bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of benefit‐to‐cost analysis to an X‐linked recessive cardiac and humeroperoneal neuromuscular disease
Authors: Wright M. L. , Elsas L. J. 
Published: June 2005

AbstractBenefit‐to‐cost analysis (using standard economic methods) and the predictive tools of genetics are important in the assessment of genetic services for high burden, single gene disorders. We have studied 6 generations of a 167‐member, stable, North Georgia kindred at risk for X‐linked recessive humeroperoneal neuromuscular disease with cardiac conduction defects. This disorder began in affected males in the teen years, with total disability expected by the 3rd decade and death by age 50. Using known fecundity rates and Mendelian probabilities, 26.6 heterozygous females and 9.4 hemizygous affected males were expected in the currently developing generation. We compared the compensatory costs for families with affected males against costs of genetic intervention for this disorder. All costs and benefits were discounted to present values at 6% and 10% and a benefit‐to‐cost ratio was derived. At a 6% discount rate the benefit‐to‐cost ratio was 21 to 1 while at a 10% discount rate the benefit‐to‐cost ratio was 14 to 1.We conclude that although this is an unusual X‐linked muscular dystrophy, it constitutes a prototypic public and private expense which is largely preventable. The method of cost accounting within pedigrees has wide applicability. The results reemphasize the economic benefit of comprehensive public health programs in genetics, particularly in areas with stable, high risk‐populations.
The quantitative genetics of disease: Ambiguities
Authors: Murphy Edmond A. , Optiz John M. 
Published: June 2005

AbstractHere I review briefly some terms appropriate to the formal discussion of the genetics of disease. The motive for writing is that at least three kinds of participating experts are involved: pathologists, geneticists, and statisticians. Not only may some of the terms used in one field be unfamiliar to experts from another, the same term may be used in diverse ways among, or even within, fields. Such ambiguity may create illusory understanding or even frank confusion.
GENFILES: A computerized medical genetics information network. III. CHROMO: The cytogenetics database
Authors: Loughman William D. , Mosher Douglas C. , Epstein Charles J. 
Published: June 2005

AbstractThe computer database CHROMO is the cytogenetic branch of the GENFILES medical genetics information system. Complete cytogenetic laboratory data are maintained in a format that allows detailed searches of client records. Both the standard and extended Paris nomenclature are used.
Partial 3q trisomy due to an unbalanced 3/10 translocation
Authors: Blumberg Bruce , Moore Robin , Mohandas T. , Francke Uta 
Published: June 2005

AbstractA newborn with partial 3q trisomy is reported. This female, small for gestational age, had multiple dysmorphic features, including turricephaly, microcephaly, broad and flat nasal bridge, anteverted nares, small ears, short limbs, bilateral transverse palmar creases, and fifth finger clinodactyly. The patient expired at 20 hours of age. An autopsy demonstrated duplication of the vagina and cervix, a bicornuate uterus, and streak ovaries. Cytogenetic studies revealed the patient to be trisomic for the portion of 3q distal to band 21 [46,XX,‐10,t(3;10) (q21;p15)]. The father was found to carry a balanced 3/10 translocation [46,XY,t(3;10) (q21;p15)].
Site‐specific reciprocal translocation, t(11;22) (q23;q11), in several unrelated families with 3:1 meiotic disjunction
Authors: Zackai Elaine H. , Emanuel Beverly S. , Optiz John M. 
Published: June 2005

AbstractWe have studied 32 unrelated families with a site‐specific reciprocal translocation between chromosomes 11 and 22 [t(11;22) (q23;q11)]. In translocation heterozygotes 3:1 meiotic segregation occurs and results in abnormal progeny who carry the der(22) as a supernumerary chromosome. Phenotypic findings consistent with 47,XX (or XY), +der(22), t(11;22) include mental retardation, preauricular skin tag and/or sinus, ear anomaly, palate anomaly, micrognathia, congenital heart disease, and genital anomalies in males. The frequency of abortions among offspring of male and female heterozygotes is increased. Segregation analysis shows that the risk for unbalanced offspring to be born to female heterozygotes may be as high as 10%, and that there may be a significant risk to male heterozygotes as well. The overall carrier frequency among progeny of 11;22 translocation carriers is 70.6%. The occurrence of multiple 11;22 translocation events is supported by de novo occurrence of the translocation, familial heteromorphic variants of the der(22), and varied racial and ethnic backgrounds of the families. To our knowledge, with the exclusion of centric fusion translocations, this represents the only example of nonrandom exchange in a constitutional chromosomal rearrangement.
Pentasomy X: Report of patient and studies of X‐inactivation
Authors: Funderburk S. J. , Valente M. , Klisak I. , Opitz John M. 
Published: June 2005

AbstractA five‐year‐old girl presented with mental retardation (MR), microcephaly, short stature, ptosis, malocclusion, abnormal elbows, fifth finger clinodactyly, joint hyperextensibility in hands and feet, renal hypoplasia, nonobstructive ureteral stasis, pyelonephritis, and renal failure. Five X chromosomes (49,XXXXX) were found in all peripheral blood lymphocytes and skin fibroblasts examined. Xa RBC typing, utilizing serial dilutions of antiserum, gave agglutination at a higher titer than in either Xg(a+) positive parent; the patient's serum IgM was also elevated. These immunological findings imply a lack of dosage compensation and incomplete inactivation of some X‐linked loci.
A previously unreported, dominantly inherited syndrome of shortness of stature, ear malformations, and hip dislocation: The coxoauricular syndrome—autosomal or X‐linked male‐lethal
Authors: Duca Daniela , Panǎ I. , Ciovirnache Martha , Simionesu Ligia , Ispas I. , Maximilian C. , Opitz John M. 
Published: June 2005

AbstractWe reported an apparently previously undescribed syndrome, designated the coxoauricular syndrome, in a mother and her 3 daughter, all of whom shared in variable manner shortness of stature, minor vertebral and pelvic changes, dislocated hip(s), and microtia with corresponding hearing loss. The oldest daughter had coincidental Ullrich‐Turner syndrome with 46,Xdel(X)(q13) chromosome constitution. Inheritance of the trait in this family is dominant, either autosomal or X‐linked, with hemizygote lethality.
Corneal dermoids and short stature in brother and sister—A new syndrome?
Authors: Guízar‐Vázquez J. , Luengas‐Muñoz F. J. , Antillón F. , Opitz John M. 
Published: June 2005

AbstractWe describe 2 sibs; brother and sister, with corneal dermoids and proportionately short stature. It is suggested that this is an autosomal recessive condition.
Familial midgut anomalies—a spectrum of defects due to the same cause?
Authors: Carmi Rivka , Abeliovich Dvorah , Siplovich Leonardo , Zmora Ehud , Bar‐Ziv Jacob , Opitz John M. 
Published: June 2005

AbstractWe report three familial cases with congenital midgut anomalies: a father and his daughter with congenital midgut volvulus and a consequent intestinal obstruction and father's female sib with atresia of the ascending colon. A common hypothetical cause operating at different gestational periods will be discussed along with the possible genetic implications.
Nonprogressive cerebellar disorder with mental retardation and autosomal recessive inheritance in hutterites
Authors: Schurig Verena , Van Orman Alan , Bowen Peter , Opitz John M. 
Published: June 2005

AbstractWe report a nonprogressive neurological disorder in at least 11 Hutterites with healthy but consanguineous parents. In several of the affected, hypotonia was noted at birth. Retarded motor and mental development became apparent during the first year of life. The age of unsupported walking varied from 5–21 years. Consistent signs were unsteady, broadly based gait and stance, exaggerated deep tendon reflexes mainly in the lower limbs, and mild to moderate mental retardation. Variable signs were extensor plantar reflexes (9/11), short stature (–2SD in 8/11), strabismus (7/11), small muscle mass (6/11), mild intention tremor (3/11), cataracts (1/11), and epilepsy (1/11). CAT scans in two affected sisters showed slight enlargement of the fourth ventricle in one and hypoplasia of the cerebellum in both. The disorder is probably the same as that described earlier under the heading, dysequilibrium syndrome.
Resolution of breakpoints in a complex rearrangement by use of multiple staining techniques: Confirmation of suspected 12p12.3 intraband by deletion dosage effect of LDHB
Authors: Magenis E. , Brown M. G. , Chamberlin J. , Donlon T. , Hepburn D. , Lamvik N. , Lovrien E. , Yoshitomi M. , Opitz John M. 
Published: June 2005

AbstractA complex de novo translocation was found in leukocytes and fibroblasts from a boy with mental retardation and minor abnormalities. The 45,XY chromosome constitution found in all cells was initially interpreted from routine G‐ and Q‐banding techniques as a balanced translocation of part of the short arm of 12 to the short arm of 15 and of the long arm of 21 to the short arm of 12. With additional staining techniques and use of prometaphase chromosome preparations, it was determined that the distal portion of band 12.3 of the short arm of chromosome 12 was missing from the 12/15 and the 12/21 translocation chromosomes. This interpretation was confirmed by a decreased concentration of the LDH‐B subunit in lactate dehydrogenase isozymes of the patient's fibroblasts, consistent with his being hemizygous for the LDHB locus.
Wiedemann‐Beckwith syndrome: Autosomal‐dominant inheritance in a family
Authors: Best Lyle G. , Hoekstra Ronald E. , Opitz John M. 
Published: June 2005

AbstractWe report four additional cases of Wiedemann‐Beckwith syndrome (WBS): A mother, her brother, and two of her children (half‐sibs). Theories of the genetic transmission of the WBS are reviewed. The trait in this family appears to be an autosomal‐dominant with variable expressivity. A theory of delayed mutation of an unstable premutated gene is discussed and an interpretation and observations are offered which could alter slightly the expected pattern of inheritance. Eighty‐eight other family members were screened for evidence of WBS and noteworthy findings are presented.
Differential diagnosis of hydrops fetalis
Authors: Machin G. A. , Opitz John M. 
Published: June 2005

AbstractApart from isoimmunization, a number of conditions may present as hydrops fetalis and now account for a large proportion of hydropic infants. A large differential diagnosis must be considered when investigating the hydropic fetus and placenta while in utero, in the neonatal period, and at autopsy. An investigative protocol is proposed.
Unusual mosaicism of De novo structural abnormalities and ocular anomalies in a male with 13 trisomy syndrome
Authors: Reardon P. C. , Greenstein R. M. , Howard R. O. , Gianacopolos E. K. , Breg W. R. , Opitz John M. 
Published: June 2005

AbstractA boy with the 13 trisomy syndrome was found to have a unique form of mosaicism in which each of the two cell lines had different structural rearrangements. The predominant cell line was partially trisomic for the distal portion of the long arm of chromosome 13, while the minor cell line was trisomic for all of the long arm of 13. The patient is also unusual because he had congenital glaucoma and was still alive at 10 years.
A Study of mitosis, meiosis, histology, and scanning electron microscopic details of spermatogenesis in an infertile male with probable 46,XY/47,XXY germinal mosaicism
Authors: Rajendra Barathur R. , Lee Ming‐liang , Amorosa Louis , Sciorra Leonard J. , Opitz John M. 
Published: June 2005

AbstractA 29‐year‐old infertile man with mild eunuchoid body proportions and unilateral gynecomastia with a low sperm count had normal chromosomes in lymphocytes and skin fibroblasts. Serum testosterone, urinary ketosteroid, and follicle‐stimulating hormone levels were normal, but serum prolactin, luteinizing hormone, and estrogen levels were above normal. Testicular biopsy showed hypocellularity, a pacuity of maturing sperm, and increased lipid content in early spermatogonia. Cytogenetic analysis of the testicular material showed probable 46,XY/47,XXY mosaicism in spermatogonial cells. None of the cells in diakinesis and metaphase I showed the extra‐X as a univalent, and 50% of the cells in diakinesis were hypodiploid with intact XY bivalents. Further analysis of spermatogenesis revealed polymorphic dyads, triads, tetrads, and uncleaved meiotic products of first and second meiosis. Sex chromatin studies of testicular cells showed that 20% of the cells were X‐chromatin positive. Scanning electron microscopic study of sperm revealed a wide range of polymorphisms, with some uncleaved meiotic products maturing into double‐headed and double‐tailed sperm or sperm with bulbous middle pieces or protrusions. A cyto‐genetic basis for the origin of these abnormalities is presented.
A sixth report (eighth case) of craniosynostosis‐radial aplasia (Baller–Gerold) syndrome
Authors: Pelias Mary Z. , Superneau Duane W. , Thurmon Theodore F. , Opitz John M. 
Published: June 2005

AbstractWe report a patient with craniosynostosis, radial aplasia, imperforate anus, and several associated congenital anomalies. It is concluded that she has the Baller‐Gerold syndrome. Parental consanguinity supports the suggestion that this condition is inherited in an autosomal recessive manner.
Genetics of red cell COMT activity: Analysis of thermal stability and family data
Authors: Spielman Richard S. , Weinshilboum Richard M. , Opitz John M. 
Published: June 2005

AbstractPrevious studies have shown that the activity of human red cell catechol‐O‐methyltransferase (RBC COMT) is significantly correlated in sibs, that the population distribution is bimodal, and that RBC COMT from individuals with low activity is more thermolabile than that from individuals with high activity.These observations and additional data from family studies are consistent with the hypothesis that RBC COMT activity is controlled by two alleles at an autosomal locus [Weinshilboum and Raymond, 1977], giving rise to genotypes with different but overlapping activity distributions.In the present study, this hypothesis has been explored with various types of analyses. Given the assumption of Hardy‐Weinberg genotype frequencies, we find that the population distribution of RBC COMT activity is explained much better by codominant or “intermediate” inheritance than by either dominant or recessive inheritance.The intermediate genetic model has also been used to analyze the data of Scanlon et al [1979] on thermal inactivation of RBC COMT in a random sample of blood donors. Hypothesis tests based on this analysis confirm the conclusion of Scanlon et al that individuals with different COMT genotypes differ in the thermostability of their RBC COMT.Using the RBC COMT activities of low‐activity probands and their parents, we have derived the expected distribution of activity among the proband's sibs on the assumption of three genotypes in Hardy‐Weinberg equilibrium in the population. The fit of this expected distribution to that observed is excellent, supporting the genetic model.
Two siblings with unusually mild homozygous β‐thalassemia: A didactic example of the effect of a nonallelic modifier gene on the expressivity of a monogenic disorder
Authors: Prchal Josef , Stamatoyannopoulos G. , Opitz John M. 
Published: June 2005

AbstractTwo adult Black sibs with homozygous β‐thalassemia had severe deficiency of β‐chain production but an unusually mild clinical course and almost normal hematocrit values. Their father had the typical hematological findings of β‐thalassemia trait but the mother, in addition to the β‐thalassemia trait, had elevated F cells (42.2%). Elevated F cells were also present in a hematologically normal sister of the affected providing evidence that a gene for heterocellular hereditary persistence of fetal hemoglobin (HPFH) was also running in this family. The unusually mild clinical course of the two homozygotes is attributed to their inheritance from their mother of the heterocellular HPFH gene. The gene for heterocellular HPFH is nonallelic to the β‐globin locus and apparently acted as a modifier of the homozygous β‐thalassemia phenotype by facilitating F‐cell production and thus diminishing the pathophysiological consequences of the β‐thalassemia defect. The effect of heterocellular HPFH on the expression of homozygous β‐thalassemia or Hb S genotypes is an impressive example of the pathophysiological basis of changes in the expressivity of monogenic disorders due to action of nonallelic modifiers.
Achondrogenesis: A review with special consideration of achondrogenesis type II (langer‐saldino)
Authors: Chen Harold , Liu Charlotte T. , Yang S. Samuel , Opitz John M. 
Published: June 2005

AbstractWe describe two dwarfed infants with large head, short neck and chest, prominent abdomen, and short limbs. Both died neonatally. Radiographic and morphologic characteristics identified the Langer‐Saldino form of achondrogenesis (type II). Review of type II achondrogenesis documented distinctive clinical and anthropometric manifestations (fewer stillbirths, longer survival time and gestational period, larger size of the baby, longer limbs, and characteristic craniofacial features) as compared with type I achondrogenesis (Parenti‐Fraccaro).
dup(4p 15→4pter) in a 19‐year‐old woman resulting from a maternal 4;14 translocation
Authors: Clark Constance E. , Telfer Mary A. , Cowell Henry R. , Kalamchi Ali , Steg Nina L. , Opitz John M. 
Published: June 2005

AbstractWe describe a 19‐year‐old woman who has a duplication of 4p. The karyotype is 46,XX, – 14, + der(14),t(4;14) (p15;p12)mat in lymphocytes and skin fibroblasts. The patient has coarse hair, prominent forehead and tip of nose, coloboma, scoliosis, and mental retardation.
The Weissenbacher–Zweymüller syndrome: Possible neonatal expression of the Stickler syndrome
Authors: Kelly Thaddeus E. , Wells Hugh H. , Tuck Kenneth B. 
Published: June 2005

AbstractThe Robin anomaly is a recognized presenting manifestation of the Stickler syndrome, an autosomal dominantly inherited disorder originally termed “hereditary progressive arthroophthalmopathy.” We report an infant with the Robin anomaly, myopia and dumbbell‐shaped femora and humeri in a family with the Stickler syndrome. This observation suggests that the Weissenbacher‐Zweymüller syndrome is in fact a variant of the Stickler syndrome.
Gastro‐cutaneous syndrome: Peptic ulcer/hiatal hernia, multiple lentigines/café‐aulait spots, hypertelorism, and myopia
Authors: Halal Fahed , Gervais Marc‐H. , Baillargeon Jacques , Lesage Robert , Opitz John M. 
Published: June 2005

AbstractWe report the familial occurrence in a French Canadian family of peptic ulcer/hiatal hernia, multiple lentigines/café‐au‐lait spots, apparent hypertelorism, and myopia caused by a pleiotropic autosomal dominant gene with high penetrance and variable expressivity. Other probable but rarer components of the syndrome include ischemic heart disease, congenital heart disease, and maturity onset diabetes. Symptoms of peptic ulcer/hiatal hernia usually started in the second or third decade and were associated, at least in some examined individuals, with relatively increased acid secretion and abnormal dermatoglyphics.
Brief clinical report and review: The Marden‐Walker syndrome
Authors: Jaatoul Nadia Y. , Haddad Nadra E. , Khoury Leila A. , Afifi Adel K. , Bahuth Nadia B. , Deeb Mary E. , Mikati Mohammad A. , Der Kaloustian Vazken M. 
Published: June 2005

AbstractWe have studied a sibship with one confirmed and three probable cases of the Marden‐Walker syndrome (MWS). Our patient had the major manifestations of blepharophimosis and squint; narrowly arched palate with micrognathia; small mouth and mouth‐breathing; facial deformities and distortions; congenital muscle weakness with resulting scoliosis; mild pectus excavatum; camptodactylies and hip and finger joints subluxation. In addition, he had small, apparently low‐set and slightly malformed auricles with a unilateral preauricular tag. However, he had no apparent renal or cardiovascular involvement.Results of CPK, EMG, and of histochemical, light microscopic, and ultrastructural studies of muscle biopsy do not suggest a primary myopathy but rather CNS related weakness/hypotonia with small muscle mass and hypoactive DTRs. This pathogenetic hypothesis is confirmed by the presence of severe mental retardation and minor brain changes suggesting cortical atrophy. In five previously reported cases there has been microcephaly. Phenotype analysis does not convince that the MWS is a true malformation syndrome, but rather hints at the possibility of a congenital metabolic dysplasia. Genetic analysis demonstrates autosomal‐recessive inheitance in this and two other instances; primarily sporadic occurrence leaves open the possibility of genetic heterogeneity.
Neural tube defects in france: Segregation analysis
Authors: Demenais F. , Le Merrer M. , Briard M. L. , Elston R. C. 
Published: June 2005

AbstractSegregation analysis was performed on a subset of a large body of French data comprising 298 nuclear families. Two models were used in this analysis: the transmission probability model [Elston and Stewart, 1971; Elston, 1981] and the mixed model [Morton and MacLean, 1974]. Both models are consistent with familial aggregation of neural tube defects, in this sample, being due to either the segregation of a recessive major gene or a sibling environmental effect, or both factors. In each case, other environmental factors are also involved. These results were compared to the findings of other studies and discussed in respect to the diversity of the epidemiological features displayed by different populations. Some observations of vertical transmission in a British study and the proportion of affected first cousins, in both France and Great Britain, lead us to reject a possible absence of transmission. We propose a monogenic component with a large influence of environmental factors, some of which may be common to sibs, to explain the occurrence of neural tube defects in this sample.
DNA replication sequence in a dicentric (functionally monocentric) X chromosome formed by the joining of two X chromosomes at region p22
Authors: Yu C. W. , Priest J. H. , Byrd J. R. , Opitz John M. 
Published: June 2005

AbstractIn this study we used densitometry to evaluate DNA replication kinetics in a rearranged chromosome formed by the joining of two X chromosomes at region p22. No 45X mosaicism is present in peripheral blood or fibroblast cultures. The patient has primary amenorrhea, short stature, and gonadal dysgenesis. The sequence of replication in the majority of cells is p11, q11, q13, q22–24, q12, p22, q26, q28, q27, q25, and p21, q21. Thus p11 is the earliest region to replicate, and q21 is the last. In 66% of 127 cells analyzed, the replication pattern is asymmetric, and bands q12, q26, and q28 are most likely to be out of phase on the two sides of the breakpoint. We find that band p22 has a delay of replication compared to an abnormal X derived from two X chromosomes joined at the q23 region previously reported by us. Structural rearrangement may therefore delay replication in the region of the break.