bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neither uniparental disomy nor skewed X‐inactivation explains Rett syndrome
Authors: Webb T. , Watkiss E. , Woods C. G. 
Published: July 2010

Webb T, Watkiss E, Woods CG. Neither uniparental disomy nor skewed X‐inactivation explains Rett syndrome.Clin Genet 1993: 44: 236–240. © Munksgaard, 1993The locus DXS255 was studied using the probe M27β in ten probands with Rett syndrome and in eight of their families. No evidence of uniparental disomy of the X chromosome was detected, as all informative probands had inherited an allele from each of their parents. Differential methylation of a CCGG site within the DXS255 locus as shown by digestion with Mspl/Hpall, revealed moderate skewing of X‐inactivation favouring the maternal allele in two of the probands. Random X‐inactivation was present in all mothers tested and in two unaffected sisters. Three of four unaffected siblings had inherited the same maternal allele at DXS255.
Xbal polymorphism in DNA at the apolipoprotein B locus is associated with myocardial infarction (MI)
Authors: Bøhn M. , Bakken A. , Erikssen J. , Berg K. 
Published: July 2010

Bøhn M, Bakken A, Erikssen J, Berg K. Xbal polymorphism in DNA at the apolipoprotein B locus is associated with myocardial infarction (MI).Clin Genet 1993: 44: 241–248. © Munksgaard, 1993High levels of low density lipoprotein (LDL) and its apolipoprotein B (apoB) are risk factors for atherosclerosis and myocardial infarction (MI). There is rich genetic polymorphism in apoB, first detected as the Ag allotypes of LDL, but today mostly examined at the DNA level. Genes contribute to the population variation in LDL and apoB levels and alleles in polymorphisms at the apoB locus are candidate genes with respect to control of lipid levels and susceptibility to atherosclerosis and MI. The Xbal polymorphism at the apoB locus, which involves the third base of threonin codon 2488 (ACC→ACT) without changing the amino acid sequence was examined in a case‐control study comprising 238 survivors of myocardial infarction (MI) and 621 controls. In univariate analysis, frequencies of genotypes in this polymorphism were not statistically different between patients and controls of either sex. However, in multivariate logistic regression analysis, the odds ratio X ‐ X ‐ homozygotes (homozygotes for absence of restriction site) for having MI compared to the pooled group of heterozygotes and X + X + homozygotes (homozygotes for presence of restriction site) was 2.16 (p = 0.007), after adjustments for age, sex, and levels of apoB, high density lipoprotein (HDL) cholesterol (HDLC) and Lp(a) lipoprotein. It appeared that heterozygotes do not have increased risk, compared to the X + X + homozygotes. Stratification according to low or high levels of apoB, HDLC and Lp(a) lipoprotein, showed that the X ‐ X ‐ genotype was more common in patients than controls, in all subgroups. We conclude that the X ‐ allele in double (but not in single) dose most probably increases the risk of MI. The increased risk is apparently not conferred by higher levels of total cholesterol, LDL or apoB, but through some variable or mechanism not closely related to traditional risk factors.
Application of fluorescence in situ hybridization for early prenatal diagnosis of partial trisomy 6p/monosomy 6q due to a familial pericentric inversion
Authors: Wauters J. G. , Bossuyt P. J. , Roelen L. , van Roy B. , Dumon J. 
Published: July 2010

Wauters JG, Bossuyt PJ, Roelen L, van Roy B, Dumon J. Application of fluorescence in situ hybridization for early prenatal diagnosis of partial trisomy 6p/monosomy 6q due to a familial pericentric inversion. Clin Genet 1993: 44: 262–269. © Munksgaard, 1993We report the prenatal diagnosis of a karyotype 46,XY,rec(6)dup p, inv(6) (p23q27) mat detected by fluoroscence in situ hybridization using chromosome 6pter and 6qter specific DNA markers. This partial duplication‐deletion (6p12→pter; 6q27→qter) emanated from a balanced pericentric inversion 46,XX inv(6) (p23q27)pat present in the mother. The phenotypes of two relatives with the same unbalanced anomaly are described. This report illustrates the sensitivity and specificity of fluorescence in situ hybridization (FISH) and its benefit in rapid and unequivocal prenatal diagnosis of subtle chromosomal rearrangements.
Familial syndactyly type III—report of a large pedigree
Authors: McKiernan M. V. , McCann J. J. 
Published: July 2010

McKiernan MV, McCann JJ. Familial syndactyly type III—report of a large pedigree. Clin Genet 1993: 44: 270–271. © Munksgaard, 1993We present a pedigree containing 14 cases of familial syndactyly of the ring and little finger (Type III syndactyly). Three of these were treated surgically in this unit, and a fourth had previously been treated elsewhere by the senior author of this paper. Analysis of the pedigree confirms the autosomal dominant nature of the genetic defect, while clinical study reveals variable phenotypical expression. This is one of the largest pedigrees yet reported for this variety of syndactyly.
Insertion /deletion (I/D) polymorphism at the locus for angiotensin I‐converting enzyme and parental history of myocardial infarction
Authors: Bøhn M. , Berge K. E. , Bakken A. , Erikssen J. , Berg K. 
Published: July 2010

Bøhn M, Berge KE, Bakken A, Erikssen J, Berg K. Insertion/deletion (I/D) polymorphism at the locus for angiotensin I‐converting enzyme and parental history of myocardial infarction.Clin Genet 1993: 44: 298–301. © Munksgaard, 1993One hundred and eighty‐one male and 48 female myocardial infarction (MI) survivors and 172 male and 194 female controls were studied with respect to a possible association between premature parental MI (before age 61 years in mothers and/or before age 56 years in fathers) and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I‐converting enzyme (ACE). In the total series, the frequency of premature parental MI was 14% in the DD (homozygotes for the deletion (D) allele) genotypic group, 10.6% in the ID (heterozygotes) genotypic group and 6.1% in the II (homozygotes for the insertion (I) allele) genotypic group. In all males (male MI survivors and male controls combined), and in the total series, there was a significant excess of DD individuals as compared to II individuals among those with a parental history of premature MI (odds ratio 3.1 (p = 0.03) and 3.1 (p = 0.009), respectively). The ACE polymorphism may be an important genetic marker of MI risk and contribute to clustering of premature MI in families.
Immunofluorescence imaging diagnosis of Fabry heterozygotes using confocal laser scanning microscopy
Authors: Itoh Kohji , Kotani Masaharu , Tai Tadashi , Suzuki Hiroshi , Utsunomiya Toru , Inoue Hisako , Yamada Hideo , Sakuraba Hitoshi , Suzuki Yoshiyuki 
Published: July 2010

Itoh K, Kotani M, Tai T, Suzuki H, Utsunomiya T, Inoue H, Yamada H, Sakuraba H, Suzuki Y. Immunofluorescence imaging diagnosis of Fabry heterozygotes using confocal laser scanning microscopy.Clin Genet 1993: 44: 302–306. © Munksgaard, 1993An immunofluorometric method was developed for the semiquantitative determination of trihexosylceramide in cultured fibroblasts from Fabry disease patients, using a laser scanning confocal imaging system. The accumulated glycolipid was detected as granular inclusions in the cells. Heterozygote identification was achieved both by counting of immunoreactive cells and by measuring the relative fluorescence intensity with a digital imaging system.
Twins and their mildly affected mother with Weaver syndrome
Authors: Dumić M. , Vuković J. , Cvitković M. , Medica I. 
Published: July 2010

Dumić M, Vuković J, Cvitković M, Medica I. Twins and their mildly affected mother with Weaver syndrome. Clin Genet 1993: 44: 338–340. © Munksgaard, 1993A pair of twins, a brother and sister, with the complete form of Weaver syndrome (overgrowth, macrocephaly, facial, skeletal, nail and feet anomalies) and their mildly affected mother are reported, suggesting autosomal dominant inheritance. They all have plantar and palmar hyper‐hydrosis and twins also have nail dysplasia, symptoms which have not yet been described in this syndrome.
Prader‐Willi‐like phenotype in fragile X syndrome
Authors: Schrander‐Stumpel Constance , Gerver Willem‐Jan , Engelen John , Mulder Hans , Fryns Jean‐Pierre 
Published: July 2010

Henk Meyer1A 3‐year‐old boy was referred to the pediatric department because of unexplained extreme obesity. Height and occipitofrontal circumference were just above the 90th centile. Endocrine studies failed to show any significant abnormality. Motor and speech development were generally delayed. On clinical‐cytogenetic‐molecular grounds, Prader‐Willi syndrome was excluded. Fragile X syndrome was diagnosed by the presence of the classical FMR‐1 mutation and confirmed by cytogenetic studies, revealing 20% fragile X positive cells. We compare the clinical features in the present patient with the nine reported patients with fra(X) syndrome and extreme obesity. In pathogenesis, hypothalamic dysregulation is hypothesized. In differential diagnosis of Prader‐Willi syndrome, fragile X has to be considered, especially when laboratory workup for Prader‐Willi syndrome is negative. Clinical behavior can be of help.
Physician knowledge and attitudes towards molecular genetic (DNA) testing of their patients
Authors: Hunter Alasdair , Wright Peter , Cappelli Mario , Kasaboski Ann , Surh Linda 
Published: July 2010

Objective: To better define the knowledge and attitudes of practicing physicians about genetics; specifically molecular genetics. Further, to examine differences between four practice specialties and to assess variables that affect both knowledge and attitudes.Design: A mail‐in survey was sent to a random sample of non‐geneticist physicians, with a second copy sent to non‐responders. Questions included sociodemographic variables, sources of current knowledge and education in genetics, clinical experience with genetic disease, self‐confidence in providing genetic counseling, attitudes towards referring patients to a genetic center, awareness of molecular genetic testing and attitudes towards its use in clinical practice and population screening. Setting. Responses were obtained from over 900 practicing physicians in the Canadian province of Ontario (population 10 million). Genetic services are provided through nine major and several outreach centers. Molecular diagnostic services are provided through six provincially funded laboratories. There are no direct costs to the patient for any genetic service.Participants: A random sample of family physicians, obstetricians, pediatricians and internists was surveyed from both private and hospital based practices.Results and conclusion: Responses varied by specialty, years from graduation, gender, and type of practice. Pediatricians and obstetricians were more knowledgeable about genetics, had more interaction with genetic services and were more supportive of their utility. A major proportion of physicians continue to rely upon undergraduate and medical school courses for knowledge, and the specialties showed different preferences for seeking information. A majority of physicians considered their knowledge of genetics to be adequate, but a minority were confident to provide genetic counseling for simple genetic scenarios. Relatively few had actually made use of DNA diagnostic services and there was relatively poor knowledge of what services were available.
Sclerosteosis: report of a case in a black African man
Authors: Tacconi Paolo , Ferrigno Paola , Cocco Luigi , Carinas Antonino , Tamburini Giorgio , Bergonzi Paolo , Giagheddu Marcello 
Published: July 2010

Sclerosteosis is a rare genetic disorder of bone modelling, similar to, but distinct from, van Buchem disease; it has been described almost exclusively in Afrikaners of South Africa, a white population of Dutch ancestry. Isolated cases have been reported in a girl in Japan, a boy in Spain, and in multiracial families in Brazil and USA.Here we report a case of sclerosteosis in a black man born in Senegal. He presented with the full features of the disease: tall stature; syndactyly; nail dysplasia; massive sclerosis of the long tubular bones, the ribs, the pelvis and the skull; multiple cranial nerve involvement: optic atrophy, facial palsy and trigeminal neuralgia. Radiologic examination, visual and brainstem auditory evoked potentials, computerized tomography and magnetic resonance imaging of the skull were performed. This seems to be the first case of the disease in a black African individual, with no known relationship with Dutch ancestry.
A case of insertional translocation involving chromosomes 2 and 4
Authors: Asamoah Alexander , Nandi Kailas N , Prouty Leonard , Thurmon Theodore F , Chen Harold 
Published: July 2010

We report on a 6‐year‐old Caucasian boy with direct insertion of genetic material from the short arm of chromosome 4 to the short arm of chromosome 2. He was referred for evaluation because of global developmental delay and seizure disorder. A karyotype performed at 41/2 months of age, by a laboratory elsewhere, reportedly showed a deletion of chromosome 4(p12). When we saw him, he had macrocephaly, hypotonia, psychomotor retardation, multiple minor congenital anomalies, and EEG abnormalities. Repeat chromosomes performed by our laboratory revealed that his karyotype was 46, XY, dir ins(2;4)(p24;p15.3p13).Fluorescence in situ hybridization (FISH) analysis, using chromosomes 2 and 4 painting probes confirmed that material from 4p has been translocated to 2p. Also, FISH analysis using the Wolf‐Hirschhorn critical region probe revealed that both loci are intact. Parental chromosomes were normal. This complex rearrangement, though it appears balanced, probably might have resulted in either a structural loss of genetic material or functional loss of a gene action. Thus, his phenotype could be explained by this de novo insertion of chromosome 4 material into chromosome 2. There is no reported case of this specific chromosome rearrangement.
A novel missense mutation (402C → T) in exon 1 in the EDA gene in a family with X‐linked hypohidrotic ectodermal dysplasia
Authors: Hertz Jens Michael , Hansen Karen Nørgaard , Juncker Inger , Kjeldsen Margrethe , Gregersen Niels 
Published: July 2010

Hypohidrotic ectodermal dysplasia (EDA), or Christ‐Siemens‐Touraine syndrome, is clinically characterized by hypohidrosis, hypoodontia and hypotrichosis. The X‐linked form of the disease has been mapped to Xq12‐q13.1, and a gene from this region has recently been cloned. This gene encodes a predicted transmembrane protein of 135 amino acids, which was found to be expressed in keratinocytes, hair follicles, and sweat glands. A variety of rearrangements in this gene have been found in patients with hypohidrotic ectodermal dysplasia.We have screened the probands from nine unrelated Danish families with hypohidrotic ectodermal dysplasia for mutation in exon 1 of the EDA‐gene by polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP). In one large kindred we identified a novel missense mutation (402C → T), which changes a histidine to tyrosine at position 54 in the protein. This mutation cosegregates with the disease in the family and is the first mutation described which affects the predicted transmembrane, hydrophobic domain of the protein.
Genotyping of the polymorphic N‐acetyltransferase (NAT2) and loss of heterozygosity in bladder cancer patients
Authors: Schnakenberg E. , Ehlers Chr , Feyerabend W. , Werdin R. , Hübotter R. , Dreikorn K. , Schloot W. 
Published: July 2010

Acetylation is one of the major routes in metabolism and detoxification of a large number of drugs, chemicals and carcinogens. Slow acetylators are said to be more susceptible to developing bladder cancer and because of investigations about tumor risk based on phenotyping procedures, it was our aim to study the distribution of allelic constellations of the N‐acetyltransferase (NAT2) by genotyping patients with bladder cancer. We analysed NAT2 gene of blood and tumor DNA from 60 patients with primary bladder cancer and DNA of blood samples from 154 healthy individuals. Using ASO‐PCR/RFLP techniques we identified 70% of patients with bladder cancer (n = 42) to be slow acetylators while genotyping of controls resulted in 61% with slow acetylators (n = 94). In addition, dividing bladder cancer patients in males and females the genotype NAT2 * 5B/NAT2 * 6A occured with much higher frequencies in males (OR = 4, 95%; CI = 1.8–8.9).Furthermore, investigating bladder cancer tissues we could detect loss of heterozygosity (LOH) in slow and rapid acetylator genotypes. In eleven out of 60 tumor samples (18.3%) we observed allelic loss at the NAT2 locus while in control DNA of blood from the same patients both alleles were still detectable.
Molecularly proven hypochondroplasia with cloverleaf skull deformity: a novel association
Authors: Angle Brad , Hersh Joseph H , Christensen Katherine M 
Published: July 2010

We report on a case of cloverleaf skull deformity in a patient with hypochondroplasia, a disorder which has not been previously associated with this anomaly. Hypochondroplasia is a bone dysplasia caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Cloverleaf skull is a trilobar skull deformity which is etiologically and genetically heterogeneous and occurs in association with a number of disorders which result from mutations in the fibroblast growth factor receptor genes.Our patient demonstrated one of the common FGFR3 mutations identified in hypochondroplasia, a C‐to‐A change at nucleotide 1620 (C1620A) in the tyrosine kinase domain. The occurrence of a cloverleaf skull deformity appears to represent an example of variable expressivity in hypochondroplasia and suggests that additional factors other than a specific mutation can modify the phenotype in this disorder. In addition, identification of another FGFR mutation associated with cloverleaf skull further illustrates the genetic heterogeneity of this anomaly.
A genetic diagnostic survey in a population of 202 mentally retarded institutionalized patients in the south of Brazil
Authors: Félix Têmis Maria , Leite Júlio César Loguercio , Maluf Sharbel Weidner , Coelho Janice Carneiro 
Published: July 2010

Filix TM, Leite JCL, Maluf SW, Coelho JC. A genetic diagnostic survey in a population of 202 mentally retarded institutionalized patients in the south of Brazil. Clin Genet 1998: 54: 219–223. 0 Munksgaard, 1998The Associaciio dos Pais e Amigos dos Excepciondis (APAE) is an institution for mentally retarded patients located at Caxias do Sul in the south of Brazil. A genetic diagnostic survey of 202 individuals from this institution is presented. The patients had a male:female ratio of 1.3:l and their ages vaned from 1 month to 47 years with a mean of 5.5 years. Using personal and family data, careful clinical examination and laboratory investigation, the authors established a definitive diagnosis in 132 patients (65.34%). A constitutional disorder was present in 111 patients (54.95%). Down's syndrome patients represented 32.15%, while I.98% had other chromosomal anomalies. In 15 patients (12.37%) a disorder of Mendelian inheritance was diagnosed. In 8 patients (3.96%) a multiple congenital anomalies/mental retardation (MCA/MR) syndrome was recorded. Eight patients (3.960/0) had a central nervous system (CNS) malformation. An acquired condition was observed in 21 patients (10.39%), including pre‐ or post‐natal infections. In the remaining 70 patients (34.65%) a conclusive diagnosis was not possible.
Severe mental retardation ‐ distal arthrogryposis in the upper limbs and complex chromosomal rearrangements resulting from a lOq25→qter deletion
Authors: Lukusa T. , Devriendt K. , Holvoet M. , Fryns JP 
Published: July 2010

Lukusa T, Devriendt K, Holvoet M, Fryns JP. Severe mental retardation ‐ distal arthrogryposis in the upper limbs and complex chromosomal rearrangements resulting from a 10q25→qter deletion. CIin Genet 1998: 54: 224–230. 8 Munksgaard, 1998We present the first report of chromosomal rearrangement involving chromosomes 4, 10 and 12. The proband was a 42–year‐old woman with severe mental retardation and multiple congenital anomalies. The most striking physical anomalies were upper limb contractures resulting in distal arthrogryposis. As upper limb flexion contrdctures have been previously reported in individuals with partial distal 1Oq deletion, this sign should be considered as part of the clinical manifestations of 10q25→qter monosomy.
Post‐transplant lymphoproliferative disorder in children: Recent outcomes and response to dual rituximab/low‐dose chemotherapy combination
Authors: Gupta Sushil , Fricker Frederick J. , González‐Peralta Regino P. , Slayton William B. , Schuler Pamela M. , Dharnidharka Vikas R. 
Published: July 2010

Gupta S, Fricker FJ, González‐Peralta RP, Slayton WB, Schuler PM, Dharnidharka VR. Post‐transplant lymphoproliferative disorder in children: Recent outcomes and response to dual rituximab/low‐dose chemotherapy combination. Pediatr Transplantation 2010: 14:896–902. © 2010 John Wiley & Sons A/S.Abstract:  PTLD is a major complication after transplantation. Treatment options for PTLD are not standardized, usually sequential, starting with reduction in immunosuppression. Recently, we have used a dual combination of rituximab and reduced dose chemotherapy (R/C) directly after failed RI. We retrospectively identified 30 pediatric PTLD cases across four organ systems at our center from 1995 to 2008. We assessed recent outcomes of PTLD in children, comparing the responses to different regimens. Two‐yr failure‐free survival was best in renal and heart recipients (80–88%), followed by liver (57%) and lung (0%). Of note, two patients were Epstein–Barr peripheral blood viral load low positive but tumor EBER negative. Three patients had no detectable viral load but were EBER positive. The R/C regimen (n = 8) had the highest CR rate (100%), low recurrence (12%) and lowest mortality (12%). Interferon (n = 4) had 75% CR, 33% recurrence and 25% mortality. Rituximab/prednisone (n = 5) had 80% CR, 50% recurrence and 20% mortality. Other chemotherapy (n = 7, including all 4 T‐cell PTLDs) had 57% CR, 0% recurrence and 14% mortality. Direct dual R/C combination therapy after failed RI is effective and offers another treatment option for B‐cell PTLD.