| growth hormone (GH) insensitivity is a heterogeneous condition that can result from mutations within the GH receptor (GHR) and that can be inherited as both an autosomal recessive and a dominant trait. However, evidence from a small number of growth hormone binding protein (GHBP)-positive families indicates that their GH insensitivity is independent of GHR mutations. Two of these families appear to have distinct abnormalities in GH signal transduction. Studies suggest that one family (classic laron syndrome phenotype; designated family H) have a signalling defect close to the GHR, preventing activation of both the STAT and MAPK pathways, whereas the other family (less marked phenotype; family M) have a defect in activating MAPK but not the STAT pathway. The children studied here are specifically insensitive to GH and their defect must be exclusive to this signalling system. Thus, families with GHBP-positive GH insensitivity without GHR mutations are likely to be important models in which to study the specificity of GH signal transduction and the relationship between GH insensitive phenotype and signalling defect. ( info) |
2/163. Autosomal dominant optic atrophy with unilateral facial palsy: a new hereditary condition? A mother and daughter are reported with bilateral optic atrophy with onset in infancy and unilateral facial palsy. This appears to be a novel autosomal dominant disorder. ( info) |
| coffin-lowry syndrome is an X-linked recessive syndrome of mental retardation, characteristic facies and skeletal anomalies. In one patient with the syndrome, we observed early recurrent episodes of congestive heart failure with intercurrent normalization and the late development of mitral insufficiency due to annular dilation and congenital abnormalities of the valve apparatus. This unusual course of cardiac involvement, the non-adaptation of the left ventricular contractility to the aggravation of the mitral insufficiency and the postoperative persistence of the ventricular dysfunction, underline the possible role of an associated primary myocardial disease. This clinical observation demonstrates clearly that a mitral valve malformation can occur in patients with the syndrome, but also the role of a dilated cardiomyopathy, which can be secondary to the mitral regurgitation, but is more likely a myocardial disorder occurring as part of the syndrome. ( info) |
4/163. May-Hegglin anomaly in a pregnancy complicated by intrauterine growth restriction and ambiguous genitalia. OBJECTIVE: thrombocytopenia as a hematologic disorder complicates up to 4% of all pregnancies. May-Hegglin anomaly is a rare cause of low platelets in pregnancy. methods: A case of May-Hegglin anomaly complicating pregnancy and intrauterine growth restriction in a fetus with ambiguous genitalia is described. RESULTS: The antepartum and intrapartum diagnosis and management of a patient diagnosed with May-Hegglin anomaly is discussed. The involvement and consultation of a perinatologist, neonatologist, internist, and anesthesiologist is reviewed, with emphasis on the mode of delivery. CONCLUSION: The potential maternal and fetal complications associated with May-Hegglin anomaly warrant early pregnancy diagnosis and access to a tertiary care facility. ( info) |
5/163. The risk of birth defects: Jacobs v. Theimer and parents' right to know. This Article discusses the texas Supreme Court's holding in Jacobs v. Theimer that the parents of a defective child had a cause of action for damages against a physician for alleged negligent failure to inform the mother during pregnancy that she had contracted rubella and therefore might have a defective child, thereby causing her to lose the opportunity to have an abortion. The Article raises a number of questions that post-Jacobs courts probably will confront concerning the duty of physicians and genetic counselors to keep their clients informed; describes some social and medical developments--including recent progress in medical genetics and prenatal diagnosis--which are likely to make Jacobs a significant precedent; evaluates the court's decision to allow a damage suit only for the costs of treating and caring for the child's defects; and briefly addresses the question of whether the Jacobs case comes within the sphere of suits for what has come to be known as "wrongful birth" and "wrongful life." ( info) |
6/163. Familial idiopathic adulthood ductopenia: a report of five cases in three generations. BACKGROUND/AIMS: Idiopathic adulthood ductopenia is a cholestatic liver disease of unknown etiology. Although most cases are sporadic, familial cases do occur. methods: We describe a series of adult-onset bile duct depletion involving five members of an extended family spanning three generations. The proband, a 49-year-old man, presented in 1989 with asymptomatic elevation of liver enzyme tests. Investigations for chronic liver disease, including endoscopic retrograde cholangiopancreatography, were negative. Findings on liver biopsy progressed from normal in 1989 to striking loss of interlobular bile ducts in 1992. ursodeoxycholic acid has resulted in improvement of liver enzyme tests. The proband's brother required a liver transplant at age 35 for cryptogenic cirrhosis. The proband's sister, age 42, has had intermittent jaundice and elevation of liver enzyme tests since 1971. Her liver biopsy findings progressed from normal in 1975, to striking bile duct damage by 1997. The proband's 21-year-old son has elevated liver enzyme tests and a liver biopsy consistent with idiopathic adulthood ductopenia. The proband's father had a liver biopsy at age 70 for investigation of a liver mass. It revealed extensive fibrosis and striking bile duct destruction. RESULTS/CONCLUSIONS: This is the largest series of familial idiopathic adulthood ductopenia reported, and the first with multiple generations described. genetics appears to play a role in some cases of adulthood ductopenia. ursodeoxycholic acid may be beneficial in the treatment of this condition. ( info) |
7/163. Multiple mtDNA deletions: clinical and molecular correlations. We studied six Italian patients harbouring multiple mitochondrial dna (mtDNA) deletions in order to correlate clinical and molecular features. Earlier age at onset (17 vs 36 years), fewer ragged-red fibres (none vs 35%), and lower proportions of deleted mtDNAs (9 vs 33%) were found in one patient with autosomal recessive inheritance as compared to five with dominant transmission. Our findings add to the features associated with multiple deletions of mtDNA. ( info) |
8/163. Concurrent factor v Leiden and prothrombin G20210A gene mutations in a patient with a history of recurrent thrombosis. We report a case of a 35-year-old male with a history of recurrent thromboembolic events, who presented to the emergency room with right sided weakness and difficulty with speech. The patient's past medical history included two myocardial infarctions, two deep vein thromboses, and a pulmonary embolism. Subsequent laboratory evaluation indicated that the patient was heterozygous for both the factor v Leiden and prothrombin G20210A mutations. This case report emphasizes the importance of evaluating patients with suspected hereditary thrombophilia for both of these mutations. ( info) |
9/163. "Talon cusp-heredity origin"--a case report. Talon cusp is a very unusual anomalous structure of tooth. The etiology is still unknown. It may be due to mal-interaction between ecto and mesoderm of epithelial bulgings present on premaxillary region at the time of complex odontogenesis. genetics may have some role in the formation of Talon cusp. Talon cusp may cause clinical complications. ( info) |
10/163. A novel mutation in the flavin-containing monooxygenase 3 gene, FM03, that causes fish-odour syndrome: activity of the mutant enzyme assessed by proton NMR spectroscopy. We have previously shown that primary trimethylaminuria, or fish-odour syndrome, is caused by an inherited defect in the flavin-containing monooxygenase 3 (FMO3) catalysed N-oxidation of the dietary-derived malodorous amine, trimethylamine (TMA). We now report a novel causative mutation for the disorder identified in a young girl diagnosed by proton nuclear magnetic resonance (NMR) spectroscopy of her urine. sequence analysis of genomic dna amplified from the patient revealed that she was homozygous for a T to C missense mutation in exon 3 of the FMO3 gene. The mutation changes an ATG triplet, encoding methionine, at codon 82 to an ACG triplet, encoding threonine. A polymerase chain reaction/restriction enzyme-based assay was devised to genotype individuals for the FMO3Thr82 allele. Wild-type and mutant FMO3, heterologously expressed in a baculovirus-insect cell system, were assayed by ultraviolet spectrophotometry and NMR spectroscopy for their ability to catalyse the N-oxidation of TMA. The latter technique has the advantage of enabling the simultaneous, direct and semi-continuous measurement of both of the products, TMA N-oxide and nadp, and of one of the reactants, NADPH. Results obtained from both techniques demonstrate that the Met82Thr mutation abolishes the catalytic activity of the enzyme and thus represents the genetic basis of the disorder in this individual. The combination of NMR spectroscopy with gene sequence and expression technology provides a powerful means of determining genotype-phenotype relationships in trimethylaminuria. ( info) |