Female patient with autistic disorder, intellectual disability, and co-morbid anxiety disorder: Expanding the phenotype associated with the recurrent 3q13.2-q13.31 microdeletion.
In recent years, the advent of comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays and its use as a first genetic test for the diagnosis of patients with neurodevelopmental phenotypes has allowed the identification of novel submicroscopic chromosomal abnormalities (namely, copy number variants or CNVs), imperceptible by conventional cytogenetic techniques. The 3q13.31 microdeletion syndrome (OMIM #615433) has been defined as a genomic disorder mainly characterized by developmental delay, postnatal overgrowth, hypotonia, genital abnormalities in males, and characteristic craniofacial features. Although the 3q13.31 CNVs are variable in size, a 3.4 Mb recurrently altered region at 3q13.2-q13.31 has been recently described and non-allelic homologous recombination (NAHR) mediated by flanking human endogenous retrovirus (HERV-H) elements has been suggested as the mechanism of deletion formation. We expand the phenotypic spectrum associated with this recurrent deletion performing the clinical description of a 9-year-old female patient with autistic disorder, total absence of language, intellectual disability, anxiety disorder and disruptive, and compulsive eating behaviors. The array-based molecular karyotyping allowed the identification of a de novo recurrent 3q13.2-q13.31 deletion encompassing 25 genes. In addition, we compare her clinical phenotype with previous reports of patients with neurodevelopmental and behavioral disorders and proximal 3q microdeletions. Finally, we also review the candidate genes proposed so far for these phenotypes.
Grupo de Medicina Xenomica, Universidade de Santiago de Compostela, Centro Nacional de Genotipado-Plataforma de Recursos Biomoleculares y Bioinformaticos-Instituto de Salud Carlos III (CeGen-PRB2-ISCIII), Santiago de Compostela, Spain.
Ines
I
Quintela
Grupo de Medicina Xenomica, CIBERER, Fundacion Publica Galega de Medicina Xenomica-SERGAS, Santiago de Compostela, Spain.
Lorena
L
Gomez-Guerrero
Grupo de Medicina Xenomica, CIBERER, Fundacion Publica Galega de Medicina Xenomica-SERGAS, Santiago de Compostela, Spain.
Montse
M
Fernandez-Prieto
Departamento de Psicologia Evolutiva y de la Educacion, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Mariela
M
Resches
Grupo de Medicina Xenomica, CIBERER, Fundacion Publica Galega de Medicina Xenomica-SERGAS, Santiago de Compostela, Spain.
Francisco
F
Barros
Grupo de Medicina Xenomica, Universidade de Santiago de Compostela, Centro Nacional de Genotipado-Plataforma de Recursos Biomoleculares y Bioinformaticos-Instituto de Salud Carlos III (CeGen-PRB2-ISCIII), Santiago de Compostela, Spain.|Grupo de Medicina Xenomica, 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.
Angel
A
Carracedo
D000328:Adult; D001008:Anxiety Disorders / Q000235:genetics* / Q000473:pathology; D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology; D002648:Child; D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D015897:Comorbidity; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008297:Male; D010641:Phenotype; D011379:Prognosis; D013577:Syndrome
3q13.2-q13.31 microdeletion; 3q13.31 microdeletion; SNP array; anxiety disorder; autistic disorder; intellectual disability