Subject(s)
Abnormalities, Multiple/etiology , Blepharophimosis/etiology , Blepharoptosis/etiology , Chromosomes, Human, X/genetics , Genetic Diseases, X-Linked/etiology , Heart Defects, Congenital/etiology , Intellectual Disability/etiology , Mediator Complex/genetics , Mutation , Abnormalities, Multiple/pathology , Blepharophimosis/pathology , Blepharoptosis/pathology , Child, Preschool , Female , Genetic Diseases, X-Linked/pathology , Heart Defects, Congenital/pathology , Humans , Intellectual Disability/pathology , PrognosisABSTRACT
BACKGROUND: Heterozygous mutations in CTCF have been reported in patients with distinct clinical features including intellectual disability. However, the precise pathomechanism underlying the phenotype remains to be uncovered, partly because of the diverse function of CTCF. Here we describe extensive clinical and genetic investigation for two patients with a microdeletion encompassing CTCF. METHODS: We performed genetic examination including comprehensive investigation of X chromosome inactivation and DNA methylation profiling at imprinted loci and genome-wide. RESULTS: Two patients showed comparable clinical features to those in a previous report, indicating that haploinsufficiency of CTCF was the major determinant of the microdeletion syndrome. Despite the haploinsufficiency of CTCF, X chromosome inactivation was normal. DNA methylation at imprinted loci was normal, but hypermethylation at CTCF binding sites was demonstrated, of which PRKCZ and FGFR2 were identified as candidate genes. CONCLUSIONS: This study confirms that haploinsufficiency of CTCF causes distinct clinical features, and that a microdeletion encompassing CTCF could cause a recognisable CTCF deletion syndrome. Perturbed DNA methylation at CTCF binding sites, not at imprinted loci, may underlie the pathomechanism of the syndrome.
Subject(s)
CCCTC-Binding Factor/genetics , Gene Deletion , Genetic Association Studies , CCCTC-Binding Factor/metabolism , Child, Preschool , Comparative Genomic Hybridization , DNA Methylation , Epigenesis, Genetic , Facies , Female , Haploinsufficiency , Humans , In Situ Hybridization, Fluorescence , Phenotype , Sequence Analysis, DNA , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Syndrome , X Chromosome InactivationABSTRACT
BACKGROUND: Airway immunopathogenesis is unclear in patients with profound multiple disabilities (PMD) who undergo tracheostomy. METHODS: The levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8, IL-10, and IL-12p70 cytokines were determined in sputum of 28 patients with PMD who underwent tracheostomy and in 14 healthy subjects, using a cytometric bead array. RESULTS: The concentrations of IL-1beta, IL-6 and IL-8 in the patients were significantly higher than those in controls (p < 0.001). IL-6, and IL-8 levels in eight PMD patients in the febrile period were significantly higher than those in the afebrile period (p < 0.01 and p < 0.05, respectively). Serum CRP levels were slightly elevated in 12 of the 28 patients (43%) in the afebrile period, but there were no significant differences in the level of any cytokine between patients with normal and elevated serum CRP. CONCLUSION: PMD patients with tracheostomy have chronic airway inflammation.
Subject(s)
Cytokines/metabolism , Disabled Persons , Inflammation , Sputum/immunology , Tracheostomy , Adolescent , Adult , C-Reactive Protein/metabolism , Child , Child, Preschool , Female , Humans , Male , Microarray Analysis , Middle Aged , Trachea/immunology , Trachea/pathology , Trachea/surgeryABSTRACT
A 10-year-old girl with a patent ductus venosus associated with multiple autoimmune disorders presented with hypoxia, cyanosis of her lips, and exertional dyspnea. Ultrasonography and abdominal computed tomography of the liver showed a communication between the portal vein and the inferior vena cava through a patent ductus venosus. Portography showed flow from the portal vein directly into the inferior vena cava via the portosystemic shunt. The portosystemic venous shunt ratio was estimated to be 71.8% by scintigraphy using 123I-IMP. Intraoperatively, the authors diagnosed this portosystemic shunt as patent ductus venosus because of the absence of the ductus venosus on real anatomic position. The portal venous pressure was 8.2 cm H2O, which increased to 17.7 cm H2O when the ductus venosus was temporarily occluded. After surgical ligation of the ductus venosus, the color of liver improved, indicating restored liver circulation. The postoperative course was uneventful, and the patient has been asymptomatic for 6 months.
Subject(s)
Portal Vein/abnormalities , Vena Cava, Inferior/abnormalities , Child , Female , Humans , Liver/diagnostic imaging , Liver/pathology , Portal Vein/diagnostic imaging , Radiography , Ultrasonography , Vascular Diseases/diagnosis , Vascular Diseases/therapy , Vena Cava, Inferior/diagnostic imagingABSTRACT
Diffuse pulmonary microvascular arteriovenous communication developed in an 8-year-old girl with a patent ductus venosus. Tc-99m macroaggregated albumin (MAA) pulmonary perfusion scintigraphy with total-body imaging demonstrated multiple lung perfusion deficits and abnormal tracer uptake in systemic organs with hepatic radioactivity greater than the kidneys, suggesting the presence of right-to-left shunt and abnormal hepatic hemodynamics. I-123 iodoamphetamine transrectal portal scintigraphy revealed a large portosystemic venous shunt. The follow-up Tc-99m MAA perfusion scans after banding of the patent ductus venosus revealed partial improvement of the perfusion deficits and right-to-left shunt, indicating the possible reversibility of this pulmonary shunt complication.
