bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new X‐linked dysplasia gigantism syndrome: Follow up in the first family and report on a second Austrian family
Authors: Behmel A. , Plöchl E. , Rosenkranz W. 
Published: June 2005

AbstractWe report on a new X‐linked recessive syndrome in 2 unrelated families, consisting of pre‐ and postnatal growth excess, typical facial phenotype allowing diagnosis at birth, and usually normal physical and intellectual development. The minor anomalies seen at birth include a “coarse” face with wide nasal bridge, short nose with upturned nasal tip, wide open mouth, thick lips, midline depression of the lower lip, enlarged tongue, highly arched palate, large maxilla and jaw, and a short broad neck. Voice is hoarse and affected individuals have a plump, stocky body with pectus excavatum, thoracic scoliosis, hepatosplenomegaly, umbilical and/or inguinal hernias, broad short hands and feet, and in some cases preauricular dimples, abnormal ears, postaxial hexadactyly, hypoplastic index finger nails, and abnormal dermatoglyphics. Early postnatal death is frequent and pathogenetically unexplained. During infancy and childhood the leading manifestations are the overgrowth (>97th centile), striking facial appearance, hypodontia and/or malposition of teeth, genua valga, hypoplastic calf muscles, and clumsiness. Adolescent and adult patients have well proportioned “gigantism” of athletic build (192–210 cm), large “coarse” face, and a deep voice. General intellectual and motor development are either normal or mildly delayed.
Simpson‐Golabi‐Behmel syndrome: An X‐linked encephalo‐trophoschisis syndrome
Authors: Neri G. , Marini R. , Cappa M. , Borrelli P. , Opitz J. M. 
Published: June 2005

AbstractWe report on another family with the so‐called “gigantism‐dysplasia syndrome”, an X‐linked condition characterized by pre‐and postnatal overgrowth, characteristic face with apparent coarseness, dysplastic changes in several tissues, and mild intellectual impairment. This condition has been called the Golabi‐Rosen syndrome; however, we agree that is the same entity as that described, in a milder form, by Simpson et al in 1975 and by Behmel et al in 1984. Therefore, we suggest that this entity be designated the Simpson‐Golabi‐Behmel syndrome. The manifestations in affected individuals suggest that this condition represents an X‐linked encephalo‐tropho‐schisis syndrome.
Fragile X expression in normal and mentally retarded subjects: Effect of treatment with an antifolic agent
Authors: Sanfilippo S. , Ragusa R. M. , Scillato F. , Ruggeri M. , Neri G. 
Published: June 2005

AbstractExpression of the fragile site fra (X) (q27.3) in peripheral lymphocytes was evaluated in mentally retarded patients and in normal control individuals before and after administration of the antifolic agent trimethoprim for 7 days. This treatment was effective in converting the status of some individuals from fra (X)‐negative to fra (X)‐positive. However, the induced level of fra (X) expression was very low and not significantly different in patients and in control subjects and did not increase in those individuals where it was already present before treatment. These data support the contention that fra (X) (q27.3) is a common fragile site and that treatment in vivo with an antifolic agent is not effective in enhancing its degree of expression in vitro. Therefore, such treatment seems to be of no diagnostic value in those cases where the fra (X) syndrome is suspected clinically, but where there is no or very low cytogenetic expression of the fra (X).
A controlled trial of stimulant medication in children with the fragile X syndrome
Authors: Hagerman Randi J. , Murphy Mary A. , Wittenberger Michael D. 
Published: June 2005

AbstractAttentional deficits and hyperactivity frequently are major problems for fra (X) boys. This study evaluated the effectiveness of 2 stimulant medications, methylphenidate and dextroamphetamine compared to placebo in 15 children (13 males, 2 females) with the fra (X) syndrome. A double‐blind crossover design was used with outcome measures which included parent and teacher behavior checklists, a controlled observation period, continuous performance tasks and an actometer measure of movement. When the children were treated with methylphenidate only, improvement was seen in socialization skills and attention span according to teacher checklists. Ten children were clinically considered responders and treatment was continued after the study was completed.
Fra(X) frequency on the active X‐chromosome and phenotype in heterozygous carriers of the fra(X) form of mental retardation
Authors: Wilhelm Dorothea , Froster‐Iskenius Ursula , Paul Jürgen , Schwinger Eberhard 
Published: June 2005

AbstractFemale heterozygotes of the fra(X) form of mental retardation show variable degrees of mental impairment and phenotype expression of the disorder. This might be an effect of inactivation of the X‐chromosome which carries the fra(X)(q). Prior replication studies in heterozygous carriers gave contradictory results with respect to possible genotype‐phenotype correlation. In the interpretation of these studies it is important to understand the effect of BrdU on the fra(X) (q) expression. In a group of 13 hemizygous patients with fra(X) (q) and 7 heterozygous carriers we studied the effect of BrdU on fra(X) expression. In the heterozygous carriers the use of BrdU resulted in a significant suppression of the fra(X) (q), while in hemizygous patients no difference in fra(X) (q) frequency with or without BrdU could be observed. It can be concluded that BrdU suppresses the fra(X) (q) preferentially on the inactive X‐chromosome. Thus the fra(X) (q) frequency on the active X‐chromosome is of primary importance in phenotype correlation studies among heterozygous carriers. In our group of heterozygous carriers we observed a negative correlation between (IQ) phenotype and fra(X) (q) expression on the active X‐chromosome. This suggests that the gene for the fra(X) (q) form of mental retardation is on the X‐chromosome and undergoes inactivation.
Fragile X expression in short‐term whole blood cultures is affected by cell density
Authors: Krawczun Michael S. , Jenkins Edmund C. , Brown W. Ted , Silverman Wayne P. 
Published: June 2005

AbstractThe effect of cell density on expression of the fragile site at (X)(q27.3) in short‐term whole‐blood cultures from patients with fragile X [fra(X)] or Martin‐Bell syndrome was studied. A significant increase in fra(X) frequency was observed in 7 of 8 samples when cell density was decreased. Higher fra(X) frequency was not always noted at below‐routine density, but in some cases fra(X) expression was depressed at above‐routine density. We conclude that decay of the FUdR effect explains the fact that fra(X) expression is affected by culture density. It is significant that a relationship exists between the two; it suggests that in order to maximize fra(X) expression in cases with low‐percentage fra(X) with standard methods, cell density may have to be adjusted. It is possible that in individuals who are normally nonexpressing, such as some obligate female carriers and nonpenetrant males, fra(X) expression may be sensitive to cell density effects.
In situ nick translation of the fragile X region
Authors: Nolin Sarah L. , Jenkins Edmund C. , Brown W. Ted , Dobkin Carl S. 
Published: June 2005

AbstractAt the present time, the molecular nature of the fragile site at Xq27.3 is not well understood. To examine the sensitivity of this region to DNAase I, in situ nick translation was performed on metaphase chromosomes from a fragile X (fra(X)) positive individual. In this technique DNAase I is used to nick regions of chromosomal DNA that are in “open” conformation. Biotinylated dUTP was incorporated by nick translation at these sites. The incorporation was identified by double antibody labeling and avidin‐horseradish peroxidase staining. Spreads, which had been stained with this technique, were photographed and subsequently trysin‐Giemsa G banded (post‐GTG banded) for chromosome identification. In 36 of 44 (82%) fra(X) positive male cells, the region distal to fra(X) (q27.3) was prominently stained in contrast to its light staining appearance in GTG preparations. The fragile site itself was outlined more clearly than can be achieved by GTG or homogeneous staining. When autosomal fragile sites were induced by the addition of 1.5 μM aphidicolin 17 hours prior to harvest, 24 of 27 (89%) fragile sites on the ends of autosomes were prominently stained in regions distal to the break. Because the fra(X) and autosomal fragile regions behaved similarly, this suggests that they have a similar conformation. Thus, while autosomal and Xq27.3 fragile sites are strongly induced by different means, the organization of these sites and the regions distal to them appear to be similar.
A non‐syndromal form of X‐linked mental retardation (XLMR) is linked to DXS14
Authors: Suthers G. K. , Turner G. , Mulley J. C. 
Published: June 2005

AbstractAn analysis of the linkage of a non‐syndromal form of X‐linked mental retardation (MRX1) with a number of markers on the X chromosome was performed in a large pedigree. The affected males had moderate mental retardation; in all other clinical respects and cytogenetically they were normal. No recombinants were observed between the MRX1 gene and the marker DXS14 (p58.1) located at Xpll‐cen (Z (max.) = 2.12 at = 0.00). Recombination was observed between the MRX1 gene and the markers DXS7 and DXYS1 which flank DXS14. This form of XLMR maps to the centromeric portion of the X‐chromosome.
Improved DNA markers for efficient analysis of fragile X families
Authors: Heilig R. , Oberlé I. , Arveiler B. , Hanauer A. , Vidaud M. , Mandel J. L. 
Published: June 2005

AbstractWe report the characteristics of two new probes that detect Bell RFLPs useful for analysis of fragile X families. With these two probes and a single blot, 34% of women are heterozygous both for the proximal marker DXS105 (closer to the fragile X locus than the factor IX gene) and for the distal markers DXS52 or the factor VIII gene. Combined with the analysis of previously described polymorphic markers, it is possible to have a majority of families fully informative for flanking markers using a limited number of probes and restriction digests.
Linkage between the fragile X and F9, DXS52 (St14), DXS98 (4D‐8) and DXS105 (CX55.7)
Authors: Mulley John , Turner Gillian , Bain Sharon , Sutherland Grant R. 
Published: June 2005

AbstractLinkage data using the markersF9,DXS105(cX55.7),DXS98(4D‐8) andDXS52(St14) are presented from 22 kindreds segregating with the fragile X. Two‐point linkage analysis was carried out taking into account cytogenetic results and penetrance classes defined by mental impairment status of mothers. Recombination frequencies (θ) corresponding to the maximum z scores (Ẑ) were obtained betweenF9(Ẑ = 3.48, θ= 0.18),DXS105(Ẑ = 5.06, θ= 0.07),DXS98(Ẑ = 4.79, θ= 0.01) andDXS52(Ẑ = 6.44, θ= 0.09) and the fragile X. Recombination frequencies between marker loci in fragile X families are also presented.These recombination frequencies need to be combined with those from other studies in order to determine the best estimates of map distances for use in genetic counselling, until markers closer to the fragile X, or at the fragile X, can be used. Most potential fra(X) heterozygotes were informative for flanking markers using the above 4 probes. Carrier risks were determined by 3‐point analysis using informative flanking markers, taking into account cytogenetic results. Low level fra(X) expression occurred in 2 probable non‐carriers; emphasising the need for extreme caution in the interpretation of low rates of expression.
Strategy for molecular cloning of the fragile X site DNA
Authors: Warren Stephen T. , Zhang Fuping , Sutcliffe James S. , Peters Jeanne F. 
Published: June 2005

AbstractFragile X syndrome is a common form of mental retardation associated with a fragile site on the human X chromosome. We have recently demonstrated that the fragile X chromosome, when isolated within a somatic cell hybrid, often participates in translocations involving rodent chromosome arms. Cytogenetic and molecular evidence strongly suggests that the human breakpoint of these translocations is within the fragile X sequence. Hence,the joining of heterologous DNA (i.e. from two species) may permit the molecular cloning of the fragile X site. We describe here the cloning approach employed to enhance the isolation of interspecific chromosome translocation junctions. The human portion of the translocation junction should be derived from the fragile X site sequence.
Intercalary heterochromatin of Drosophila as a potential model for human fragile sites
Authors: Laird Charles D. , Lamb Mary M. 
Published: June 2005

AbstractWe summarize our proposal that “intercalary hetero‐chromatin” of Drosophila is a useful model for human fragile sites. Comparison with Drosophila site 11A suggests that the normal allele of fragile site Xq27 is a meiotic pairing site.
Corpus callosum agenesis, facial anomalies, Robin sequence, and other anomalies: A new autosomal recessive syndrome?
Authors: Toriello Helga V. , Carey John C. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe findings in four children, three of whom are sibs, who appear to have the same, previously undescribed multiple congenital anomaly (MCA) syndrome. The main manifestations include agenesis of the corpus callosum, telecanthus, short palpebral fissures, small nose with anteverted nares, Robin sequence, abnormal ears, redundant neck skin, laryngeal anomalies, cardiac defect, short hands, and hypotonia. The presence of this condition in sibs of each sex suggests that autosomal recessive inheritance is the most likely cause.
Amnion rupture sequence in previable fetuses
Authors: Kalousek D. K. , Bamforth S. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractAmnion rupture sequence is considered an uncommon, sporadic condition among liveborn infants. We have examined 1,010 previable fetuses (9–20 weeks developmental age) to determine the incidence and nature of amnion rupture sequence at this stage of development. We found 18 affected fetuses (15 spontaneous and 3 induced abortions.) with the incidence of 1:56. Eleven fetuses had limb constrictions and amputations only; 7 fetuses also had nonlimb involvement, including disruptions of the craniofacial region mimicking encephalocele, unusual facial clefts, and abdominal defects. In 6 pregnancies, constrictions of the umbilical cord by amniotic bands were the cause of fetal intrauterine death.
Congenital adrenal hypoplasia and selective absence of pituitary luteinizing hormone: A new autosomal recessive syndrome
Authors: Burke B. A. , Wick M. R. , King R. , Thompson T. , Hansen J. , Darrae B. T. , Francke U. , Seltzer W. K. , McCabe E. R. B. , Scheithauer B. W. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractCongenital hypoplasia of the adrenal glands (CHA) is a rare conditions, particularly in the absence of a central nervous system (CNS) anomaly. Two major types of CHA have been described in the setting of an apparently normal CNS and pituitary: a cytomegalic type usually with X‐linked recessive inheritance and a miniature adult type that, when hereditary, is an autosomal recessive trait. Glycerol kinase deficiency (GKD) is an X‐linked recessive trait, and it may be associated with CHA and adrenal insufficiency, presumably because of deletion of adjacent X‐linked loci. We report on three sibling infants, one male and two females, with normal CNS and lethal CHA of the miniature adult type, selective absence of pituitary LH; two of the infants also had glycerol kinase (GK) activity that was decreased but not in the GKD range. Restriction fragment length polymorphism (RFLP) analysis of X chromosome markers located at Xp21‐p22 was carried out on the maternal grandfather, both parents, two of three affected infants, and a living normal brother. The results excluded the X‐linked type of this disorder associated with GKD in this family. Autosomal recessive inheritance is most likely.
Congenital scalp defects with distal limb anomalies (Adams‐Oliver syndrome): Report of ten cases and review of the literature
Authors: Küster Wolfgang , Lenz Widukind , Kääriäinen Helena , Majewski Frank , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe one family with 5 affected persons in 4 generations, another family with 2 affected brothers and 3 sporadic cases of the rare syndrome of congenital scalp defects with distal limb deficiency. The manifestations of this syndrome are highly variable. Review of the literature showed 11 families and 19 sporadic cases. In most families the disorder clearly follows an autosomal dominant pattern of inheritance, but in some families with reduced penetrance. Important differential diagnoses are the syndrome of scalp defect and postaxial polydactyly, the syndrome of scalp defect and split‐hand defect, amniotic band sequence, and epidermolysis bullosa dystrophica type Bart.
Familial dilated cardiomyopathy
Authors: Schmidt Michael A. , Michels Virginia V. , Edwards William D. , Miller Fletcher A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIdiopathic dilated cardiomyopathy is generally considered a sporadic, nongenetic disorder, and reports of familial cases are often regarded as rare occurrences. Results of the present investigation of 6 families with this disorder suggest that familial forms of dilated cardiomyopathy occur more frequently than previously suspected. The familial nature of the dilated cardiomyopathy was not readily apparent in 3 of these families until thorough family investigations had been performed. The clinical symptoms and age of onset were variable from one family to another and within families. Based on these observations, it is recommended that all persons diagnosed with dilated cardiomyopathy have a thorough review of their family history. If there are any cases of unexplained heart disease, sudden unexpected death or syncopal episodes, further investigations of relatives should be performed. Echocardiography is a convenient noninvasive tool for investigating relatives. Early diagnosis of affected relatives is important for 2 reasons—treatment of significant arrhythmias may prevent sudden unexpected death, and genetic counseling can be provided.
AFP and age screening for down syndrome
Authors: Wald Nicholas , Cuckle Howard , Opitz John M. , Reynolds James F. , Greenberg Frank 
Published: June 2005

AbstractThe availability of maternal serum alpha‐fetoprotein (AFP) values from neural tube defect screening programmes offers the opportunity to improve the effectiveness of screening for Down syndrome. By appropriately combining information on maternal serum AFP and maternal age fewer women would need an amniocentesis to detect a given number of Down syndrome pregnancies or, for a given number of women having amniocentesis, more cases of Down syndrome would be detected than if age alone were used. For example to detect 40% of pregnancies with Down syndrome using AFP and age, 7% of women would need an amniocentesis compared with 11% using age alone. If an amniocentesis and a chromosome analysis together cost $1,000 this is equivalent to a saving of $37,000 per 1000 women screened. The use of AFP as well as age in Down syndrome screening allows patients to be better informed of their risk of having an affected pregnancy. For example, a 35‐year‐old woman has a risk of a Down syndrome term pregnancy of about 1:380, the risk is 1:120 if the AFP level is 0.40 multiples of the normal median (MoM) and 1:1800 if it is 2.50 MoM. Software providing computer assisted test interpretation has been produced to facilitate the estimation of risk and to identify women with positive screening results.
California's experience with low MS‐AFP results
Authors: Lustig Linda , Clarke Susan , Cunningham George , Schonberg Rhonda , Tompkinson Gwynne , Opitz John M. , Reynolds James F. , Greenberg Frank 
Published: June 2005

AbstractThe California AFP Screening Program was developed to offer pregnant women the opportunity to have their pregnancies screened for open neural tube defects (NTD). Because it is unwise to withhold potentially important clinical information about low MS‐AFP results from the screened women and their physicians, follow‐up diagnostic evaluations and counseling were offered to women with low MS‐AFP results in addition to those with high results or positive family histories of NTD.Between April 7, 1986 and September 30, 1987, over 275,000 women voluntarily participated in the screening program. During the first year of the program 3,939 women were seen for follow‐up evaluations due to low MS‐AFP results. These evaluations occurred at state‐approved AFP follow‐up centers where ultrasonographic dating led to reinterpretation of 35% of the results. Of the remaining 2,552 (65%), 1,940 women (76%) had an amniocentesis. Sixteen Down syndrome fetuses were detected for a yield of 1/121 amniocenteses. Additional chromosome abnormalities included trisomies 18 and 13, Ullrich‐Turner syndrome, (45,X), Klinefelter syndrome (47,XXY) and triploidy. The total yield of significant chromosome abnormalities was 1/78 amniocenteses.
Maternal serum alpha‐fetoprotein screening for down syndrome: Economic considerations
Authors: Swint J. Michael , Greenberg Frank , Opitz John M. , Reynolds James F. , Greenberg Frank 
Published: June 2005

AbstractThe economic consequences of using an index of maternal age and maternal serum alpha‐fetoprotein (MSAFP) screening to indicate risk of Down syndrome (DS) are examined. If DS screening indicated solely by a given maternal age is economically justifiable, then amniocentesis indicated by a DS risk equivalent to that maternal age cutoff, but based on an index of maternal age (for ages below the cutoff) and low MSAFP results, is also economically justifiable. It is concluded that the extant use of MSAFP screening for DS is a move toward the cost‐effective use of scarce resources that can be made available with coordinated planning. However, increased professional and public awareness may result in significant increases in aggregate demand for these services. While MSAFP screening for DS is economically justifiable, there exists some potential for bottlenecks at the aggregate level, and these should be considered in conjunction with recommendations that the technology be adopted on a widespread basis.
Bleeding diathesis in Noonan syndrome: A common association
Authors: Witt David R. , McGillivray Bardbara C. , Allanson Judith E. , Hughes Helen E. , Hathaway William E. , Zipursky Alvin , Hall Judith G. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe Noonan syndrome (NS) is a multiple congenital anomalies (MCA) syndrome with well‐known manifestations. Excessive bleeding has been described occasionally. We report on 19 patients with NS and a bleeding diathesis. Several different defects are identified in the coagulation and platelet systems occurring singly or in combination. Clinical expression is variable. It is concluded that bleeding diatheses occur in NS at a much higher frequency than previously suspected. Consideration is given to possible relationship to underlying metabolic defects which could explain the diverse nature of the bleeding diatheses and also play a role in the pathogenesis of NS. The variety of bleeding diatheses may also reflect heterogeneity within NS.NS patients frequently undergo surgery with increased risk of bleeding. Appropriate evaluation and management is discussed. Evaluation of all NS patients and their families for bleeding disorders should provide important information about the frequency and type of bleeding diatheses which occur and perhaps help to clarify the etiology and pathogenesis of NS.