bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical implications and classification of the constitutive fragile sites
Authors: Daniel Art , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractConstitutive fragile sites (c‐fra) comprise the more prevalent but less recognised suite of fragile sites in eukaryotes. They differ from the heritable (rare) suite of fragile sites (h‐fra) in several significant ways. In the present report, data concerning the c‐fra so far recognised are reviewed in connection with their origin, classification, use as positive controls for cell culture conditions inducing the fra(X), and their presumptive relationships to the characteristic breakpoints in the neoplasias and in constitutional chromosome rearrangements.
Fragile X: Carrier detection in pregnancy
Authors: Tommerup Niels , Holmgren Gösta , Steinbach Peter , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe expression of the fragile X in 9 pregnant women (4 obligate carriers and 5 carriers at risk) was not significantly different from the expression observed either before or after pregnancy in the same individuals. Hence, carrier diagnosis during pregnancy seems to be as reliable as in non‐pregnant women.
Frequency of tri‐ or multiradial configurations in fragile X identification
Authors: Jenkins Edmund C. , Duncan Charlotte J. , Krawczun Michael S. , Berns Lisa M. , Sanz Maureen M. , Brown W. Ted , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractUsing the FUdR system for fragile X induction, we have observed no triradial or bisatellited configurations at fra (X)(q27.3) in over 5,000 fra(X) chromosomes examined from over 150 fra(X) individuals. Based on our observations, and those of Turner and Jacobs (1983) and Daniel et al (1984), we hypothesize that triradial configurations may not occur at Xq27 with FUdR induction. To test this hypothesis we cultured whole blood simultaneously in parallel folate‐deficient and FUdR fra(X) induction systems, and systematically examined fra(X) chromosomes for triradials. Neither autosomes nor X chromosomes exhibited any apparent triradial figures in the FUdR system, while 1.4% of the fra(X) chromsomes in TC 199 exhibited a triradial. Also we observed one autosomal triradial at 4q35. We conclude that triradial configurations, occur in low frequencies in the folate deficient system and seldom if ever in the FUdR system.
Fragile X mental retardation: Prevalence in a group of institutionalized patients in Italy and description of a novel EEG pattern
Authors: Sanfilippo S. , Ragusa R. M. , Musumeci S. , Neri G. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe have studied the prevalence of the fra(X) and of the autosomal fragile sites fra(10) (q25) and fra(16) (q22) in patients from an institute for the mentally retarded in Italy. We found six cases (1.9%) of fra(10) (q25) and 9 (2.9%) of fra(16) (q22). The study of the fra(X) was restricted to a subgroup of 91 males who did not have other chromosome anomalies or variants, and led to the discovery of 4 fra(X) cases. These 4 had the Martin‐Bell syndrome; 3 of them were epileptic and had a characteristic EEG pattern originating during sleep from the temporal lobe not previously described in fra(X) mental retardation.
DNA studies of X‐linked mental retardation associated with a fragile site at Xq27
Authors: Davies Kay E. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractX‐linked mental retardation associated with expression of a fragile site at Xq27.3 has attracted much interest because transmission can occur through phenotypically normal males. Several theories have been proposed to explain the segregation pattern. Linkage analysis in affected families indicates a high frequency of recombination around this site in some families, although in others the genetic relationships are quite different and closer linkage between bridging markers is suggested. The problems associated with the clinical and cytogenetic analyses of this fascinating disorder await the results of detailed molecular approaches.
Inheritance of fragile X syndrome: An hypothesis
Authors: Friedman J. M. , Howard‐Peebles Patricia N. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe fragile X (fra(X), or Martin Bell‐MB) syndrome is considered an X‐linked recessive trait. However, clinically normal male transmitters of the condition have been observed occasionally. The occurrence of “carrier” males and the observation of other unusual genetic characteristics in the MBS suggest that this condition is not a standard X‐linked recessive trait. We propose that the MBS is due to a transposible genetic element which can exist in 3 different chromosomal states and effect 2 different extrachromosomal environments. This model can account for the peculiar genetic behavior of the fragile X syndrome.
Maternal effect on intelligence in fragile X males and females
Authors: van Dyke Daniel L. , Weiss Lester , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIf the mother is the fragile X gene carrier, her daughters (and sons) with the mutation are at high risk of mental retardation. If the father is the (clinically unaffected) carrier, his daughters are normal. This is strong evidence for a maternal effect. The decreased penetrance and variable expressivity in fra(X) offspring of carriers could be related, at least in part, to variabile expression or availability of some meternal factor between pregnancies.We hypothesize a maternal effect in fra(X), with variability in intelligence of heterozygotes and hemizygotes mediated mainly by the maternal uterus or placenta by virtue of different patterns of lyonization in those tissues between pregnancies. If the mother is a carrier, the matenal placenta could develop with a skewed proportion of the normal or the fra(X) genetically active. Each female or male embryo could be exposed to very different enviroments with respect to genetic activity fo the fra(X) chromosome, depending on the site of implantation within the uterus. If the father contributes the fra(X), the intrauterine enviroment is invariably normal and so are the daughters. Modifiers of the intrauterine effect could include lyonzation patterns in tissues of the carrier fetus, and preferential inactivation of the paternal X in extra‐embryonic tissues. The ultimate phenotype of the developing heterozygote and hemizygote may be determined by a threshold effect and interaction between the maternal genotype, the placental genotype, and the fetal genotype. The possibility of maternal effects is testable and has implications for treatment.
Familial Miller‐Dieker syndrome associated with pericentric inversion of chromosome 17
Authors: Greenberg Frank , Stratton Robert F. , Lockhart Lillian H. , Elder Frederick F. B. , Dobyns William B. , Ledbetter David H. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractRecently it has been shown that most cases of the Miller‐Dieker syndrome (MDS) are caused by deletion 17p13.3. All familial cases have been associated with a balanced reciprocal translocation in a carrier parent and unbalanced translocations in their affected offspring. We report a new case of familial MDS in whom the mother carries a pericentric inversion of chromosome 17. She has had two children with MDS, one of whom was shown to carry a recombinant 17 consisting of dup(17q) and del(17p). The high frequency of familial MDS and its consistent association with balanced chromosomal rearrangements in one of the parents makes it important to do high‐resolution chromosome analysis on all patients with MDS and possibly all patients with lissencephaly. Finding a familial balanced rearrangement makes prenatal diagnosis of this condition feasible.
Interstitial deletion of the long arm of chromosome 1 [del(1)(q32q42)]
Authors: Al‐Awadi S. A. , Farag T. I. , Usha R. , El‐Khalifa M. Y. , Sundareshan T. S. , Al‐Othman S. A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA severely malformed girl died 7 days after birth and was found to have de novo interstitial deletion of 1q (1q32 → 1q42). Clinical abnormalities included microcephaly, encephalocele, small eyes with unilateral esotropia, hypertelorism but small prominent nose, highly arched palate, micrognathia, abnormal cry, apparently abnormal low‐set ears, short neck with low posterior hair line, narrow shoulders, congenital heart defect, hypoplastic nails, overlap of toes with flat feet, and single umbilical artery.
Diploid‐triploid mosaicism: Report of necropsy findings
Authors: Pettenati Mark J. , Mirkin L. David , Goldstein David J. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThis is the first report of necropsy findings associated with diploid‐triploid mosaicism. The important pathological findings are presented and compared to those of pure triploidy and those noted in noninvasive studies of diploid‐triploid mosaics. The clinical findings in this patient are compared with those of other reported cases.
Syndrome of short stature, microcephaly, mental retardation, and multiple epiphyseal dysplasia—Lowry‐Wood syndrome
Authors: Nevin Norman C. , Thomas Paul S. , Hutchinson Jill , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe a brother and a sister with a syndrome of short stature, microcephaly, mental retardation, and multiple epiphyseal dysplasia. The parents were normal. This appears to be the second example of the syndrome first described by Lowry and Wood [1975] in two boys who had epiphyseal dysplasia, short stature, microcephaly, and nystagmus; one of these patients was mildly mentally retarded. The Lowry‐Wood syndrome probably is an autosomal recessive trait.
The Wiedemann‐Beckwith syndrome: Pedigree studies on five families with evidence for autosomal dominant inheritance with variable expressivity
Authors: Niikawa Norio , Ishikiriyama Satoshi , Takahashi Satoshi , Inagawa Akira , Tonoki Hidehumi , Ohta Yachio , Hase Naoki , Kamei Tsutomu , Kajii Tadashi , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe 18 individuals from five unrelated families with various manifestations of the Wiedemann‐Beckwith syndrome. Pedigree analysis was performed on the 5 families and on another 19 families in the literature, each of which included more than one affected person. The following findings were obtained: (1) the clinical manifestations among the affected individuals were highly variable—those obvious in infancy tended to become less distinct with increasing age; (2) the syndrome was transmitted directly and vertically through three generations in four families, and through two generations in seven families; (3) male‐to‐male transmission was noted once; (4) the sex ratio in the affected individuals was not significantly different from 1; (5) the segregation ratio of the trait among the sibs of the probands was 0.571 ± 0.066; (6) the affected+carrier/normal ratio was one among the offspring of the affected individuals and obligate carriers; (7) phenotrance (the expected presence of the trait in a generation) of the syndrome in the sibship of probands was complete, whereas that in earlier generations appeared low. The discrepancy is attributable to the lessening of the clinical features with increasing age as well as to a possibly less aggressive search for abnormalities in older generations. These findings indicate that the syndrome is an autosomal dominant trait with variable expressivity.High‐resolution chromosome banding analysis in seven affected individuals and their respective parents showed no abnormalities.
Hexosaminidase A deficiency in adults
Authors: Navon Ruth , Argov Zohar , Frisch Amos , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractDeficiency of hexosaminidase A (Hex A) in adults was found in 15 individuals from nine unrelated Ashkenazi families; 14 individuals had neurological symptoms, one was clinically intact. Clinical, biochemical and genetic findings are reported and compared to previously reported cases.The clinical picture varied between and within families and included spinocerebellar, various motor neuron and cerebellar syndromes. Psychosis appeared in 30% of cases. Involvement of three generations was recorded in one family. The phenotype appears too variable to serve as a basis for genetic classification. The level of Hex A activity in serum, leukocytes, and fibroblasts of all 14 patients was in the range of Tay‐Sachs disease (TSD) homozygotes when measured by the routine heat‐inactivation method. More sensitive and direct methods detected some residual activity. Cultured skin fibroblasts of patients synthesize the α and β chain precursors of Hex A of the same molecular weight as that synthesized by normal fibroblasts. However, the amount of the α chain precursor is greatly reduced. Mature chains were not detected. The one healthy adult we studied displayed a nonuniform distribution of Hex A; while it lacked activity in the serum it had intermediate activity in fibroblasts and leukocytes.
Achondrogenesis II–hypochondrogenesis: Variability versus heterogeneity
Authors: Borochowitz Zvi , Ornoy Asher , Lachman Ralph , Rimoin David L. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractRecently hypochondrogenesis was described as a form of neonatally lethal dwarfism said to resemble spondyloepiphyseal dysplasia congenita radiographically and achondrogenesis II morphologically. Because of the difficulty in distinguishing radiographically between mild achondrogenesis II and severe hypochondrogenesis, we performed a clinical, radiographic, and morphologic study of 24 cases originally classified as either achondrogenesis II or hypochondrogenesis, in an attempt to distinguish between heterogeneity and clinical variability. Review of the radiographic findings in these cases show a fairly continuous spectrum of bony defects, rather than two distinct radiographic syndromes. Chondro‐osseous histology and ultrastructure was similar in all cases regardless of severity and was characterized by hypervascularity and hypercellularity of the cartilage with multiple small, round dilated cysternae of rough endoplasmic reticulum. These findings suggest that hypochondrogenesis and achondrogenesis type II represent a spectrum with marked phenotypic variability.
Lethal multiple pterygium syndrome: Three consecutive cases in one family
Authors: Martin Nicole J. , Hill J. Brian , Cooper David H. , O'Brien Greg D. , Masel John P. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on three sib fetuses with the lethal multiple pterygium syndrome (LMPS), one case occurring in a twin pregnancy. All three fetuses had a cystic hygroma and hydrops was detected by ultrasound. The classification scheme for LMPS proposed by Hall [1984] is examined. With our present state of knowledge of this syndrome, subdivision on bone‐fusion types does not appear to be justified. Antenatal detection by ultrasound is possible in most pregnancies with a second affected fetus because of cystic hygroma and hydrops. In the term or near‐term infant in which ultrasound has not shown cystic hygroma or hydrops, a diagnosis of Pena‐Shokeir type I syndrome should be considered because pterygia are a component of that syndrome but cystic hygroma and hydrops are not.
Another Italian family with mandibuloacral dysplasia: Why does it seem more frequent in Italy?
Authors: Tenconi Romano , Miotti Francesca , Miotti Antonio , Audino Giuliano , Ferro Roberto , Clementi Maurizio , Neri Giovanni 
Published: June 2005

AbstractWe describe three patients (one female and two males in a sibship of 11) with mandibuloacral dysplasia. Only eight families have been reported previously, and of these, four were of Italian origin. The phenotypic spectrum of the condition is delineated and its variability is stressed. The observation of three affected members of both sexes with normal parents supports the hypothesis of autosomal recessive inheritance. The reasons for the high frequency of the condition in Italy are discussed; a local selective advantage for heterozygotes and founder effect might be involved.
Cohabitation, convergence, and environmental covariances
Authors: Lange Kenneth , Reynolds James F. 
Published: June 2005

AbstractTemporal variation in traits has long been a central theme in epidemiology. However, human geneticists have largely avoided this topic. Recently, several authors have shown how temporal variation in relative‐to‐relative covariances can be accommodated within the framework of variance components analysis. The present paper attempts to clarify the mathematics implicit in their approach. A stochastic mechanism is discussed that causes covariances to converge or diverge exponentially fast as relatives cohabit or lead separate lives.
Updating McKusick: An educational exercise for medical students
Authors: Bodurtha Joann N. , Townsend J. Ives , Proud Virginia K. , Nance Walter E. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractAn educational module is described in which first‐year medical students were assigned different entries from the 1983 edition of McKusick's Mendelian Inheritance in Man to revise and update. Following review and discussion in small group sections, the entries were reproduced to provide each student with an updated compendium of the selected genetic disorders. The important principles of Mendelian inheritance could be readily illustrated by the entities assigned to each discussion group. Students learned to use the library and how to understand and integrate clinical and experimental papers. More than half the students reported spending 11–20 h to complete the assignment and reviewed from six to ten articles in detail. The caliber of the entries was found to be significantly correlated with the time students reported they spend on the exercise, but not with the number of papers reviewed, prior knowledge of the disease entity, the frequency of dictionary usage, or undergraduate exposure to genetics.
A computer model for the study of segregation in reciprocal translocation carriers: Application to 20 new cases
Authors: De Arce Miguel A. , Grace Patrick M. , McManus Susan , Neri Giovanni 
Published: June 2005

AbstractWe report on a computer program that, given the breakpoints and the chromosomes involved in a translocation, generates all the possible imbalanced gametes, calculates their corresponding imbalances, and arranges them in order of increasing imbalance. When compared to current, more cumbersome criteria from the literature, both methods agreed on 196 cases of 199 (>98%). When compared to observed data from families with aneuploid offspring, both our program and the other reported methods yield a rate of accurate prediction of 87%. The use of the program is illustrated in 20 new translocations from our laboratory. The possible influence of crossing over in meiosis I in altering the gamete that is most likely to be passed to aneuploid live births is discussed.
Treatment of duchenne muscular dystrophy with growth hormone inhibitors
Authors: Zatz Mayana , Betti Roberto T. B. , Frota‐Pessoa Oswaldo , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA controlled, double‐blind therapeutic trial with the drug mazindol, a growth hormone inhibitor, was performed in a pair of 7 1/2 year‐old monozygotic twins, with Duchenne muscular dystrophy (DMD). The rationable for this trial was based on a patient (reported previously) affected simultaneously with DMD and growth hormone (GH) deficiency, who is showing a benign course of the dystrophic process and is still walking at 18 years.One of the twins received 2 mg of mazindol daily, while the other received a placebo. The assessment, repeated every 2 months, included weight and height measurements, functional and motor ability tests, ergometry and determinations of serum enzymes and GH levels.After one year of trial the code was broken and it was seen that the twin under placebo treatment was strikingly worse than his brother, the progression of whose condition.
Duplication (12q) syndrome in female cousins, resulting from maternal (11;12) (p15.5;q24.2) translocations
Authors: McCorquodale Maureen M. , Rolf Joann , Ruppert Elizabeth S. , Kurczynski Thaddeus W. , Kolacki Paula , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe have studied female cousins with partial duplication of 12q. The cousins' mothers (who are sisters) and the maternal grandmother and great grandmother carried a balanced translocation between chromosomes 11 and 12. We have compared our patients with eight other reported cases of partial duplication of the same chromosome segment (12q24→12qter). Placement of the extra material seems to have little effect on the anomalies present; (only two other cases involved chromosome 11). We propose that our patients provide further evidence that duplication of 12q leads to a clinically identifiable syndrome.
Del(20p) with manifestations of arteriohepatic dysplasia
Authors: Byrne J. L. B. , Harrod M. J. E. , Friedman J. M. , Howard‐Peebles P. N. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA small‐for‐gestational age white female infant was noted to have multiple minor anomalies and severe jejunal stenosis. Mild peripheral pulmonic stenosis, skeletal anomalies, and cholestasis with paucity of intrahepatic bile ducts were observed, and she was diagnosed as having arteriohepatic dysplasia. Chromosome analysis of peripheral blood leukocytes showed a 46,XX,del(20)(p11.2) chromosome constitution.
Association of amyoplasia with gastroschisis, bowel atresia, and defects of the muscular layer of the trunk
Authors: Reid C. O. M. V. , Hall J. G. , Anderson Carol , Bocian Maureen , Carey John , Costa Theresa , Curry Cynthia , Greenberg Frank , Horton William , Jones Marilyn , Lafer Charlotte , Larson Eunice , Lubinsky Mark , McGillivray Barbara , Pembry Marcus , Popkin James , Seller Mary , Siebert Virginia , Verhagen Arie , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe reviewed 225 cases of amyoplasia, and the association of amyoplasia with gastroschisis and with monozygotic twinning was confirmed. In addition, an apparently increased association of bowel atresia and defects in the muscular layer of the trunk wall with amyoplasia was observed. The association of amyoplasia, monozygotic twinning, and these trunk wall defects strongly suggests that the pathogenesis of amyoplasia is linked to some type of vascular compromise.
An apparently new syndrome of microcephalic primordial dwarfism and cataracts
Authors: Toriello Helga V. , Horton William A. , Oostendorp Ann , Waterman Donald F. , Higgins James V. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe two sibs with prenatal‐onset growth deficiency, microcephaly, cataracts, mental retardation, enamel hypoplasia, immune deficiency, and generalized delay of ossification. The combination appears to constitute a previously undescribed autosomal recessive syndrome.