocal to the microdeletion syndrome. This familial 2.76Mb microduplication identified by array-CGH was carried by two brothers and their father. The phenotype shared by the brothers resembled the phenotype related to the 3q13.31 microdeletion syndrome including especially severe intellectual disability, developmental delay, behavioral abnormalities and obesity. This microduplication involves three strong candidate genes for the developmental delay ZBTB20, LSAMP and GAP43. Further molecular characterization showed that DRD3, another strong candidate gene for developmental delay, was not included in the duplicated region. However, a dosage alteration of this gene cannot be completely excluded as the duplication was inverted at proximity of this gene, as revealed by FISH analysis. Finally, we hypothesized that the phenotype shared by the two brothers could be related to a gene dosage imbalance even if gene expression could not be measured in relevant tissues such as brain or adipocytes.
CHU Bordeaux, Service de Génétique Médicale, Place Amélie Raba Léon, Bordeaux, France. marie-laure.vuillaume@chu-bordeaux.fr
Marie-Laure
ML
Vuillaume
Marie-Ange
MA
Delrue
Sophie
S
Naudion
Jérôme
J
Toutain
Patricia
P
Fergelot
Benoit
B
Arveiler
Didier
D
Lacombe
Caroline
C
Rooryck
D000293:Adolescent; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics; D017353:Gene Deletion; D018628:Gene Dosage; D020131:Genes, Duplicate; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D050637:Receptors, Dopamine D3 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D015816:Cell Adhesion Molecules, Neuronal; C493593:DRD3 protein, human; D019922:GAP-43 Protein; D058851:GPI-Linked Proteins; D009419:Nerve Tissue Proteins; D050637:Receptors, Dopamine D3; D014157:Transcription Factors; C427486:ZBTB20 protein, human; C095362:limbic system-associated membrane protein
3q13.31; Array-CGH; Developmental delay; Microdeletion; Microduplication; Obesity