Biomedical subjects
R W Marion
Publications and source records attributed to R W Marion.
Apparent dominant transmission of the Rubinstein-Taybi syndrome.
The cause of the Rubinstein-Taybi syndrome (RTS), a multiple congenital anomalies/mental retardation (MCA/MR) syndrome first described in 1963, remains obscure. Recently, a deletion of chromosomal material at 16p13.3 has been found in some patients with the disorder, but no such deletion can be identified in the majority of affected individuals. Although the disorder has been well documented to be concordant in at least 7 monozygotic twin pairs and in one non-twin sib pair, only one clear-cut case of parent-to-child transmission has been reported previously. We present here a mother and daughter, both of whom appear to be affected with RTS, strongly suggesting either autosomal or X-linked dominant transmission. The paucity of previous cases of parent-to-child transmission may be related to either decreased fertility or decreased fitness in affected individuals.
Gastrointestinal and renal malformations associated with prenatal exposure to alcohol and other teratogens.
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Late-onset psychosis in the velo-cardio-facial syndrome.
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DNA testing for neurofibromatosis type 1.
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The genetic anatomy of hearing. A clinician's view.
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Detection and enumeration of colonic mucosal cells in amniotic fluid using a colon epithelial-specific monoclonal antibody.
Since its introduction, prenatal diagnosis of chromosomal and metabolic disorder by midtrimester amniocentesis has relied upon the use of a mixture of fetal cells obtained from amniotic fluid. Little knowledge has been gained in the sorting of these cells for diagnosis of tissue-specific disorders. In an attempt to determine the contribution of fetal colonic mucosal cells to the overall amniocyte population, we used the colonic epithelial-specific monoclonal antibody (MC-Ab) 7E12H12, IgM isotype. Specimens of the small intestine, colon, buccal mucosa, kidney, urinary bladder, and umbilical cord were obtained from electively aborted normal fetuses of 12-28 weeks' gestation. All of these specimens were examined with 7E12H12 by the immunoperoxidase technique. The MC-Ab reacted with the colonic epithelial cells but not with any of the other tissues. In addition, 40 amniotic fluid samples obtained from women between 16 and 18 weeks of gestation, who underwent amniocentesis because of advanced maternal age, were tested using a fluorescent activated cell sorter. Among the amniotic fluid specimens examined, 18.4 +/- 10.3 per cent cells reacted with 7E12H12. Double immunofluorescence studies revealed that all Mc-Ab-stained cells contained secretory component, confirming that they were epithelial in origin. All fetuses whose amniotic fluid was analysed had normal karyotypes and amniotic fluid alpha-fetoprotein levels that were also normal. This study demonstrates that cell-specific Mc-Ab can be used to detect colon cells in the amniotic fluid and that colon cells contribute significant numbers in the mixture of amniotic fluid cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial infarction leading to sudden death in the Williams syndrome: report of three cases.
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Spondyloepiphyseal dysplasia congenita: genetic linkage to type II collagen (COL2AI).
Spondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominantly inherited chondrodysplasia characterized by disproportionate short stature (short trunk), abnormal epiphyses, and flattened vertebral bodies. Manifestations are present at birth. We ascertained a 4-generation family exhibiting the clinical manifestations of the disorder. Previous evidence suggesting defects of type II collagen associated with the SEDC phenotype led us to genotype the family for various COL2A1 gene-associated RFLPs. A total of 17 affected and unaffected members of this family were studied. The family was informative for a recently discovered HinfI RFLP. No recombinants between the marker and the phenotype were found in eight informative meioses. A maximum LOD score of 3.01 was obtained at a recombination fraction of .00. Our results indicate that the SEDC phenotype in this family is caused by mutations in or very close to the COL2A1 locus.
Limb deficiency in an infant with Smith-Lemli-Opitz syndrome.
We describe a 46,XY newborn infant with Smith-Lemli-Opitz syndrome (SLOS) with multiple congenital anomalies including female external genitalia, a testis palpable in each labium majus, a cone-shaped cervix, and normal vagina. Additional anomalies included cleft palate, total anomalous pulmonary venous return, and striking limb defects (ectrodactyly of the left upper limb, radial aplasia, and monodactyly of the right upper limb). To our knowledge, this is the first report of SLOS associated with limb deficiency and the third associated with total anomalous pulmonary venous return. Our patient demonstrates that limb deficiencies may be a rare component manifestation in this syndrome of multiple congenital anomalies.
A piece of my mind. When Tom died.
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Variable expression in focal dermal hypoplasia. An example of differential X-chromosome inactivation.
We encountered three women from three generations of the same family with features of focal dermal hypoplasia (FDH). Two of the patients, the proposita and her mother, demonstrated severe manifestations, including skin, dental, skeletal, and visceral abnormalities. The proposita's grandmother, the first family member affected, had very mild expression, with aplasia cutis congenita and dental caries as the only features expressed. This family illustrates both the marked variability of expression and the proposed X-linked dominant mode of inheritance of FDH. We postulate that early embryologic random inactivation of the X chromosome bearing the mutant gene responsible for FDH is the cause of the variable expression.
Aspartylglucosaminuria in a Puerto Rican family: additional features of a panethnic disorder.
We report on 3 Puerto Rican brothers with the clinical and laboratory findings of aspartylglucosaminuria (AGU). Their parents were first cousins. The affected sibs have the "cardinal" manifestations of AGU, including developmental disabilities, progressive "coarsening" of the face, and early onset of hepatosplenomegaly. Biochemical studies showed elevated levels of urinary aspartylglucosamine and very low activity of aspartylglucosaminidase(AGA) in cultured fibroblasts. With long term follow-up, previously undescribed manifestations were noted, including radiographic evidence of spondylolysis and spondylolisthesis in early childhood and development of macro-orchidism during puberty. This family shows that AGU is not limited to individuals of Finnish background, but that the gene is panethnic in distribution and that additional changes, not previously noted, may present with advancing age.
Explanation for fetal baseline bradycardia in a fetus with panhypopituitarism and other malformations.
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Craniofacial dysmorphism in children with human immunodeficiency virus infection.
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Trisomy 18 score: a rapid, reliable diagnostic test for trisomy 18.
We developed a bedside scoring system for diagnosis of trisomy 18 in the immediate neonatal period. Points are assigned for the presence of features known to occur in trisomy 18: five points for the presence of features previously reported in 50% or more of affected infants; three points for features reported to occur in between 10% and 50% of affected individuals; and one point for features known to occur in less than 10% of infants with the disorder. Using the scoring system, we evaluated two cohorts of patients: those in whom a diagnosis of trisomy 18 was previously established (retrospective group) and those in whom the diagnosis was suspected but not yet proved (prospective group). The average score in the retrospective series (n = 25) was 96.7, and no patient scored less than 70. Twenty-two patients were evaluated prospectively; in all cases the presence or absence of trisomy 18 was correctly predicted. The average score in the 11 patients without trisomy 18 was 41.4, and all patients scored 60 or less. In the 11 patients confirmed to have trisomy 18, the average score was 94.3, with a range of 70 to 113. This scoring system is an accurate, reproducible method for predicting trisomy 18 in neonates with multiple congenital malformations.
Fetal AIDS syndrome score. Correlation between severity of dysmorphism and age at diagnosis of immunodeficiency.
To objectively evaluate the fetal acquired immunodeficiency syndrome, we have developed a scoring system based on the presence of the characteristic features that we have previously reported. Using this scoring system, 37 children seropositive for the human immunodeficiency virus were classified into three groups: dysmorphologically severely affected (12 children); moderately affected (15 children); and mildly affected (ten children). There was a statistically significant correlation between the severity of the dysmorphic features and both the presence of opportunistic infections within the first year of life and the age at onset of symptoms associated with immune dysfunction, with the more severely stigmatized children manifesting symptoms at a younger age. There was no correlation, however, between severity of the dysmorphic features and presence of opportunistic infections at the time of our examination. We conclude that this scoring system may be useful in presymptomatic identification of severely dysmorphic human immunodeficiency virus-infected infants.