bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable ring chromosome 21: Molecular and clinical definition of the lesion
Authors: Falik‐Borenstein T. C. , Pribyl T. M. , Pulst S. M. , Van Dyke D. L. , Weiss L. , Chu M. L. , Kraus J. , Marshak D. , Korenberg J. R. 
Published: June 2005

AbstractRing chromosome 21 results in deletions of chromosome 21. We report on a cytogenetic and molecular analysis of a 4‐generation family segregating a stable ring chromosome 21 in 4 relatives. To investigate the molecular structure of the ring chromosome, we have analyzed the DNAs of the transmitted ring in a mother and her daughter. The daughter presented at the age of 2 years with severe growth retardation and microcephaly, whereas her mother had microcephaly but normal intelligence. High resolution chromosome analysis of both cases showed the ring chromosome to be r(21)(p13q22) resulting in deletions of 21p and 21q22. The molecular content of the ring chromosome was determined using quantitative Southern blot analyses of 5 random DNA sequences and 4 expressed genes assigned to chromosome 21 and mapping in the region of q22.3. We have shown that collagen type VI, alpha 2 (COL6A2,) S100 protein, beta polypeptide (neural), (S100B), and D21S44 are present in only one copy in both ring carriers, while CRYA1, CBS, D21S43, D21S42, D21S41, and D21S39 are present in two copies. These data and the breakpoints defining the deletion in these patients show that deletion of COL6A2 and S100B is compatible with normal function and confirm the physical map of 21q22.3 by placing COL6A2, S100B, and D21S44 in very distal 21q22.3. Patients with such small deletions provide unique models for understanding the biological and clinical significance of aneuploidy for specific expressed genes.
De Barsy syndrome: Report of a case, literature review, and elastin gene expression studies of the skin
Authors: Karnes P. S. , Shamban A. T. , Olsen D. R. , Fazio M. J. , Falk R. E. 
Published: June 2005

AbstractSeveral “progeroid” syndromes have now been identified. The De Barsy syndrome is an autosomal recessive syndrome of dwarfism, mental deficiency, an “aged” appearance at birth, abnormal elastic fibers on skin biopsy, and lax skin, large helices, eye abnormalities, lax joints, hypotonia, and athetoid posturing. We report one case and review 11 cases from the literature. To understand the abnormal appearance of the elastic fibers on biopsy, we performed elastin gene expression studies on fibroblasts cultured from our patient's skin. Molecular hybridization studies revealed reduced elastin mRNA steady‐state levels as compared with age matched control individuals. Assuming normal rates of mRNA translation, reduced elastin synthesis would occur. Diminished dermal elastin content could explain the altered cutaneous elasticity, decreased elastic fibers in the skin, and many clinical manifestations of individuals with this condition.
45,X/46,X, + r(X) can have a distinct phenotype different from Ullrich‐Turner syndrome
Authors: Grompe M. , Rao N. , Elder F. F. B. , Caskey C. T. , Greenberg F. 
Published: June 2005

AbstractWe present a patient with 45,X/46,X, + r(X) mosaicism and lack of inactivation of either the normal or the ring X in the 46,X, + r(X) cells. The patient has mental retardation, syndactyly, minor facial anomalies, and a congenital heart defect. Although most patients with 45,X/46,X, + r(X) have the Ullrich‐Turner syndrome, 2 previously described patients with this karyotype also had a distinct phenotype consisting of severe mental retardation, syndactyly, and abnormal face. The unusually severe phenotype in these patients was thought to be due to lack of X‐inactivation of the ring X chromosome. The findings in our patient support this hypothesis.
Kenny–Caffey syndrome in two sibs born to consanguineous parents: Evidence for an autosomal recessive variant
Authors: Franceschini P. , Testa A. , Bogetti G. , Girardo E. , Guala A. , Lopez‐Bell G. , Buzio G. , Ferrario E. , Piccato E. 
Published: June 2005

AbstractWe report on 2 sibs with manifestations of the Kenny–Caffey syndrome born to normal, consanguineous parents. Clinical manifestations included dwarfism, internal cortical thickening and medullary stenosis of tubular bones, poorly ossified skull bones, and hypocalcemia. The younger of the two died during a tonic convulsion. The older had neonatal hypoparathyroidism and is now a short intelligent, 1‐year‐old child. This family gives new support to the existence of an autosomal recessive variant of the syndrome.
Use of dystrophin genomic and cDNA probes for solving difficulties in carrier detection and prenatal diagnosis of Duchenne muscular dystrophy
Authors: Shomrat Ruth , Driks Nava , Legum Cyril , Shiloh Yosef 
Published: June 2005

AbstractDuchenne muscular dystrophy (DMD) results from mutations in the X‐linked gene coding for the muscular protein dystrophin. The isolation of genomic and cDNA probes for this gene has greatly facilitated the detection of DMD carriers, which previously relied mainly on measurements of serum creatine kinase (CK), and has enabled prenatal diagnosis of this disease. However, the relatively large size of the gene and the high frequency of recombination and mutation events within the dystrophin locus continue to pose difficulties in the genetic counselling and prenatal diagnosis of DMD, and render the conclusions of molecular analysis less clear cut. This communication presents examples of two such difficulties: the distinction between sporadic and inherited cases in families with a single patient and normal CK levels in all females, and the distinction between mutant and normal dystrophin alleles in families in which the patients have died. The combined use of genomic and cDNA probes allows one to make these distinctions. An additional complicating factor, gonadal mosaicism, is demonstrated.
Pericardial agenesis and focal aplasia cutis in tetrasomy 12p (Pallister‐Killian syndrome)
Authors: Zakowski Maureen F. , Wright Yvonne , Ricci Andrew 
Published: June 2005

AbstractWe report a stillborn female infant with multiple internal and external anatomic abnormalities and mosaicism for isochromosome 12p. These abnormalities included webbed neck, low‐set ears, lower jaw tooth bud, left simian crease, shield chest, focal aplasia cutis, diaphragmatic hernia, hypoplastic lungs, agenesis of pericardium, and Meckel's diverticulum. Karyotypic analysis on cord blood lymphocytes showed 10% mosaicism of 46, XX/47, XX, + i(12p), and analysis of skin fibroblasts showed 50% mosaicism for the same karyotype. The parental karyotypes were normal. There are many reported cases describing the anomalies seen in isochromosome 12p. None of these cases, however, have displayed pericardial agenesis or aplasia cutis. The clinical and cytogenetic features of Pallister‐Killian syndrome are reviewed.
Distal limb deficiency following chorionic villus sampling?
Authors: Schloo Rüdiger , Miny Peter , Holzgreve Wolfgang , Horst Jürgen , Lenz Widukind 
Published: June 2005

AbstractWe have reviewed the follow‐up of almost 3000 completed preganancies in the Münster CVS Program and identified 4 children with distal limb deficiencies. Two cases involved only minor anomalies of distal digital phalanges. One child had a Hanhart anomaly (hypoglossia hypodactylia).We also reviewed 24 cases of limb defects following CVS reported previously. With the exception of a single series, neither the overall incidence of affected children nor cases reported from larger series provide unambiguous evidence of an increased risk of distal limb deficiency caused by CVS.
Growth hormone therapy in achondroplasia
Authors: Horton William A. , Hecht Jacqueline T. , Hood O. Jean , Marshall Robert N. , Moore Wayne V. , Hollowell Joseph G. 
Published: June 2005

AbstractA pilot study was carried out to examine the safety and efficacy of recombinant human growth hormone for growth‐promoting therapy of achondroplasia. The data suggest that the agent in doses used to treat non‐GH‐deficient forms of short stature (0.3 mg/kg/wk) modestly increases overall height velocity in some children with achondroplasia. The effect was seen mainly in children with the lowest growth velocities prior to treatment. No untoward effects were noted. Several questions were raised that require further study.
Ocular albinism in a male with del (6)(q13–q15): Candidate region for autosomal recessive ocular albinism?
Authors: Rose Nancy C. , Menacker Sheryl J. , Schnur Rhonda E. , Jackson Laird , McDonald‐McGinn Donna M. , Stump Tammy , Emanuel Beverly S. , Zackai Elaine H. 
Published: June 2005

AbstractWe describe a boy with an interstitial deletion of 6(q13–q15) and include “coarse” facial features, upslanting palpebral fissures, thin vermilion border of the upper lip, elongated philtrum, developmental delay, and profound hypotonia. The child's eye findings, pedigree, paucity of maternal ocular changes, and lack of melanin macroglobules in the skin suggest that this individual's phenotype is clinically similar to that of autosomal recessive ocular albinism. Though it is possible that this deletion and his ophthalmic disorder are coincidental, we postulate that the ocular albinism may be due to hemizygosity for a paternally derived ocular albinism gene located on chromosome 6 in the region q13–q15.This patient's deletion is secondary to a recombination of a maternal intrachromosomal inverted insertion of this region. Of the 7 reported 6q1 deletions, this is the only case that is due to a familial chromosome rearrangement.
Identification of the origin of ring/marker chromosomes in patients with ullrich‐turner syndrome using X and Y specific alpha satellite DNA probes
Authors: Tharapel Sugandhi A. , Wilroy R. Sid , Keath Amber M. , Rivas Marian L. , Tharapel Avirachan T. 
Published: June 2005

AbstractFluorescent in situ hybridization (FISH) using X and Y chromosome‐specific α satellite DNA probes hybridizing to loci DXZ1 and DYZ3 was performed to identify the origin of ring/marker chromosomes in 6 patients with Ullrich‐Turner syndrome (UTS). All patients had a mosaic karyotype, 5 with 45, X/46,X,r(?) and one with 45,X/46,X,mar. We demonstrated that the marker/ring chromosome in each of these 6 patients originated from the X. A timely knowledge of the X or Y origin of ring and marker chromosomes can be crucial in genetic counseling and medical management since the presence of Y chromosome material in phenotypic females is known to increase the risk for developing gonadoblastoma.
New case of Bartsocas‐Papas syndrome surviving at 20 months
Authors: Giannotti A. , Digilio M. C. , Standoli L. , Zama M. , Dallapiccola B. 
Published: June 2005

AbstractWe report on patient with Bartsocas‐Papas syndrome surviving at age 20 months. Similar to 7 previously reported families, this patient is of Mediterranean ancestry, pointing to clustering of the responsible mutant gene in Southern Europe. In 3 of the 11 Bartsocas‐Papas syndrome patients described so far, including the present case, the condition has not been neonatally lethal. This suggests that about one‐fourth of these patients could survive. This information is important for genetic counseling.
Heterogeneity in ataxia‐telangiectasia: Classical phenotype associated with intermediate cellular radiosensitivity
Authors: Chessa L. , Petrinelli P. , Antonelli A. , Fiorlli M. , Elli R. , Marcucci L. , Federico A. , Gandini E. 
Published: June 2005

AbstractWe identified a subgroup of ataxia‐telangiectasia (AT) patients (2 sibs and 1 unrelated case) characterized by typical clinical manifestations of the disease and cellular radiosensitivity intermediate between classical AT and normal subjects. Our data and a literature review of the intermediate radiosensitivity AT cases show that radioresistant DNA synthesis, cellular radiosensitivity (measured in terms of survival and chromosome break‐age), and the clinical hallmarks behave independently. This raises a number of interesting questions about the correlation between radiobiological and clinical features, and about the nature of the AT gene(s).
Chromosome analysis in spontaneous pregnancy loss: Use of placental villus mesodermal core cell cultures
Authors: Songster Giuliana S. , Sun Li , Chang Shih‐Chung , Cheung Sau W. 
Published: June 2005

AbstractCulture of placental villus mesodermal core cells, a method developed for chorionic villus sampling, was used for cytogenetic analysis in 168 spontaneous pregnancy losses. Successful karyotype results were obtained in 72% of cases and 87.5% of cases in which placental tissue was available. Culture of placental villus mesodermal core cells is useful in the evaluation of spontaneous pregnancy loss, particularly when tissues of direct fetal origin are unavailable or unsuitable for culture. Details of culture and specimen handling techniques are provided.
Possible new type of oral‐facial‐digital syndrome with retinal abnormalities: OFDS type (VIII)
Authors: Gurrieri F. , Sammito V. , Ricci B. , Iossa M. , Bellussi A. , Neri G. 
Published: June 2005

AbstractThe most recent classification of the oral‐facial‐digital syndromes (OFDS) includes 7 types distinguishable by different clinical signs. We describe 2 brothers presenting oral, facial, and digital anomalies and an additional manifestation consisting of specific retinal abnormalities, i.e., retinochoroideal lacunae of colobomatous origin. Our patients may be affected with a new type of OFDS, i.e., OFDS type VIII, characterized by eye abnormalities in addition to other manifestations that partially overlap with those of OFDS type II. Given that there are 2 affected brothers, we cannot distinguish between autosomal and X‐linked recessive inheritance.
Partial gonadal dysgenesis in a patient with a marker Y chromosome
Authors: Fechner Patricia Y. , Smith Kirby D. , Jabs Ethylin Wang , Migeon Claude J. , Berkovitz Gary D. 
Published: June 2005

AbstractWe evaluated a patient with partial gonadal dysgenesis including a right dysgenetic testis and a left streak gonad with rudimentary fallopian tube and uterus. She had ambiguous external genitalia and was raised female. Although her height is normal (25th centile at age 12 years), she has some findings of Ullrich–Turner syndrome. Her karyotype was reported to be 46, X, + marker; subsequent molecular investigations showed the marker to be the short arm of the Y chromosome. Genomic DNA, isolated from leukocytes of the patient and her father, was digested with a variety of restriction endonucleases and subjected to Southern blot analysis. A positive hybridization signal was obtained with probes for the short arm of the Y chromosome (pRsY0.55, SRY, ZFY, 47Z, pY‐190, and YC‐2) in DNA from the patient, indicating the presence of most if not all of the short arm, while long arm probes (HinfA and pY3.4) indicated that at least 75% of the long arm of the Y chromosome was missing. The gene responsible for testicular determination (TDF) is on the distal portion of the short arm of the Y chromosome; Yq has no known influence on sex determination. Hence, the deletion of the long arm of the Y chromosome cannot explain the gonadal dysgenesis in this patient. One explanation for the gonadal dysgenesis and Ullrich–Turner phenotype in the patient could be undetected 45, X/46,X, + marY mosaicism but no such mosaicism was observed in peripheral lymphocytes. Several investigators have suggested the presence of an “anti‐Turner” gene near TDF. Hence it is possible that the clinical phenotype in our patient results from a Y chromosomal defect in sequences flanking TDF, which reduces the function of both TDF and the “anti‐Turner” genes.
Failure of PHA‐stimulated i(12p) lymphocytes to divide in Pallister–Killian syndrome
Authors: Reeser Suzanne L. Thornburg , Wenger Sharon L. 
Published: June 2005

AbstractThe diagnosis of Pallister–Killian syndrome (PKS) is confirmed by tissue‐specific mosaicism of i(12p). The isochromosome is found in skin fibroblasts and bone marrow, but rarely in peripheral lymphocytes. The nature of the isochromosome loss was evaluated using 2 techniques: micronucleus formation for anaphase lag and in situ DNA hybridization for mosaicism in interphase cells. Cells from serial cultured fibroblasts, peripheral blood lymphocytes, and bone marrow from 4 PKS patients were used for the above analysis. Micronucleus formation was similar for PKS and normal diploid cultures, ruling out loss of i(12p) by anaphase lag as the major mechanism of in vitro mosaicism. In situ hybridization using an alpha satellite DNA probe for chromosome 12 was used to examine the presence of the i(12p) in interphase fibroblasts from 1 patient and lymphocytes from 2 patients (age 8 weeks and 1 day). The i(12p) was present in a significantly higher proportion of interphase nuclei in peripheral lymphocytes than in metaphase, suggesting the initial loss of the isochromosome is exaggerated in metaphase by selective division in vitro. In situ hybridization of peripheral lymphocyte interphase cells with chromosome 12 specific probes may be a useful supplemental procedure for the diagnosis of PKS, at least in the newborn infant.
Threshold model in the genetics of age‐dependent disease in twins: I. General principles as applied to Alzheimer disease
Authors: Murphy Edmond A. , Breitner John C. S. 
Published: June 2005

AbstractIn the context of the etiology and pathogenesis of Alzheimer disease (AD), we discuss assumptions under which categorical data on the phenotypes of twin pairs may be used to estimate standardized characteristics (correlation and the critical threshold) for an age‐dependent multinomial process. Important topics include Erlangian, gamma, and Poisson processes, tetrachoric and trichoric functions, and degrees of freedom and how they relate to estimation from both an abstract and a practical standpoint. Under plausible assumptions about the age‐dependence of a heritable trait, it is possible to generate sufficient degrees of freedom to test the genetic model and to explore age‐dependence and the impact of environmental factors that may influence it systematically. Though general in scope, the model is focused on data from twin pairs. The statistical strategy is briefly outlined, but its properties are not examined in detail.
Prenatally detected fragile X females: Long‐term follow‐up studies show high risk of mental impairment
Authors: Brown W. Ted , Jenkins Edmund C. , Goonewardena Ponmani , Miezejeski Charles , Atkin Joan , Devys Didier 
Published: June 2005

AbstractThe prenatal detection of a positive fragile X [fra(X)] female raises difficult counseling issues. In order to address questions regarding the long term outlook, we have conducted follow‐up studies on 4 fra(X) positive females which were carried to term. Three were prenatally detected, and one was a false negative. The subjects were between 3 and 7 years old when follow‐up investigation of mental status was conducted. The first case age, 6 and 9/12 years, had an IQ of 106. On measures of achievement she had some difficulty with arithmetic. The second and third cases were clearly affected. They were judged to be mildly to moderately mentally retarded. The fourth case was borderline normal.The prenatal amniocentesis cytogenetic frequencies had a mean of 3.74% (range 0 ‐ 8.5%). On postnatal follow‐up testing of blood, the mean cytogenetic frequency increased to 31.75% (range 24 ‐ 47%), an 8.5 fold increase.Follow‐up DNA samples from 3 of the 4 subjects were analyzed for underlying DNA mutations using probe StB12.3 which detects insertions and methylation status of the FMR‐1 gene. All 3 showed an affected female genotype with a large insert (>500bp) and complete CpG island methylation.We conclude: (1) prenatally detected cytogenetic frequencies of females increase by an average 8.5 fold on follow‐up postnatal studies, (2) genetic counseling should indicate the risks to be affected are approximately 75% when a positive female is prenatally detected, (3) DNA testing can help determine carrier status but may not accurately predict whether a female will be mentally affected.
Premutation for the martin‐bell syndrome analyzed in a large sardinian family: II. Neuropsychological and behavioral data
Authors: Cianchetti Carlo , Filippi Giorgio , Sannio‐Fancello Giuseppina , Fratta Anna‐Lisa , Marrosu Maria‐Giovanna , Dagna‐Bricarell Franca , Siniscalco Marcello 
Published: June 2005

AbstractWe describe the neuropsychological and behavioral profiles of 48 critical members of a previously reported Sardinian pedigree [Filippi et al., 1991], in which the fully manifested Martin‐Bell syndrome (MBS), observed among males of the latest generations, is clearly the result of step‐wise mutational events occurred repeatedly along the X‐chromosome pathway linking all of them to a common ancestress, who must have been heterozygous for a fragile X (FRAX) premutation. We found that the unquestionable presence in the family of normal transmitting males and females could not be determined on the basis of neuropsychological and behavioral data alone. However, we think that the large variation observed in the expression of most diagnostic parameters among the MBS patients and their close female relatives in this family, could by itself be a connotation of the genome instability which characterizes the FRAX region in pedigrees segregating for the FRAX premutation(s) and mutation(s).
Prenatal detection of Fra(X)(q27.3) in female identical twins: Reliability of low level cytogenetic prenatal expression in females
Authors: Jenkins Edmund C. , Brown W. Ted , Schonberg Steven , Krawczun Michael S. , Goldberg James , Golbus Mitchell S. 
Published: June 2005

AbstractRecently, we detected fra(X)(q27.3) in aminocyte cultures from female identical twins. The pregnant woman did not exhibit fra(X)(q27.3) in whole blood cultures but was the sister of 2 affected brothers. DNA marker analyses showed that she was a carrier of FRAXA. Amniotic fluid cultures (AFCs) from twins A and B exhibited the fragile X [fra(X)] chromosome, but the level of cytogenetic expression was very low in twin A's AFCs. DNA marker studies indicated both twins were carriers of FRAXA. Peripheral umbilical blood sample (PUBS) cultures exhibited fra(X)(q27.3) at a frequency of about 10% for both twins. DNA fingerprinting indicated that the twins were identical, confirming the clinical impression, with a very thin separating amniotic membrane. To our knowledge, this is the only report of prenatal fra(X)(q27.3) detection in female identical twins, and the second report of identical twin detection [Rocchi et al., 1985].We have diagnosed prenatally fra(X)(q27.3) in 5 female fetuses using AFCs. The average fra(X) frequency was 4% for these positive female fetuses with a range of 0.5% to 8.5%. Follow‐up whole blood studies confirmed our original results at an average fra(X) frequency of 25%. In conclusion: 1. Low frequencies, perhaps 1 or 2%, or a few positive cells in AFCs, are likely to increase in magnitude when confirmed in whole blood cultures either pre‐ or postnatally. 2. It appears likely that the risk is low for false positive results in AFCs when low frequencies of fra(X)(q27.3) are encountered.
Intragenic probe used for diagnostics in fragile X families
Authors: Verkerk Annemieke J. M. H. , De Vries Bert B. A. , Niermeijer Martinus F. , Fu Ying‐Hui , Nelson David L. , Warren Stephen T. , Majoor‐Krakauer Danielle F. , Halley Dicky J. J. , Oostra Ben A. 
Published: June 2005

AbstractThe intragenic (FMR‐1) probe pE5.1 was used for DNA analysis in fragile X families. With this probe fragments of altered size can be detected in female carriers, affected individuals and transmitting males. the length of the altered fragments was found to vary from one generation to another as well as between sibs. This instability of the DNA detected by pE5.1 was also seen in peripheral blood within single individuals. These phenomena are illustrated by 4 exemplary families segregating the fragile X syndrome. We demonstrate the diagnostic contribution of intragenic analysis to carrier detection as well as the identification of normal transmitting males carrying premutations. One of the families illustrates the passage of a premutation to a male through 2 generations.