Interstitial microdeletions including the chromosome band 4q13.2 and the UBA6 gene as possible causes of intellectual disability and behavior disorder.
The few proximal 4q chromosomal aberrations identified in patients with neurodevelopmental phenotypes that have been published to date are variable in type, size and breakpoints and, therefore, encompass different chromosome bands and genes, making the establishment of genotype-phenotype correlations a challenging task. Here, microarray-based copy number analysis allowed us the detection of two novel and partially overlapping deletions in two unrelated families. In Family 1, a 4q13.1-q13.2 deletion of 3.84 Mb was identified in a mother with mild intellectual disability and in her two children, both with mild intellectual disability and attention deficit hyperactivity disorder. In Family 2, a de novo 4q13.2-q13.3 deletion of 6.81 Mb was detected in a female patient, born to unaffected parents, with a diagnosis of mild intellectual disability, behavioral disorder and facial dysmorphism. The shortest region of overlap between these two aberrations is located at chromosome 4q13.2 and includes 17 genes amongst of which we suggest UBA6 (ubiquitin-like modifier-activating enzyme 6) as a strong candidate gene 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-USC, CIBERER, Fundacion Publica Galega de Medicina Xenomica - SERGAS, Santiago de Compostela, Spain.
Francisco
F
Barros
Grupo de Medicina Xenomica-USC, CIBERER, Fundacion Publica Galega de Medicina Xenomica - SERGAS, Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, Spain.
Montse
M
Fernandez-Prieto
Departamento de Psicologia Clinica y Psicobiologia - Universidade de Santiago de Compostela, Grupo de Medicina Xenomica-USC, Santiago de Compostela, Spain.
Rocio
R
Martinez-Regueiro
Departamento de Pediatria, Hospital Clinico Universitario de Santiago de Compostela - Unidad de Neurologia Pediatrica, Santiago de Compostela, Spain.
Manuel
M
Castro-Gago
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-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.
Angel
A
Carracedo
Departamento de Pediatria, Hospital Clinico Universitario de Santiago de Compostela - Unidad de Neurologia Pediatrica, Santiago de Compostela, Spain.
Carmen
C
Gomez-Lado
Departamento de Pediatria, Hospital Clinico Universitario de Santiago de Compostela - Unidad de Neurologia Pediatrica, Santiago de Compostela, Spain.
Jesus
J
Eiris
D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005190:Family; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008297:Male; D001523:Mental Disorders / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics*
C521757:UBA6 protein, human; D044764:Ubiquitin-Activating Enzymes
4q13.1-q13.2 deletion; 4q13.2 deletion; 4q13.2-q13.3 deletion; EPHA5; SNP microarray; UBA6; attention deficit hyperactivity disorder; copy number variation; intellectual disability