title: Microdeletion of 12q24.31: report of a girl with intellectual disability, stereotypies, seizures and facial dysmorphisms.
abstract: We provide a detailed clinical and molecular characterization of an 11-year-old female patient presenting with neurodevelopmental delay (NDD), intellectual disability (ID), seizures, stereotypies and dysmorphic features. Chromosomal microarrays analysis (CMA) detected a small, rare de novo deletion on chromosome 12q24.31 encompassing 31 protein-coding RefSeq genes and a microRNA. Phenotypic comparison with molecularly well-defined cases previously reported in the literature harboring an overlapping 12q24.31 microdeletion indicate that these patients shared common clinical features including neurodevelopmental delay, intellectual disability and behavioral problems. Also, seizures and dysmorphic features are frequent and a consistent pattern was recognized. Since there are remarkable resemblance between the patient described here and at least another one previously reported, our report is provides supportive evidence for the existence of an emerging syndrome caused by a microdeletion in 12q24.31. We propose a minimal region shared among patients contributing to the etiology of the common clinical features observed suggesting as candidate, for the first time, the gene SETD1B which is a component of a histone methyltransferase complex. In addition, we speculate on the possible contributive role of the MIR4304 to some clinical features observed in our patient. Evaluation of more patients with well-characterized deletions within 12q24.31, as well as careful clinical assessment of them, is needed to corroborate our hypothesis, to perform a more detailed genotype-phenotype correlation and, finally, to fully delineate this emerging microdeletion syndrome.
authors.affiliation: Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Palumbo
authors.forename: Pietro
authors.initials: P
authors.lastname: Palumbo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Delvecchio
authors.forename: Teresa
authors.initials: T
authors.lastname: Palladino
authors.forename: Raffaella
authors.initials: R
authors.lastname: Stallone
authors.forename: Matteo
authors.initials: M
authors.lastname: Crisetti
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
mesh_terms: D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005147:Facial Bones / Q000002:abnormalities*; D019066:Facies; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D012640:Seizures / Q000175:diagnosis / Q000235:genetics*; D013239:Stereotyped Behavior
keywords: 12q24.31 microdeletion; chromosomal microarrays analysis; genotype-phenotype correlation