ABSTRACT
Many neurodevelopmental disorders are caused by the presence of CNVs. Chromosome microarray technology is widely used to accurately detect CNVs. We report the case of a male, aged 3 years, presenting with delayed psychomotor development, generalized hypotonia, encephalopathy, delayed myelination in the central nervous system, and poor motor coordination. The array CGH revealed an interstitial deletion of chromosome 19q13.2 with a size of 88.8 kb involving 3 OMIM genes: RABAC1, ARHGEF1, and ATP1A3. Heterozygous mutations in the ATP1A3 gene are associated with delayed psychomotor development, alternating hemiplegia of childhood type 2 (AHC2), dystonia type 12, and cerebellarataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome, also called CAPOS syndrome. The phenotypic expression of partial ATP1A3 deletion is, however, poorly described in the literature. The deletion was confirmed by MLPA, and we identified a hitherto undescribed novel deletion of exons 3b-21 of the ATP1A3 gene. Our data suggest that the deletion of the ATP1A3 gene is a causative factor of the AHC2 phenotype in the patient.
ABSTRACT
We report three cases of patients with pseudohypoparathyroidism or pseudopseudohypoparathyroidism. These diseases are considered GNAS inactivating mutation syndromes that are characterized by a diversity of alterations among which a particular phenotype and specific endocrine or ossification abnormalities may be found. These patients may present with hard cutaneous nodules, which can represent osteoma cutis. The presence of these lesions in pediatric patients should prompt the dermatologist's consideration of this group of diseases when reaching a diagnosis. A multidisciplinary team of pediatricians, endocrinologists, geneticists, and dermatologists should carefully evaluate these patients.
Subject(s)
Pseudohypoparathyroidism/complications , Pseudohypoparathyroidism/diagnosis , Pseudopseudohypoparathyroidism/complications , Pseudopseudohypoparathyroidism/diagnosis , Skin Diseases/etiology , Adolescent , Child , Female , Humans , Male , Skin Diseases/diagnostic imaging , Skin Diseases/pathologyABSTRACT
No disponible
Subject(s)
Humans , Male , Adolescent , Adult , Brugada Syndrome/genetics , Gene Deletion , Death, Sudden, Cardiac/epidemiology , Genetic Diseases, InbornSubject(s)
Brugada Syndrome/genetics , DNA/genetics , Genetic Predisposition to Disease , Mutation , NAV1.5 Voltage-Gated Sodium Channel/genetics , NAV1.8 Voltage-Gated Sodium Channel/genetics , Adolescent , Brugada Syndrome/metabolism , DNA Mutational Analysis , Electrocardiography , Humans , Male , NAV1.5 Voltage-Gated Sodium Channel/metabolism , NAV1.8 Voltage-Gated Sodium Channel/metabolism , PedigreeABSTRACT
OBJECTIVE: Wide interindividual variability exists in response to tissue plasminogen activator (t-PA) treatment in the acute phase of ischemic stroke. We aimed to find genetic variations associated with hemorrhagic transformation (HT) and mortality rates after t-PA. We then generated a clinical-genetic model for predicting t-PA response. METHODS: Our prospective study used SNPlex to genotype 140 single nucleotide polymorphisms (SNPs) from 97 candidate genes in 3 patient cohorts. The cohorts included 1,172 patients who were treated with t-PA; 20.9% of them developed HT as evaluated by systematic brain computed tomography scan, and 10.6% died. A predictive model was generated by logistic regression (LR). Functional studies included real time quantitative polymerase chain reaction, nephelometry, and Western blot for alpha-2-macroglobulin (A2M) and activated partial thromboplastin time measurement for coagulation factor XII (FXII). RESULTS: Replication analysis revealed that the SNP rs669 (Val1000Ile) in A2M was associated with HT, and rs1801020 (-4C>T) of F12 was associated with in-hospital death. The rs669 SNP withstood Bonferroni correction for HT (p < 3.57E-4). LR-based scores predicted HT occurrence (p = 9.13E-15) and in-hospital mortality (p = 8.7E-9) and were validated in an independent cohort. Val1000Ile modified A2M serum levels at baseline and after t-PA infusion, but not mRNA expression or protein structure; -4C>T affected FXII activity both prior to and after t-PA treatment. INTERPRETATION: Two functional polymorphisms were consistently associated with t-PA safety. Our validated LR-based score predicts t-PA safety in the Spanish population.
