ABSTRACT
The Say-Barber-Biesecker-Young-Simpson variant of Ohdo syndrome (SBBYSS) (MIM# 603736) and genitopatellar syndrome (GPS) (MIM#606170) are allelic diseases caused by KAT6B mutation. Genotype-phenotype correlation is assumed, but a few patients manifest overlapping features of both syndromes. Here we report the case of a boy with SBBYSS. He had a KAT6B mutation previously reported in typical SBBYSS, but he also manifested severe developmental delay, as well as genital features and laryngomalacia requiring tracheostomy that conformed to GPS.
Subject(s)
Blepharophimosis/diagnosis , Blepharophimosis/genetics , Congenital Hypothyroidism/diagnosis , Congenital Hypothyroidism/genetics , Gene Duplication , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/genetics , Histone Acetyltransferases/genetics , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Inverted Repeat Sequences , Joint Instability/diagnosis , Joint Instability/genetics , Alleles , Craniofacial Abnormalities/diagnosis , DNA Mutational Analysis , Diagnosis, Differential , Exons , Facies , Genetic Association Studies , Humans , Infant, Newborn , Kidney/abnormalities , Male , Mutation , Patella/abnormalities , Phenotype , Psychomotor Disorders/diagnosis , Radiography , Scrotum/abnormalities , Ultrasonography, Prenatal , Urogenital Abnormalities/diagnosisABSTRACT
BACKGROUND: Infantile neuronal ceroid lipofuscinosis (INCL) is an autosomal recessive disorder starting in infancy as early as 12-month-old, caused by PPT1 (palmitoyl-protein thioesterase 1) mutations, and characterized by progressive psychomotor deterioration, brain atrophy, myoclonic jerk and visual impairment. INCL can be diagnosed by brain magnetic resonance image (MRI) prior to rapid deterioration stage. To date, there is no INCL patient whose manifestation was caused by uniparental isodisomy (UPiD). PATIENT: We reported a girl diagnosed with INCL. Genetic analysis revealed a novel PPT1 mutation c.20_47del28:p.Leu7Hisfs*21. Only the father of the patient was found as a carrier of this mutation. SNP array showed the mutation became homozygous by paternal UPiD of chromosome 1. DISCUSSION: Although ICNL is a rare disease except in Finland, it is not difficult to diagnose it since the clinical symptoms and MRI findings are characteristic. Genetic testing is useful for definitive diagnosis, and distinction of UPiD is essential for genetic counseling.
Subject(s)
Chromosomes, Human, Pair 1 , Membrane Proteins/genetics , Neuronal Ceroid-Lipofuscinoses/genetics , Neuronal Ceroid-Lipofuscinoses/physiopathology , Uniparental Disomy/genetics , Uniparental Disomy/physiopathology , Brain/diagnostic imaging , Child, Preschool , Diagnosis, Differential , Female , Frameshift Mutation , Humans , Infant , Magnetic Resonance Imaging , Neuronal Ceroid-Lipofuscinoses/diagnosis , Oligonucleotide Array Sequence Analysis , Polymorphism, Single Nucleotide , Thiolester Hydrolases , Uniparental Disomy/diagnosisABSTRACT
Tau protein levels in cerebrospinal fluid (CSF) and serum are elevated in patients with various central nervous system diseases. We investigated whether serum tau protein levels are useful for predicting and assessing disease activity of acute encephalopathy (AE) in enterohemorrhagic Escherichia coli (EHEC) O111-induced hemolytic uremic syndrome (HUS; EHEC encephalopathy). Serum samples were obtained from 14 patients with EHEC O111/HUS, 20 patients with non-EHEC-related AE, and 20 age- and sex-matched healthy controls. CSF samples were obtained from 2 patients with EHEC encephalopathy and 20 patients with non-EHEC-related AE. Tau protein levels and levels of several proinflammatory cytokines were quantified by enzyme-linked immunosorbent assays. Results were compared with the clinical features of EHEC encephalopathy, including magnetic resonance image (MRI) findings. Serum tau levels in patients with EHEC encephalopathy were significantly elevated compared with those in patients with EHEC O111/HUS without encephalopathy, patients with non-EHEC-related AE, and healthy controls. The ratio of CSF tau levels to serum tau levels was >1.0 in all patients with non-EHEC-related AE but <1.0 in 2 patients with EHEC encephalopathy. Serum tau protein levels increased rapidly and markedly in patients with severe EHEC 0111/HUS and encephalopathy when HUS occurred, but were not elevated in mild patients, even in the HUS phase. Furthermore, changes in serum tau protein levels in patients with EHEC encephalopathy were consistent with abnormalities on brain MRI and were positively correlated with proinflammatory cytokine levels. Our results indicate that serum tau protein might be useful to predict and assess disease activity of EHEC encephalopathy.
Subject(s)
Enterohemorrhagic Escherichia coli/pathogenicity , Escherichia coli Infections/epidemiology , Hemolytic-Uremic Syndrome/epidemiology , tau Proteins/blood , Adolescent , Adult , Child , Disease Outbreaks , Escherichia coli Infections/pathology , Female , Hemolytic-Uremic Syndrome/pathology , Humans , Infant , Japan/epidemiology , Magnetic Resonance Imaging , MaleABSTRACT
GATA3 is a member of the GATA family of transcription factors. Heterozygous GATA3 abnormalities are associated with hypoparathyroidism, sensorineural deafness, and renal abnormality (HDR syndrome). However, this triad of symptoms does not occur in all HDR patients and other clinical features may be present in some cases. We report the clinical phenotypes and the molecular analysis of GATA3 in five Japanese HDR patients, including two familial cases. All five patients had hypoparathyroidism and sensorineural deafness, however renal abnormalities were absent in four patients. In addition, two patients with different mutations of GATA3 had female genital tract abnormalities. Sequence analysis of GATA3 demonstrated three novel (R262G, c1063delC and C318) and two reported mutations (c.432insG and c.1051-1G>T). Transient transfection assay using the GATA3 activating reporter system revealed that the transactivating activity of the R262G, c.1063delC, C318S and c.432insG mutants were markedly decreased, indicating that all four mutations are loss-of-function. In conclusion, this study reiterates the clinical variability in HDR syndrome and identifies three novel mutations of GATA3.
Subject(s)
GATA3 Transcription Factor/genetics , Adolescent , Adult , Child , DNA/analysis , Female , Genitalia, Female/abnormalities , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/genetics , Heterozygote , Humans , Hypoparathyroidism/diagnosis , Hypoparathyroidism/genetics , Infant , Japan , Kidney/abnormalities , Male , Nephrosis/diagnosis , Nephrosis/genetics , Pedigree , Phenotype , Polymerase Chain Reaction , Sequence Analysis, DNAABSTRACT
In chronic active Epstein-Barr virus (EBV) infection (CAEBV), ectopic EBV infection has been described in T or natural killer (NK) cells. NK cell-type infection (NK-CAEBV) is characterized by large granular lymphocytosis, high IgE levels and unusual reactions to mosquito bites, including severe local skin reactions, fever and liver dysfunction. However, the mechanisms underlying these reactions remain undetermined. Herein, we describe a patient with NK-CAEBV whose blister fluid after mosquito bites was analyzed. The patient exhibited significant increases in the percentage of CD56(+) NK cells in the fluid compared with a simple mosquito allergy, in which the majority of infiltrated cells were CD203c(+) cells, indicating basophils and/or mast cells. His fluid also contained CD203c(+) cells, and his circulating basophils were activated by mosquito extracts in vitro. These results suggest that CD203c(+) cells as well as NK cells may play pathogenic roles in the severe skin reactions to mosquito bites in NK-CAEBV.
