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Interstitial deletions of the long arm of chromosome 12 are rare and only few cases have been reported in literature so far, with different phenotypic features related to size and gene content of deleted regions. Five patients reported a 12q15-q21 deletion, sharing a 1.3 Mb small region of overlap (SRO) and presenting with developmental delay, nasal speech and mild dysmorphic features. We identified by microarray analysis a new case of 12q15 deletion. Our patient clinical features allow the refinement of the SRO to CNOT2 , KCNMB4 , and PTPRB genes, improving genotype-phenotype correlations. [ABSTRACT FROM AUTHOR]

Abstract: Background and objectives: Submicroscopic chromosomal rearrangements are the most common identifiable causes of intellectual disability and autism spectrum disorders associated with dysmorphic features. Chromosomal microarray (CMA) can detect copy number variants <1 Mb and identifies size and presence of known genes. The aim of this study was to demonstrate the usefulness of CMA, as a first-tier tool in detecting the etiology of unexplained intellectual disability/autism spectrum disorders (ID/ASDs) associated with dysmorphic features in a large cohort of pediatric patients. Patients and methods: We studied 349 individuals; 223 males, 126 females, aged 5 months-19 years. Blood samples were analyzed with CMA at a resolution ranging from 1 Mb to 40 Kb. The imbalance was confirmed by FISH or qPCR. We considered copy number variants (CNVs) causative if the variant was responsible for a known syndrome, encompassed gene/s of known function, occurred de novo or, if inherited, the parent was variably affected, and/or the involved gene/s had been reported in association with ID/ASDs in dedicated databases. Results: 91 CNVs were detected in 77 (22.06%) patients: 5 (6.49%) of those presenting with borderline cognitive impairment, 54 (70.13%) with a variable degree of DD/ID, and 18/77 (23.38%) with ID of variable degree and ASDs. 16/77 (20.8%) patients had two different rearrangements. Deletions exceeded duplications (58 versus 33); 45.05% (41/91) of the detected CNVs were de novo, 45.05% (41/91) inherited, and 9.9% (9/91) unknown. The CNVs caused the phenotype in 57/77 (74%) patients; 12/57 (21.05%) had ASDs/ID, and 45/57 (78.95%) had DD/ID. Conclusions: Our study provides further evidence of the high diagnostic yield of CMA for genetic testing in children with unexplained ID/ASDs who had dysmorphic features. We confirm the value of CMA as the first-tier tool in the assessment of those conditions in the pediatric setting. [Copyright &y& Elsevier]

In recent years, there has been an explosive increase in genetic studies related to autism spectrum disorder (ASD). This implicated the accumulation of a large amount of molecular data that may be used to verify various hypotheses and models developed to explore the complex genetic component of ASD. Several lines of evidence support the view that structural genomic variation contributes to the pathogenesis of ASD. The introduction of more sophisticated techniques for whole-genome screening, including array comparative genome hybridization and high-resolution single nucleotide polymorphism analysis, has allowed to identify an increasing number of ASD susceptibility loci. Copy number variants (CNVs) are the most common type of structural variation in the human genome and are considered important contributors to the pathogenesis of neurodevelopmental disorders, including ASD. In this review, we describe the accumulated evidence concerning the genetic events associated with ASD, and summarize current knowledge about the clinical relevance of CNVs in these disorders. • Specific genetic etiology of ASD is identifiable in 5-15% of individuals. • Copy number variants have important role in ASD pathogenesis. • Copy number variants frequency ranges from 8 to 21% in individuals with ASD. [ABSTRACT FROM AUTHOR]

Abstract: Turner syndrome is a condition caused by numeric and structural abnormalities of the X chromosome, and is characterized by a series of clinical features, the most common being short stature and gonadal dysgenesis. An increased frequency of autoimmune diseases as well as an elevated incidence of autoantibodies has been observed in Turner patients. We present a unique case of mosaic Turner syndrome with a complex rearrangement consisting of a partial deletion of chromosome 2q and duplication of chromosome 10p {[46],XX,der(2)t(2;10)(2pter→2q37::10p13→10pter)[127]/45,X,der(2)t(2;10)(2pter→2q37::10p13→10pter)[23]}. The patient is affected by partial empty sella, in association with a group of multiorgan autoimmunity-related manifestations including Hashimoto''s thyroiditis, celiac disease, insulin-dependent diabetes mellitus (Type 1 diabetes, T1D), possible autoimmune inner ear disease with sensorineural deficit, preclinical Addison disease and alopecia universalis. The patient was previously described at the age of 2.4years and now re-evaluated at the age of 14years after she developed autoimmune conditions. AIRE gene screening revealed heterozygous c.834 C>G polymorphism (p.Ser278Arg) and IVS9+6G>A variation, thus likely excluding autoimmune polyendocrine syndrome Type 1 (APECED). Heterozygous R620W polymorphism of the protein tyrosine phosphatase non receptor type 22 (PTPN22) gene was detected in patient''s DNA. SNP-array analysis revealed that autoimmunity-related genes could be affected by the partial monosomy 2q and trisomy 10p. These data suggest that early genetic analysis in TS patients with complex associations of multiorgan autoimmune manifestations would permit a precise diagnostic classification and also be an indicator for undiscovered pathogenetic mechanisms. [Copyright &y& Elsevier]