bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two chromosome aberrations in the child of a woman with systemic lupus erythematosus treated with azathioprine and prednisone
Authors: Ostrer H. , Stamberg J. , Perinchief P. , Opitz John M. 
Published: June 2005

AbstractA boy with microcephaly, unusual facial features, micropenis, and growth retardation was born to a 30‐year‐old woman who took azathioprine and prednisone before and during pregnancy for systemic lupus erythematosus. The child has two apparently de novo chromosomal abnormalities: an apparently balanced translocation between chromosomes 6 and 14 and an interstitial deletion of chromosome 7. The karyotype is 46,XY,del(7)(q21);t(6;14)(q21;q12). Use of azathioprine and prednisone in pregnancy has been associated with intrauterine growth retardation, congenital malformations, and transient chromosome breaks in the blood of newborns. To our knowledge, this is the first report of de novo constitutional chromosome abnormalities in such an infant. We suggest that the assessment of infants born to parents treated with azathioprine should include a chromosome study, even if the infants seem to be normal.
Psychological aspects of genetic counseling. III. Management of guilt and shame
Authors: Kessler Seymour , Kessler Hilda , Ward Patricia , Opitz John M. 
Published: June 2005

AbstractReactions of guilt and shame are conspicuous in the context of genetic counseling, and the relief of their distressing aspects is a widely held goal of genetic counselors. They are in a unique position to accomplish this; however, guidelines as to how one might proceed are not readily available. We have considered guilt and shame responses and have attempted to differentiate them, dynamically and developmentally, and have pointed out how each might be manifested in the course of genetic counseling. The major counseling tactics by means of which the alleviation or reduction of feelings of guilt and shame might be achieved are outlined and case illustrations are provided in which actual and potential counseling situations are explored and discussed.
Ethical considerations in medical genetics–the prenatal diagnosis of hemophilia B
Authors: Smurl James F. , Weaver David D. , Jarmas Audre , Padilla Lillie‐Mae , Optiz John M. 
Published: June 2005

AbstractA couple is presented who underwent prenatal counseling and amniocentesis for sex determination because the wife was an obligate carrier of hemophilia B. Although the fetus was determined to be male, the parents elected not to have further testing to determine if he had hemophilia or not.The difficulties in the in utero diagnosis of hemophilia B are presented and discussed. In addition, the moral reasoning and decision‐making process that this couple went through regarding the decision not to have further fetal testing and to continue the pregnancy is presented and analyzed. These moral decisions appear to be based on family and personal ties, and bonding to the fetus after perception of fetal movement. They combine considerations of the duties and rights involved in such situations, and attend to the anticipated consequences as well.
The dynamics of quantifiable homeostasis. III: A linear model of certain metrical diseases
Authors: Renie William A. , Murphy Edmond A. 
Published: June 2005

AbstractA generalization of the linear, lagged, homeostatic process shows that whether a displacement of the trait function dies out with time, continues indefinitely, or shows a steadily amplifying (wild) oscillation depends on the value assumed by the product of the lag time and the restoration constant. Moreover, it is shown that if a steady displacing force is used rather than an instantaneous displacement, a new homing value results which is given by the ratio of the displacing force to the restoration coefficient. Combining these two developments furnishes grounds for determining whether or not an overshoot will occur when administration of a drug is stopped (for instance, the rebound thrombosis on discontinuing heparin). Further developments of these ideas show how the diabetes that begins in mature patients can be wholly accounted for by the well‐known prolongation of the lag in insulin response that occurs in that disorder. If wild oscillation is to be avoided as the lag time increases, the restoration constant must be weakened (evidently by a systematic reduction in insulin receptors) and this weakening means that the homing value is displaced. Thus the hyperglycemia in this diabetes is to be seen as the price paid for avoiding wild oscillation. Provided that the therapeutic use of exogenous insulin is systematic and regular, rather than cybernetic, its success where endogenous (cybernetic) insulin secretion has failed is readily understood. The point is illustrated by a familiar analogy of a car driver with slow responses. The genetic and evolutionary implications of these ideas are outlined.
Trigonocephaly: A new familial syndrome
Authors: Frydman Moshe , Kauschansky Arieh , Elian Ezra , Opitz John M. 
Published: June 2005

AbstractTrigonocephaly was found in six relatives through three generations of one family. The propositus was ascertained at birth because of omphalocele. In addition to trigonocephaly, he had minor ear, vertebral, and genital abnormalities. His father had mild microcephaly, and both had minor eye abnormalities. None of the other four affected individuals had any other malformations. In this family, trigonocephaly is an autosomal dominant trait. The ratio of affected males to affected females was 5 to 1, and although the paucity of affected females is not statistically significant, we speculate that it may reflect variable expressivity or sex limitation of the trait. We conclude that the condition in this family represents a unique syndrome in which trigonocephaly is not associated with functional brain abnormalities and where craniosynostosis is limited to the metopic region.
The natural history of Huntington disease: Possible role of “aging genes”
Authors: Farrer Lindsay A. , Conneally P. Michael , Yu Pao‐Io 
Published: June 2005

AbstractIn this paper we consider a model in which genetic factors that control aging also modify expression of the Huntington disease (HD) gene. Significant correlation coefficients were obtained for age‐at‐onset (AO) and age‐at‐death (AD) between affected parents and their affected offspring. However, more relevant to our hypothesis, the correlations between mean AD in normal sibs and AD in the affected parent (r =.57) and mean AD in their affected sibs (r =.54) are also significant. When onset is used instead of death for affected individuals the coefficients are.46 and.52, respectively. Also, AD in the normal parent is significantly correlated with AD in his affected (r =.39) and normal (r =.36) offspring.Current genetic theories on aging and related trends in HD are discussed. Our results and evidence from gerontological studies support the hypothesis that HD gene carriers with “superior” aging genes manifest symptoms later in life and have increased longevity over those with “inferior” aging genes.
Cyclopia and cebocephaly in two newborn infants with unbalanced segregation of a familial translocation rcp (1;7)(q32;q34)
Authors: Schinzel A. , Opitz John M. 
Published: June 2005

AbstractThis is a report of a family with a balanced reciprocal translocation, rep (1;7)(q32;q34). Among pregnancies from translocation carriers, there were several miscarriages, and two unbalanced offspring with dup(1q32→qter) and del (7q34→qter) who died perinatally. One was a male cyclops with additional brain malformations and hydronephrosis, the other was a cebocephalic female with multiple additional malformations of heart, kidneys, and skeleton. In both pregnancies, the brain and renal anomalies were detected prenatally by ultrasound, in the cyclops during the 32nd and in the cebocephalic fetus during the 28th week of gestation.
A new lipid storage myopathy observed in individuals with the Ruvalcaba‐Myhre‐Smith syndrome
Authors: DiLiberti J. H. , D'Agostino A. N. , Ruvalcaba R. H. A. , Schimschock J. R. , Opitz John M. 
Published: June 2005

AbstractFour patients with the Ruvalcaba‐Myhre‐Smith syndrome (primary macrocephaly with associated anomalies including pigmented macules on the penis in affected males, hamartomatous intestinal polyps, and lipomas) had evidence of delayed psychomotor development and/or hypotonia in childhood. Electromyography in 3 patients showed evidence of a myopathic process. Muscle biopsy in all four demonstrated a lipid storage myopathy with increased numbers of neutral lipid droplets—predominatly in type 1 fibers. The type 2 fibers were consistently smaller than expected. Electron microscopy was unremarkable except for evidence of lipid accumulation. Muscle carnitine and carnitine palmityl transferase levels were normal in one patient. This appears to be a previously unreported type of lipid storage myopathy characteristic of the Ruvalcaba‐Myhre‐Smith syndrome, a probable autosomal dominant trait.
Developmental pathogenesis of chromosome disorders: Report on two newly recognized signs of down syndrome
Authors: Langenbeck U. , Blum Ellen , Wilkert‐Walter Cornelia , Hansmann I. 
Published: June 2005

AbstractTesting the hypothesis of amplified developmental instability in autosomal trisomies as proposed by Shapiro we predicted and found an increased frequency of symphalangies in the toes of patients with Down syndrome. In our X‐ray study of the feet of 71 adults with trisomy 21 we also detected a greater than normal number of sesamoid bones.A corollary to Shapiro's hypothesis is a dependence on ethnic origin of the frequency of symptoms in Down syndrome. Compared to data from Europe, toe symphalangies are more prevalent in Japan. We predict this anomaly to occur even more often in Japanese patients with trisomy 21.
Pyruvate kinase in fetal plasma and amniotic fluid unsuccessful for the prenatal diagnosis of Duchenne muscular dystrophy
Authors: Edwards R. J. , Rodeck C. H. , Watts D. C. 
Published: June 2005

AbstractA specific spectrophotometric assay of muscle‐pyruvate kinase (M‐PK) was used to measure the activity of this isozyme in fetal muscle, fetal plasma and amniotic fluid at about 17–24 wk of gestational age to assess its predictive value for the prenatal diagnosis of Duchenne muscular dystrophy (DMD). Fetal muscle obtained after termination was found to contain a high M‐PK specific activity. No significant activity was detected in amniotic fluid from normal or at‐risk fetuses. Pure fetal blood was obtained in utero by fetoscopy; significant plasma levels of M‐PK activity were measured in a series of control samples, but at‐risk fetal plasma contained no higher levels. We conclude that M‐PK is of no use for the prenatal diagnosis of DMD.
The dynamics of quantifiable homeostasis. V: Homeostasis of higher order
Authors: Renie William A. , Murphy Edmond A. 
Published: June 2005

AbstractThe properties are explored of a cybernetic process with lag L and force of restoration equal to the size of displacement one lag unit earlier, raised to any arbitrary positive power (w > 1), multiplied by the restoration constant b, the sign being opposite to that of the displacement at that time. No closed‐form solution is available, but a converging Taylor series expansion is presented that gives a solution of arbitrary precision. Unlike the linear system previously discussed, the amplitude of the displacement (A) is germane, and it is shown that the criterion that the effect of a perturbation be damped out is whether or not LbAw−1 exceeds a constant, kw, that depends only on w. The counterpart of this pattern of higher‐order homeostasis is closer to the biological behavior of many forms of homeostasis than the scaled invariance characteristic of the linear process. kw is shown to be bounded between π/2 and 2, and increases monotonically with w. Exactly computed values and large‐sample approximations are given for the critical values below which no overshoot at all occurs. It is shown that where it does not, the minimum expected cost decreases with increasing w and reaches a minimum at infinite w. However, this evolutionary gain is vitiated where large displacements are involved, and may need to be redressed by a change in the restoration constant. Thus, the dynamic balance becomes much more subtle than with lower‐order processes. Several brief clinical illustrations of these ideas are presented.
Hereditary pyropoikilocytosis: Report of two cases from Saudi Arabia
Authors: Mallouh Ahmad , Sa'di A. Rahman , Ahmad M. S. , Salamah M. , Opitz John M. 
Published: June 2005

AbstractHereditary pyropoikilocytosis is a rare type of congenital hemolytic anemia reported only in American black children. We report the first two occurrences in Saudi children. This is an autosomal‐recessive trait as proved by normal parents and two affected children. A pathogenetic and probably causal relationship with apparent elliptocytosis seems clear as three sibs have that condition.
Familial external genital ambiguity due to a transformation defect of androgen‐receptor complexes that is expressed with 5α‐dihydrotestosterone and the synthetic androgen methyltrienolone
Authors: Kaufman Morris , Pinsky Leonard , Bowin Adria , Au Mary W. S. 
Published: June 2005

AbstractWe have studied various properties of the binding of 5α‐dihydrotestosterone (DHT) or the synthetic, nonmetabolizable androgen methyltrienolone (R1881; 17β‐hydroxy‐17α‐methylestra‐4, 9,11‐trien‐3‐one) to the androgen receptor of genital skin fibroblasts (GSF) from controls and a subject with familial, receptor‐positive, partial androgen insensitivity. The mutant cells form R1881‐receptor complexes that dissociate 7 times more rapidly than normal at 30°C, and they do not increase their specific R1881‐receptor activity in response to a 72‐hr period of incubation with R1881, whereas the cells from normal individuals do so two‐ to three‐fold. As previously reported [Pinsky et al, 1981; Kaufman et al, 1981], the mutant cells have similar abnormalities with DHT as with R1881. When the patient's cells are incubated for 120 min with varying concentrations (0.05‐3 nM) of R1881 or DHT, Scatchard analysis shows that their androgen‐receptor activity has an apparent equilibrium dissociation constant (Kd) for each ligand that is sixfold greater than that of normal cells (∼0.2 nM). Normal GSF have higher, more variable values of Kd (0.3–1.8 nM) for either ligand after 30 compared to 120 min of incubation, and the 60‐min values are intermediate. This explains why we previously reported that the patient's cells had a 30‐min Kd for DHT in the normal range [Pinsky et al, 1981]. Sucrose gradient centrifugation of mutant GSF cytosol incubated with DHT in the presence of 10 mM sodium molybdate yields a normal 6.5–8S peak of DHT‐receptor complexes.From these data we conclude that (i) normal GSF form initial, low‐affinity androgen‐receptor complexes that are transformed into one (or more) higher affinity (? activated) states by a process that depends on time and initial concentration of androgen; (ii) the subject's GSF can form low‐affinity androgen‐receptor complexes but cannot generate the normal high‐affinity state of the complexes, and this lack precludes augmentation of their androgen‐receptor activity in response to prolonged incubation with either androgen; and (iii) failure of molybdate to stabilize the androgen‐receptor activity in GSF cytosol is not a more sensitive indicator of structurally altered androgen‐receptor proteins than are other qualities described heretofore.
Bone marrow transplantation for severe combined immune deficiency in an infant with chimerism due to intrauterine‐derived maternal lymphocytes: Donor engraftment documented by chromosomal marker studies
Authors: Borzy Michael S. , Magenis Ellen , Tomar Diane 
Published: June 2005

AbstractChromosomal heteromorphisms defined by the quinacrine banding technique were used to identify the maternal origin of 46,XX lymphocytes present in the blood of a male infant with severe combined immune deficiency disease. These chromosomal markers were also used to document the engraftment by donor lymphocytes from the sister and the concurrent disappearance of maternal lymphocytes after a successful bone marrow transplantation. Donor lymphocytes were detected by this technique 6 days after transplantation, earlier than is usually possible with other marker systems and before definite evidence of immunoreconstitution. Maternal lymphocytes persisted in the patient's peripheral blood for a prolonged period of time, being detectable 172 days after transplantation. Analysis of T‐lymphocyte‐and B‐lymphocyte‐enriched populations after transplantation documented lymphoid chimerism with T‐lymphocytes of donor origin and B‐lymphocytes of both patient and donor origin, demonstrating prolonged persistence of patient B‐lymphocytes and suggesting that the patient's immune defect is primarily at the T‐lymphocyte level.
The Meckel syndrome: Clinicopathological findings in 67 patients
Authors: Salonen Riitta , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA nationwide study on the Meckel syndrome (MS) was carried out covering retrospectively the years 1970–1979 and prospectively the years 1980–1981. Sixty‐seven cases from 48 Finnish families were found. The clinical and pathological findings were studied. Cystic dysplasia of the kidneys was present in all the cases where sufficient information was available. In all 41 cases with specimens available from the liver, a typical fibrotic change with proliferation and dilatation of the bile ducts was found. This series and a review of the literature give convincing evidence that cystic dysplasia of the kidneys with fibrosis of the liver is a constant finding in the “true” Meckel syndrome. In conclusion, it is proposed that cystic dysplasia of the kidneys with fibrotic changes of the liver and occipital encephal‐ocele or some other central nervous system malformation are considered as minimal diagnostic criteria of MS. Thus, a histologic investigation of the kidneys and liver is essential in diagnosing MS in doubtful cases. Heterozygote manifestations were not found.
The tricho‐rhino‐phalangeal syndrome(s): Chromosome 8 long arm deletion: Is there a shortest region of overlap between reported cases? TRP I and TRP II syndromes: Are they separate entities?
Authors: Bühler Erica M. , Malik Naseem J. 
Published: June 2005

AbstractCritical cytogenetic (re)evaluation of 2 of our own cases of tricho‐rhino‐phalangeal syndrome II (TRP II), or Langer‐Giedion syndrome (LGS), and 10 cases from the literature, suggests that the shortest region of overlap of the 8q deletion is a part of band q24. 1. This region is assumed to be causally related to this syndrome, and possibly also to TRP I syndrome which, therefore, may not be a causally separate entity.
Segregation analysis in reciprocal translocation carriers
Authors: Petrosky Dorene L. , Borgaonkar D. S. 
Published: June 2005

AbstractSegregation analysis of the offspring of balanced translocation carriers was performed on 327 pedigrees collated from published sources and personal communications. Correction was made for bias of ascertainment. Translocations studied involved chromosome arms 1p, 4q, 6p, 6q, 7p, 8p, 10p, 10q, 11q, 14q, 16q, and 17p. Findings included similar rates of occurrence of abnormal liveborn offspring in male and female carriers except for a reduction of risk in male carriers of translocations segregating by 3:1 mode; an elevated risk of fetal loss (spontaneous abortions and stillbirths) in female carriers of 6q, 11q, and 16q translocations compared to male carriers of these translocations; a fetal loss rate exceeding general population estimates in female carriers of 6q and 10q translocations and in male carriers of 6p, 8p, 10q, and 14q translocations including a rate of nearly 50% among female 6q translocation carriers; a higher than expected number of balanced carriers among liveborn offspring; and a low risk of abnormal liveborn children among carriers ascertained by means other than through unbalanced probands. We propose that some translocation carriers may be helped by consideration of more specific empiric risk figures than have traditionally been used.
Interstitial deletion of chromosome 3p: Report of a patient and delineation of a proximal 3p deletion syndrome
Authors: Neri Giovanni , Reynolds James F. , Westphal Joan , Hinz Jeffrey , Daniel Art 
Published: June 2005

AbstractWe report on a patient with a de novo interstitial deletion of the proximal portion of the short arm of chromosome 3 (p12 → 14.2). The deleted portion excludes the constitutive fragile site assigned to band 3p14. The phenotype of the patient, together with that of three previously reported cases, seems to be sufficiently characteristic to allow the delineation of a proximal 3p deletion syndrome.
The Perlman syndrome: Familial renal dysplasia with Wilms tumor, fetal gigantism and multiple congenital anomalies
Authors: Neri Giovanni , Martini‐Neri Maria Enrica , Katz Ben E. , Opitz John M. 
Published: June 2005

AbstractWe describe a familial syndrome of renal dysplasia, Wilms tumor, hyperplasia of the endocrine pancreas, fetal gigantism, multiple congenital anomalies and mental retardation. This condition was previously described by Perlman et al [1973, 1975] and we propose to call it the “Perlman syndrome.” It appears to be transmitted as an autosomal recessive trait. The possible relationships between dysplasia, neoplasia and malformation are discussed.
A high frequency of structural chromosome abnormalities in a south central texas cytogenetics laboratory
Authors: Young Robert S. , Hansen Kathryn L. , Shapiro Steven D. , Jorgenson Ronald J. 
Published: June 2005

AbstractAbnormalities of chromosome number, such as the autosomal trisomies and sex chromosome aneuploidies, are considered to be sporadic events with low and constant recurrence risk across populations. On the other hand, abnormalities of chromosome structure can be generated by environmental agents and also transmitted in families and therefore may accumulate in certain populations. Evidence from several geographically diverse newborn infant screening studies and from clinical cytogenetics laboratories (including our own) supports the hypothesis that the frequency of structural abnormalities varies among populations, whereas the frequency of numerical abnormalities remains relatively constant among populations. The data from our laboratory, based on 1,201 patients over a 6‐year period, suggest a two‐ to nearly fourfold higher frequency of structural defects over that of other populations (8.8% vs 4.2% and 2.5% of samples tested). Some of the problems associated with making comparisons among the published data sets are discussed, along with alternative explanations for the variability in the frequency of structural defects reported in different populations.
Sensorineural deafness in the FG syndrome: Report on four new cases
Authors: Neri Giovanni , Blumberg Bruce , Miles Paul V. , Opitz John M. 
Published: June 2005

AbstractWe report on four new cases of FG syndrome with typical manifestations of this X‐linked inherited condition and note a hitherto undescribed sign, sensorineural deafness. The association between sensorineural deafness and imperforate anus is likely to represent more than a chance occurrence, given its presence also in the Townes‐Brocks syndrome.
Late‐childhood‐onset spinal muscular atrophy in three Melanesian families in Papua New Guinea
Authors: Scrimgeour Euan M. , Mastaglia Frank L. 
Published: June 2005

AbstractLate‐childhood‐onset spinal muscular atrophy (SMA) with rapid progression from proximal to distal muscle groups and leading to severe incapacity or death in adolescence or early adult life, was studied in two Melanesian families in Papua New Guinea. Probable SMA with cardiomyopathy was observed in a 12‐year‐old boy in a related family. The pattern of inheritance in the study group did not conform to any of the conventional Mendelian modes and it was conjectured that the disease was expressed in heterozygote carriers of the SMA gene only when an allelomorphic activator gene was present.