title: A maternally inherited 16p13.11-p12.3 duplication concomitant with a de novo SOX5 deletion in a male patient with global developmental delay, disruptive and obsessive behaviors and minor dysmorphic features.
abstract: We detail here the clinical description and the family genetic study of a male patient with global developmental delay, disruptive and obsessive behaviors and minor dysmorphic features and a combination of two rare genetic variants: a maternally inherited 16p13.11-p12.3 duplication and a de novo 12p12.1 deletion affecting SOX5. The 16p13.11 microduplication has been implicated in several neurodevelopmental and behavioral disorders and is characterized by variable expressivity and incomplete penetrance. The causes of this variation in phenotypic expression are not fully clear, representing a challenge in genetic diagnosis and counseling. However, several authors have proposed the two-hit model as one of the underlying mechanisms for this phenotypic heterogeneity. Our data could also support this two-hit model in which the 16p13.11-p12.3 duplication might contribute to the phenotype, not only as a single event but also in association with the SOX5 deletion. The SOX5 gene plays important roles in various developmental processes and has been associated with several neurodevelopmental disorders, mainly intellectual disability, developmental delay and language and/or speech delay as well as with behavior problems and dysmorphic features. However, many of the physical features and behavioral manifestations as well as language deficiencies present in our patient are consistent with those previously reported for SOX5 deletions. Patients carrying multiple genomic variants, as the one presented here, illustrate the difficulty in analyzing genotypes when the contribution of each variant results in overlapping phenotypes and/or, alternatively, in the modification of the clinical manifestations defined by the coexisting variant.
authors.affiliation: Grupo de Medicina Xenomica - Universidad de Santiago de Compostela, Centro Nacional de Genotipado - Instituto Carlos III, Santiago de Compostela, Spain.
authors.forename: Ines
authors.initials: I
authors.lastname: Quintela
authors.affiliation: Grupo de Medicina Xenomica - USC, CIBERER, Fundacion Publica Galega de Medicina Xenomica - SERGAS, Santiago de Compostela, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Barros
authors.affiliation: Grupo de Medicina Xenomica - USC, Fundacion Publica Galega de Medicina Xenomica - SERGAS, Santiago de Compostela, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Lago-Leston
authors.affiliation: Departamento de Pediatria, Hospital Clinico Universitario de Santiago de Compostela - Unidad de Neurologia Pediatrica, Santiago de Compostela, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Castro-Gago
authors.affiliation: Grupo de Medicina Xenomica - Universidad de Santiago de Compostela, Centro Nacional de Genotipado - Instituto Carlos III, Santiago de Compostela, Spain.|Grupo de Medicina Xenomica - USC, CIBERER, Fundacion Publica Galega de Medicina Xenomica - SERGAS, Santiago de Compostela, Spain.|Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.affiliation: Departamento de Pediatria, Hospital Clinico Universitario de Santiago de Compostela - Unidad de Neurologia Pediatrica, Santiago de Compostela, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Eiris
mesh_terms: D002648:Child; D058674:Chromosome Duplication; D002885:Chromosomes, Human, Pair 16; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019066:Facies; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007805:Language Development Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008957:Models, Genetic; D009770:Obsessive Behavior / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D055755:SOXD Transcription Factors / Q000235:genetics*
chemical_list: C490301:SOX5 protein, human; D055755:SOXD Transcription Factors
keywords: 12p12.1 deletion; 16p13.11-p12.3 duplication; SOX5; disruptive behavior; dysmorphism; global developmental delay; intellectual disability; obsessive behavior