ABSTRACT
Introduction: The pure interstitial trisomy 11q11q23.2 is an uncommon genomic disorder associated with nonrecurrent intrachromosomal duplications. The phenotype is characterized by intellectual disability and craniofacial abnormalities. Given their uncommonness, a comprehensive genotype-phenotype correlation has not fully been defined. Case Presentation: We report the clinical and cytogenomic characterization of a 5-year-old boy with intellectual disability, psychomotor retardation, craniofacial dysmorphism, genital anomalies, and pure interstitial trisomy 11q arising from a nonrecurrent 11q13.1q22.3 intrachromosomal duplication in a high-mosaic state (>80%). The duplicated chromosome was characterized by cytogenetics, multicolor banding FISH, and SNP array. We demonstrated the wide mosaic distribution of the 11q duplication by interphase FISH in tissues from different embryonic germ layers. The duplication involves a copy number gain of 45.3 Mb containing 22 dosage-sensitive genes. We confirmed the overexpression of dosage-sensitive genes along the duplicated region using RT-qPCR. Discussion: Only 8 patients have been described. Our patient shares clinical features with previous reports but differs from them by the presence of genital anomalies. We provide a detailed clinical review and an accurate genotype-phenotype correlation and propose PC, NDUFV1, FGF3, FGF4, and DHCR7 as dosage-sensitive genes with a possible role in the clinical spectrum of our patient; however, expression changes of FGF3/4 were not detected since they must be regulated in a spatiotemporal way. This patient contributes to the accurate description of the pure interstitial trisomy 11q. Future reports could continue to delineate the description, considering the relationship between the chromosome segment and the genes involved.
ABSTRACT
BACKGROUND: The 15q11q13 region is subject to imprinting and is involved in various structural rearrangements. Less than 1% of Angelman Syndrome patients are due to translocations involving 15q11q13. These translocations can arise de novo or result from the segregation of chromosomes involved in a familial balanced translocation. RESULTS: A 5-year-old Mexican girl presented with developmental delay, minor dysmorphic features and history of exotropia. G-banding chromosome analysis established the diagnosis of Angelman Syndrome resulting from a familial translocation t(10;15) involving the 15q11.2 region. The available family members were studied using banding and molecular cytogenetic techniques, including Microarray-based Comparative Genomic Hybridization, which revealed additional unexpected results: a coincidental and smaller 15q deletion, asymptomatic duplications in 15q11.2 and Xp22.31 regions. CONCLUSIONS: This report demonstrates the usefulness of array CGH for a detailed characterization of familial translocations, including the detection of submicroscopic copy number variations, which would otherwise be missed by karyotype analysis alone. Our report also expands two molecularly characterized rare patient cohorts: Angelman Syndrome patients due to familial translocations and patients with 15q11.2 duplications of paternal origin.
ABSTRACT
The absence of an appropriate central tolerance in primary immunodeficiencies favors proliferation of autoreactive lymphocyte clones, causing a greater incidence of autoimmunity. Del 22q11.2 syndrome presents an increased incidence of allergic and autoimmune diseases. One of the most relevant and frequent immune manifestations is autoimmune thrombocytopenia. We present the case of a pediatric patient with autoimmune thrombocytopenia due to the immunological dysregulation observed in partial DiGeorge syndrome.
