bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pleiotropy revisited: Molecular explanations of a classic concept
Authors: Pyeritz Reed E. 
Published: June 2005

AbstractAs commonly used, pleiotropy refers to multiple effects on phenotype of a single mutant gene. The importance of this concept to medical genetics has waxed and waned since its formulation soon after the rediscovery of Mendel's laws. Initially, the view that all aspects of a phenotype, and hence all manifestations of a mendelian syndrome, derive from a single function (or dysfunction) of a mutant allele gained ascendancy. Support for the importance of pleiotropy gradually diminished, and reached a low point in the 1940s with the one gene‐one enzyme hypothesis. Studies of mammals and humans with heritable disorders of connective tissue sustained the notion that “genuine” pleiotropy probably did not exist. However, the demise of the relevance of pleiotropy was premature. Detailed understanding of gene organization, expression, and mutation indicates several mechanisms, such as multifunctional proteins, alternative splicing of messenger RNA, and overlapping coding sequences, through which genuine pleiotropy likely occurs in normal development and function, in mendelian syndromes, and in conditions due to somatic mutation. Furthermore, a broad definition of pleiotropy is warranted to subsume syndromes caused by abnormal function of contiguous genes, such as through large deletions, mutation of regulatory elements that coordinate expression, or less clearly understood “position effects.” Thus, the use of pleiotropy in the context of aneuploidy syndromes is not inappropriate.
Characterization of the calcitonin/CGRP gene in Williams syndrome
Authors: Russo Andrew F. , Chamany Katayoun , Klemish Steven W. , Hall Todd M. , Murray Jeffrey C. 
Published: June 2005

AbstractWe have investigated the possibility of mutations in the calcitonin/calcitonin gene related peptide (CGRP) gene in children with Williams syndrome. Involvement of the calcitonin/CGRP gene in Williams syndrome is postulated on the basis that Williams syndrome children often have infantile hypercalcemia and deficient expression of calcitonin, a hormone that lowers serum calcium levels. To test the hypothesis that mutations in the calcitonin/CGRP gene might be responsible for the reduced calcitonin levels, we examined the calcitonin/CGRP gene structure in Williams syndrome children. Analysis of white blood cell DNA by Southern blot hybridizations in 5 individuals did not show any detectable large deletions or rearrangements in the calcitonin/CGRP gene locus. The possibility of small deletions or point mutations within the exon encoding the mature calcitonin hormone is unlikely based on ribonuclease protection assays with patient DNA amplified by the polymerase chain reaction (PCR) technique. These findings suggest that the calcitonin deficiency might be due either to mutations elsewhere in the gene or to defects in the cellular machinery needed for calcitonin synthesis and/or secretion.
Understanding the decision to take the predictive test for Huntington disease
Authors: Meissen Gregory J. , Mastromauro Carol A. , Kiely Dan K. , McNamara Danielle S. , Myers Richard H. 
Published: June 2005

AbstractThe predictive test for Huntington disease (HD) has allowed those at risk to determine gene status prior to symptoms. The purpose of this research was to understand the motivation and the anticipated reactions of those requesting the test. Forty persons at 50% risk for HD and 31 companions participated in a structured personal interview as part of the predictive test protocol. Reasons for taking the test centered on the reduction of anxiety and uncertainty associated with being at risk and enhanced planning and decision making. Participants also believed that taking the test would produce more positive than negative outcomes. With a favorable result, most anticipated a reduction of anxiety, a more normal future, and relief knowing their children would be at a very low risk. Most also cited benefits as more likely than consequences with an unfavorable result. Making the most of life, easier planning, and reduced uncertainty were rated as more likely than any of the adverse impacts, including short‐term depression and becoming frightened. Almost all participants (95%) said they would rather learn that they have the HD gene than remain at 50% risk. The uncertainty, anxiety, and chronic stress associated with being at risk appears to underlie the motivation of many seeking the predictive test for HD.
Molecular analysis of Gaucher disease in a Vietnamese‐Czechoslovak patient with high residual glucocerebrosidase activity
Authors: Choy Francis Y. M. , Woo Mary , Der Kaloustian Vazken M. 
Published: June 2005

AbstractA Vietnamese‐Czechoslovak type 1 Gaucher disease patient with mild hematological complications was found to have approximately 20% of the normal level of fibroblast glucocerebrosidase activity. Using primers that recognize exon 9 sequences of the glucocerebrosidase structural gene absent in the pseudogene, genomic DNA sequences flanking exons 9 and 10 of the glucocerebrosidase structural gene were amplified by the polymerase chain reaction. Allele‐specific oligonucleotide hybridization to amplified genomic DNA sequence of exons 9 and 10 showed an A→G transition in exon 9 that resulted in the 370Ser→370 Asp substitution in one of the alleles. In the other allele, a T→C transition in exon 10 resulted in the 444Leu→444Pro substitution, creating a NciI cleavage site. The heterozygote status of the patient's parents was confirmed biochemically by the detection of intermediate levels (42–55% of normal) of fibroblast glucocerebrosidase activity. Allele‐specific oligonucleotide hybridization to amplified parental genomic DNA showed that the exon 9 mutation was present in the Czechoslovak father, whereas the exon 10 mutation was inherited from the patient's Vietnamese mother. This is the first report of the exon 10 mutation in a person of Vietnamese origin.
Genetic epidemiology of hereditary motor sensory neuropathies (type I)
Authors: Mostacciuolo M. L. , Micaglio G. , Fardin P. , Danieli G. A. 
Published: June 2005

AbstractPatients affected with hereditary motor sensory neuropathy (HMNS) type I were traced through hospital records. Each case was re‐examined, a family history was drawn, and EMG examination was performed in those members of the family who could have inherited the trait. In the prevalence year 1987, in a population of 1,067,130 inhabitants of 2 contiguous provinces of northeast Italy, 100 living cases were recorded in 30 families, giving a minimal prevalence rate estimate of 9.37/100,000. HMSNI is inherited as an autosomal dominant trait, when clinical evaluation includes EMG. No difference may be established clinically between the 2 subtypes (Ia, linked to chromosome 1 and Ib, linked to chromosome 17). Sporadic cases are very rare and the mutation rate, including both the subtypes, is estimated between 3 and 6×10−6.
Renal tubular dysgenesis and very large cranial fontanels in a family with acrocephalosyndactyly S. C. type
Authors: Russo Rosa , D'Armiento Maria , Vecchione Raffaella 
Published: June 2005

AbstractWe describe the first case of renal tubular dysgenesis in a newborn female who survived 15 days. The immunohistochemical and lectin binding studies confirmed the lack of proximal tubule differentiation. Electron microscopy showed undifferentiated tubular epithelium. Widely patent cranial fontanels were present in the proposita. The father and sister showed acrocephalosyndactyly Saethre‐Chotzen type. The parents were not related and there was no familial history of renal pathology.
Short stature, mental retardation, eye anomalies, and cleft lip/palate
Authors: Richieri‐Costa A. , Guion‐Almeida M. L. 
Published: June 2005

AbstractThe syndrome: We describe 3 Brazilian brothers presenting a cluster of signs strongly suggesting a “new” MCA/MR syndrome. The main clinical signs include short stature, microbrachycephaly, mental retardation, palpebral ptosis, coloboma of iris and retina, nystagmus, strabismus, and cleft lip/palate. This is either an autosomal or X‐linked recessive trait.
Amplification of ten deletion‐rich exons of the dystrophin gene by polymerase chain reaction shows deletions in 36 of 90 Japanese families with Duchenne muscular dystrophy
Authors: Kitoh Yoshihiko , Matsuo Masafumi , Nishio Hisahide , Takumi Toru , Nakajima Toshihiro , Masumura Takehiro , Koga Junichi , Nakamura Hajime 
Published: June 2005

AbstractWe analyzed DNA samples taken from 95 Duchenne muscular dystrophy (DMD) patients belonging to 90 different families in Japan using the polymerase chain reaction. Ten different regions at the 5′ end or in the central region of the dystrophin cDNA gene that were previously shown to be prone to deletion were selected for amplification and analysis. Patients in 36 of the 90 families (40%) had deletions in at least one of these segments of the gene. Identical deletions were detected in the dystrophin gene of patients from the same family. The deletions were heterogeneous in size and location. One patient had deletions in 7 of the 10 amplified regions, while 19 patients from 18 families had a deletion in only one of the regions studied. Deletions at the 5′ end were generally larger and more heterogeneous than those in the central region of the gene. One third of deletions had their proximal end breakpoints between exons 44 and 45. This region seems to be particularly vulnerable to gene breakage in DMD patients.
Predictive testing for Huntington disease in Canada: Adverse effects and unexpected results in those receiving a decreased risk
Authors: Huggins Marlene , Bloch Maurice , Wiggins Sandi , Adam Shelin , Suchowersky Oksana , Trew Michael , Klimek Marylou , Greenberg Cheryl R. , Eleff Michael , Thompson Louise P. , Knight Julie , MacLeod Patrick , Girard Kathleen , Theilmann Jane , Hedrick Amy , Hayden Michael R. 
Published: June 2005

AbstractBy January 1, 1991 a total of 388 persons had enrolled in the Canadian collaborative study of predictive testing for Huntington disease (HD). Of these participants, 105 persons have been given a decreased risk result. Contrary to expectations, approximately 10% of persons with a decreased risk result have had psychological difficulties coping with their new status. Here, we describe the individual responses of 6 such persons and experiential themes emerging after following these persons for up to 2 years. Individuals who are more likely to suffer an adverse reaction to a decreased risk result include those persons who have made irreversible decisions based on the belief they would develop HD or those who had unrealistic overoptimistic expectations of the positive effects of a decreased risk result. In contrast to those receiving an increased risk result, the most vulnerable time for persons receiving a decreased risk result is between 2 and 12 months after learning the outcome. The need for assessment and counselling of participants in predictive testing programs, even when there is a decreased risk result, is emphasized.
Cutaneous scar at anterior hair line in mother and child with associated frontal bone defect in child
Authors: Stratis John P. , Ramer Jeanette C. , Manders Ernest K. , Lehman Ralph A. , Ladda Roger L. 
Published: June 2005

AbstractA large frontal bone defect underlying a “V” shaped scar was noted in a newborn male whose mother had an identical “V” shaped scar at the same location in the anterior hairline. Both had hypertelorism and short palpebral fissures. The mother had no radio‐graphic evidence of skull defect and neither mother nor child had other cutaneous or skeletal anomalies. Cranioplasty was performed on the child using the remaining frontal bones with an excellent cosmetic result. Biopsy performed at operation documented scar tissue extending through the dermis and underlain by thickened dura. Mother and child appear to have a variant form of aplasia cutis congenita, an autosomal dominant trait with wide variation in expression. © 1992 Wiley‐Liss, Inc.
Deletions and microdeletions of 22q11.2 in velo‐cardio‐facial syndrome
Authors: Driscoll Deborah A. , Spinner Nancy B. , Budarf Marcia L. , McDonald‐McGinn Donna M. , Zackai Elaine H. , Goldberg Rosalie B. , Shprintzen Robert J. , Saal Howard M. , Zonana Jonathan , Jones Marilyn C. , Mascarello James T. , Emanuel Beverly S. 
Published: June 2005

AbstractVelo‐cardio‐facial syndrome (VCFS), an autosomal dominant disorder, is characterized by cleft palate, cardiac defects, learning disabilities and a typical facial appearance. Less frequently, VCFS patients have manifestations of the DiGeorge complex (DGC) including hypocalcemia, hypoplastic or absent lymphoid tissue and T‐cell deficiency suggesting that these 2 conditions share a common pathogenesis. Here, we report the results of cytogenetic and molecular studies of 15 VCFS patients. High ‐ resolution banding techniques detected an interstitial deletion of 22q11.21‐q11.23 in 3 patients. The remaining 12 patients had apparently normal chromosomes. Molecular analysis with probes from the DiGeorge Chromosome Region (DGCR) within 22q11 detected DNA deletions in 14 of 15 patients. In 2 families, deletions were detected in the affected parent as well as the propositus suggesting that the autosomal dominant transmission of VCFS is due to segregation of a deletion. Deletions of the same loci previously shown to be deleted in patients with DGC explains the overlapping phenotype of VCFS and the DGC and supports the hypothesis that the cause of these two disorders is the same. © 1992 Wiley‐Liss, Inc.
Postaxial acrofacial dysostosis: Report on two patients
Authors: Pereira Sonia C. S. , Rocha Christiane M. G. , Guion‐Almeida M. L. , Richieri‐Costa A. 
Published: June 2005

AbstractWe report on 2 patients with the postaxial acrofacial dysostosis (AFD) syndrome. One patient was an isolated case; the other had an equally affected brother previously described [Richieri‐Costa and Guion‐Almeida, 1989]. Recurrence in sibs suggests autosomal recessive inheritance. © Wiley‐Liss, Inc.
New autosomal recessive syndrome of mental retardation, epilepsy, short stature, and skeletal dysplasia
Authors: Gurrieri F. , Sammito V. , Bellussi A. , Neri G. 
Published: June 2005

AbstractWe describe 4 sibs, 2 males and 2 females, affected with a new autosomal recessive MCA/MR syndrome of short stature, cerebral atrophy, epilepsy, skeletal abnormalities, and moderate to severe mental retardation. © Wiley‐Liss, Inc.
Acrometageria: A spectrum of “premature aging” syndromes
Authors: Greally J. M. , Boone L. Y. , Lenkey S. G. , Wenger S. L. , Steele M. W. 
Published: June 2005

AbstractA child with manifestations of acrogeria and metageria, two “premature aging” syndromes, is presented. Because of his indistinct phenotype and because the question has been previously raised as to whether these conditions are separate, we propose the designation of acrometageria to describe this phenotypic continuum. As there is much in common clinically between acrometageria and the syndrome of type III procollagen deficiency (Ehlers‐Danlos type IV), it might be presumed that a similar pathogenesis for acrometageria exists. This possibility has been tested previously, without demonstrating specific quantitative or qualitative deficits, but with some indirect evidence that collagen metabolism is deranged in these patients. One such crude indicator is the elevation of urinary hyaluronic acid levels, demonstrated in our patient and also observed in the phenotypically distinct Werner and Hutchinson‐Gilford premature aging syndromes. On one hand, it could be argued that this supports the concept that premature aging syndromes exist as a biological continuum. On the other hand, it is equally valid to argue that syndromes of premature aging are so described merely because they include recognizable changes of normal aging and that the demonstration of an underlying mutation in a collagen gene, for example, invalidates their study as models of accelerated normal aging. © Wiley‐Liss, Inc.
Prognosis of prenatally diagnosed children with sex chromosome aneuploidy
Authors: Robinson Arthur , Bender Bruce G. , Linden Mary G. 
Published: June 2005

AbstractSex chromosome aneuploidy (SCA) occurs in about 1/250 amniocenteses, and the significance of the long‐term prognosis of fetuses with SCA is of concern to prospective parents and health care providers. Longitudinal studies in an unselected group of newborn infants with SCA diagnosed postnatally have refuted allegations of mental retardation but have documented an increased risk for developmental problems. Of the 530 phone consultations with parents faced with a prenatal diagnosis of SCA, 68% continued the pregnancy. Twenty of the oldest subsequently born children (now 7–14 years old) were available for follow‐up. In this small sample and age group, the propositi are progressing developmentally at a rate comparable to their sibs and are doing better at school and in peer relations than the SCA group diagnosed postnatally. Only 2 have documented IQs as low as 90. The documented IQs of the remainder, none of whom are sex chromosome mosaics, are all over 110. The parent population in this prenatally diagnosed group is unique and different from that of the postnatally diagnosed group in that over 85% of them are college graduates, often professionals, and upper socioeconomic individuals. The developmental competence of this SCA sample may be attributable to the supportive environment provided by these families, all of whom made a conscious decision to continue the pregnancy. © Wiley‐Liss, Inc.
Commingling and complex segregation analysis of fasting plasma glucose in the lipid research clinics family study
Authors: Rice Treva , Laskarzewski Peter M. , Rao D. C. 
Published: June 2005

AbstractCommingling and segregation patterns of fasting plasma glucose (GL) were examined in family data from 5 clinics (Cincinnati, Stanford, Iowa, Minnesota, and Oklahoma) of the Lipid Research Clinics (LRC) family study. In addition to the primary question of whether there was a major gene for GL, a secondary purpose was to investigate the possibility of genetic heterogeneity among the 5 clinics. No statistical support was found for heterogeneity among clinics, either in the commingling of distributions or in the segregation patterns. For the combined clinics sample, both a major effect and a multifactorial component were significant. However, the major effect (accounting for 73% of the variance) was not found to be consistent with a major gene, as the hypothesis of Mendelian transmission was rejected. The most parsimonious model involved equal transmission probabilities, which suggests that the major effect is not transmitted from parents to offspring. Possible sources of this major non‐Mendelian effect were explored. The multifactorial component accounted for 10% of the variance in GL levels, and no generational differences were noted. Although our study was unable to provide evidence in favor of a major gene effect, it should be noted that a major gene cannot be firmly refuted. For example, a variety of interactions, such as genotype‐dependent age effects, could have masked the transmission probabilities.
Patterns of acrorenal malformation associations
Authors: Evans Jane A. , Vitez Marta , Czeizel Andrew 
Published: June 2005

AbstractLimb and urinary tract defects have frequently been reported to occur together as components of a single acrorenal field defect or in many multiple malformation syndromes. However, the concordance of such anomalies has rarely been studied on a population basis or the relationships between specific limb and renal defects defined. This paper documents the patterns of acrorenal associations seen in over 1,500,000 infants born in Hungary in 1975–1984. In all, 1 in 1,800 infants had a limb deficiency and 9% of these (75 cases) had a urinary tract anomaly. Urinary tract anomalies were most commonly seen with radial ray defects, micromelia and amelia. The commonest recognized patterns were VACTERL association and the cloacal exstrophy and caudal regression sequences. Chromosomal and single gene defects also occurred.Numerical taxonomic techniques delineated six main clusters of patients. Important groupings included micromelia with renal agenesis, split hand/foot with hydronephrosis, and radial ray anomalies with VACTERL defects. The radial ray groups differed in the nature of the VACTERL anomalies seen and with respect to laterality, symmetry, and non‐VACTERL anomalies. There was a strong association of bilateral limb defects with bilateral renal anomalies and unilateral with unilateral. Ipsilateral defects tended to occur in typical VACTERL cases, while contralateral defects tended to occur with additional non VACTERL midline anomalies.Although renal and limb anomalies are associated, in almost all cases malformations in other systems are also present. The precise nature of the malformation patterns seen appear to reflect differences in the nature and magnitude of the underlying dysmorphogenetic processes as well as the timing of their effects. © Wiley‐Liss, Inc.
Trisomy 22 with congenital diaphragmatic hernia and absence of corpus callosum in a liveborn premature infant
Authors: Kim Eun H. , Cohen Ronald S. , Ramachandran Pramela , Mineta Albert K. , Babu V. Ramesh 
Published: June 2005

AbstractWe report on a liveborn premature male with trisomy 22 who had multiple congenital anomalies, including congenital diaphragmatic hernia and absence of corpus callosum. He died of pulmonary hypoplasia associated with diaphragmatic hernia within 12 hours of age. Chromosome analysis by multiple banding techniques based on lymphocyte culture confirmed that he had trisomy 22. This may be the first report of congenital diaphragmatic hernia and isolated absence of corpus callosum associated with trisomy 22. © Wiley‐Liss, Inc.
Molecular detection of a 4p deletion using PCR‐based polymorphisms: A technique for the rapid detection of the Wolf–Hirschhorn syndrome
Authors: Altherr Michael R. , Gusella James F. , Wasmuth John J. , Kummer Mark A. , McKercher Scott W. , Johnson Virginia P. 
Published: June 2005

AbstractWolf–Hirschhorn syndrome (WHS) results from a deletion of part of chromosome 4p. The region of 4p consistently deleted in WHS is near the tip of 4p. Two loci in this region D4S95 and D4S125 are associated with highly informative VNTR polymorphisms and were recently converted to allow PCR‐based screening. PCR analysis was used successfully to identify a small de novo deletion of 4p in a patient suspected of having WHS. This procedure allows a rapid and accurate confirmation of 4p deletions in cases where cytogenetics alone cannot provide a clear answer. © Wiley‐Liss, Inc.
Saethre–Chotzen syndrome with trigonocephaly
Authors: Cristofori Guido , Filippi Giorgio 
Published: June 2005

AbstractWe report on a 20‐month‐old boy with skull malformations and motor delays. A diagnosis of Saethre–Chotzen syndrome was made in view of the clinical and neuroradiological signs. Other unusual findings were trigonocephaly and occipital dysplasia with medial schisis at the foramen occipitalis. The mother showed a mild expression of the syndrome. © 1992 Wiley‐Liss, Inc.
X‐linked recessive inheritance of dysgenesis of corpus callosum in a chinese family
Authors: Kang Wun‐Ming , Huang Chao‐Ching , Lin Shio‐Jean 
Published: June 2005

AbstractThis report describes a new syndrome of dysgenesis of corpus callosum with other anomalies, presenting as microcephaly, mental retardation, spasticity, and unusual facial appearance in 2 Chinese brothers and their maternal cousins. To date, there has not been any case reported in the Chinese population of this syndrome. All 4 patients in this report present with the same unusual face. Hydrocephalus and/or interhemispheric cyst were found among them. This syndrome is transmitted as an X‐linked trait. The nosology is reviewed and discussed. © 1992 Wiley‐Liss, Inc.