acid-phosphatase and Heart-Defects--Congenital

Congenital heart disease (CHD), comprising structural or functional abnormalities present at birth, is the most common birth defect in humans. Reduced expression of connexin40 (Cx40) has been found in association with atrial fibrillation, and deletion of Cx40 in a mouse model causes various structural heart abnormalities in 18% of heterozygotes. We screened 505 unrelated CHD cases for deletions or duplications of the Cx40 gene (GJA5) by real-time quantitative PCR, in order to determine whether altered copy number of this gene may be associated with a cardiac phenotype in humans. Dosage of Cx40 flanking genes (ACPL1 and Cx50 gene, GJA8) was determined by real-time PCR for all apparent positive cases. In total, 3 cases were found to carry deletions on chromosome 1q21.1 spanning ACPL1, Cx40, and Cx50 genes. Absence of heterozygosity was observed in all 3 index cases over a 1.5- to 3-Mb region. Samples from the parents of two cases were obtained, and microsatellites across 1q21.1 were genotyped. One of the apparently unaffected parents was found to carry this deletion. All 3 index cases presented with obstruction of the aortic arch as the common structural cardiac malformation, and had no consistent dysmorphic features. Genotyping of 520 unrelated normal controls for this deletion was negative. We hypothesize that this 1q21.1 multigene deletion is associated with a range of cardiac defects, with anomalies of the aortic arch being a particular feature.

Topics: Acid Phosphatase; Adolescent; Adult; Animals; Aorta, Thoracic; Child; Child, Preschool; Chromosomes, Human, Pair 1; Computer Systems; Connexins; Eye Proteins; Female; Gap Junction alpha-5 Protein; Gene Deletion; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Loss of Heterozygosity; Male; Mice; Microsatellite Repeats; Models, Animal; Penetrance; Polymerase Chain Reaction

Topics: Acid Phosphatase; Aorta; Child, Preschool; Cyanosis; Erythrocytes; Glucosephosphate Dehydrogenase; Heart Defects, Congenital; Humans; Hypoxia; Infant; Infant, Newborn; Pulmonary Artery; Tetralogy of Fallot; Transposition of Great Vessels

Topics: Acid Phosphatase; Adult; Amniocentesis; Cardiomegaly; Female; Fetal Diseases; Genes, Recessive; Glucose; Glucosidases; Glycogen Storage Disease; Heart Defects, Congenital; Heart Diseases; Heterozygote; Humans; Infant, Newborn; Lectins; Lymphocytes; Male; Myocardium; Pregnancy; Prenatal Diagnosis; Syndrome; Time Factors

Ceramidase activity could not be demonstrated in the kidney and cerebellum from a deceased patient with Farber's disease, whereas the activities of six control acid hydrolase enzymes appeared normal. This enzyme defect presumably accounts for the accumulation that has been described in two patients and may represent the biochemical basis of this disorder.

Topics: Acid Phosphatase; Adult; Carbon Isotopes; Ceramides; Cerebellum; Cerebrosides; Child; Child, Preschool; Congenital Abnormalities; Female; Galactose; Galactosidases; Glucose; Glycoside Hydrolases; Heart Defects, Congenital; Hexosaminidases; Humans; Hydrolases; Infant; Infant, Newborn; Intellectual Disability; Kidney; Lipidoses; Liver Cirrhosis, Biliary; Male; Metabolism, Inborn Errors; Neuraminidase; Pigmentation Disorders; Respiratory Distress Syndrome, Newborn