bluuebunny/crossref_metadata_2025 huggingface dataset:
Apolipoproteins B and E, and angiotensin I‐converting enzyme (ACE) genetic polymorphisms in Italian women with coronary artery disease (CAD) and their relationships with plasma lipid and apolipoprotein levels
Authors: Corbo R. M. , Vilardo T. , Mantuano E. , Ruggeri M. , Gemma A. T. , Scacchi R.
Published: July 2010

The XbaI, EcoRI and the signal peptide insertion/deletion (I/D) polymorphic sites of APOB gene, the CfoI polymorphic site of apolipoprotein E gene (APOE), and the insertion/deletion polymorphism of angiotensin I‐converting enzyme (ACE) gene were studied using polymerase chain reaction (PCR) in 55 postmenopausal women with coronary artery disease (CAD) and in 119 control women of equivalent age. Patients and controls were recruited from the population of Rome, considered representative of Central and Southern Italy. There were no significant differences in allele frequencies between the two groups, though APOB X‐, R‐and I, APOE*3, and ACE D alleles were slightly more frequent in the cases than in the controls. The patients did not differ from the controls for plasma total cholesterol (TC), HDL‐cholesterol, LDL‐cholesterol, and apoAI values, while they presented significantly higher levels of triglycerides and apoB, and lower apoE levels. TC, apoE, and apoB quantitative values, adjusted for age, varied significantly among APOB XbaI and APOE genotypes. APOB X‐X‐genotype was associated in patients with a significantly lower mean TC concentration than the other two genotypes pooled together. APOE 3–2 genotype in the controls had significantly lower TC levels with respect to the other two pooled genotypic classes and higher apoE levels compared to 3–3 and 4–3 genotypes. In the patients, 3–2 genotype had significantly lower apoB levels than the pooled 3–3 and 4–3 class. We conclude that in the Italian women the DNA polymorphisms studied in this work do not seem to be important risk factors for CAD occurrence; that apoE quantitation could be another useful parameter to identify subjects at risk of CAD; and that APOB X‐and APOE*2 are the alleles that most influence the interindividual plasma lipid variation among CAD female patients.
Association analysis of TG repeat polymorphism of the neuronal nitric oxide synthase gene with essential hypertension
Authors: Takahashi Y. , Nakayama T. , Soma M. , Uwabo J. , Izumi Y. , Kanmatsuse K.
Published: July 2010

The nitric oxide synthase (NOS) gene is thought to be involved in essential hypertension because nitric oxide is implicated in endothelium‐mediated or nitroxidergic neuron‐mediated vasodilation. Using simple tandem repeat DNA polymorphism of the neuronal constitutive NOS (nNOS) gene, we carried out an association study in patients with essential hypertension. One hundred and thirty‐one patients with essential hypertension and 147 subjects with normal blood pressure were studied. Polymerase chain reaction was applied to amplify the TG repeat site in the nNOS gene, and alleles based on the TG repeat number were determined. Eight alleles were identified in this study of Japanese subjects. Overall distributions of allele frequencies in the two groups were not significantly different. Thus, the genes detected by examination of this microsatellite polymorphism in the nNOS gene are not associated with essential hypertension.
A study of the cognitive and psychological profile in 16 children with congenital or juvenile myotonic dystrophy
Authors: Steyaert J. , Umans S. , Willekens D. , Legius E. , Pijkels E. , de Die‐Smulders C. , Van den Berghe H. , Fryns J‐P.
Published: July 2010

We report data on intelligence and on possibly associated psychopathology in 16 children and adolescents, between 7 and 18 years of age, with congenital or juvenile myotonic dystrophy. We found that all the subjects have an intelligence level below the population mean, four of them in the mentally retarded range. An unexpected number of subjects are in the clinical range on the Child Behavior Checklist. In nine of the 16 subjects, a child psychiatric diagnosis was found using a standardized psychiatric interview. The most frequent child psychiatric diagnosis was Attention Deficit Hyperactivity Disorder.
X‐linked severe mental retardation and a progressive neurological disorder in a Belgian family: clinical and genetic studies
Authors: Claes Stephan , Devriendt Koenraad , D'Adamo Patrizia , Meireleire Jan , Raeymaekers Peter , Toniolo Daniela , Cassiman Jean‐Jacques , Fryns Jean‐Pierre
Published: July 2010

The combination of X‐linked mental retardation (XLMR) and neurological disorders occurs in a number of syndromes. Differential diagnosis mostly depends on clinical data and mapping of responsible genes by linkage analysis. We present a Belgian family with severe XLMR and a progressive neurological disorder with ataxia, spasticity and convulsions. Biochemical investigations, neuroimaging and neuropathology were normal. Linkage analysis pointed to region Xq27–28 as the probable locus for the genetic defect. The sequence of the LI CAM cDNA, a possible candidate gene, proved to be normal in the patients. This suggests the presence of a genetic factor on Xq27–28, different from LI CAM, which can lead to severe XLMR and a progressive neurological disorder.
Factor V Leiden (R506Q) and risk of venous thromboembolism: a case‐control study based on the Spanish population
Authors: García‐Gala José M. , Alvarez Victoria , Pinto Carmen R. , Soto Inmaculada , Urgellés Manuel F. , Menéndez María J. , Carracedo Carmen , López‐Larrea Carlos , Coto Eliecer
Published: July 2010

Resistance to activated protein C (APC) is a frequent cause of thrombophilia. Most patients showing APC‐resistance have a G to A mutation at codon 506 of the factor V that converts arginine to glutamine. This mutation is present in populations worldwide with frequencies ranging from 0.01 to 0.05. Genotyping of 150 control individuals from the Spanish population showed that 3.33% of them carried the mutation. Several studies have measured resistance to APC (following a classical functional assay) and have determined the factor V genotype in a number of thrombophilic patients, in an attempt to compare the predictive vaiue of both laboratory methods. To assess the incidence of the factor V mutation among Spanish thrombophilic patients, we genotyped 51 of these. The frequency of mutation carriers rose from 3.33% in the controls to 53% in the patients. We found significant differences for the thrombosis‐free survival curves and for the age at the first thrombotic event between patients who carried or did not carry the mutation. Analysis of relatives of 16 patients who carried the factor V mutation suggests the existence of additional genes that modulate the effect of the factor V gene in the development of venous thrombosis among carriers of the G to A mutation.
Oculocerebrocutaneous syndrome: report of three additional cases and aetiological considerations
Authors: Moog U. , de Die‐Smulders C. , Systermans J. M. J. , Cobben J. M.
Published: July 2010

The oculocerebrocutaneous (OCC) syndrome is characterized by the presence of orbital cysts and microphthalmia/anophthalmia, focal hypo‐and aplastic skin defects, skin appendages and cerebral malformations. Most of the patients suffer from psychomotor retardation and seizures. To date, 23 patients in total have been reported. We report on three additional cases which illustrate the broad clinical spectrum of this disorder. In one case, the differentiation between OCC syndrome and encephalocraniocutaneous lipomatosis was difficult. A brief review of the clinical features of OCC syndrome is given. Possible aetiological hypotheses are discussed, namely survival of a lethal mutation by mosaicism, an autosomal dominant mutation and external causal factors. Disruption of the anterior neuroectodermal plate seems to be the most probable pathogenic mechanism.
Is the frequency of Robinow syndrome relatively high in Turkey? Four more case reports
Authors: Akçit Sadik , Aydinlioǧlu Haul , Dizdarer Gülşen , Çaǧlayan Suat , Bektaşlar Dilber , Cin Ayşe
Published: July 2010

We describe the clinical features of Robinow syndrome in the children of four Turkish couples. All the patients had cardinal features of this condition, such as short stature, frontal bossing, hypertelorism, short upturned nose with anteverted nares, micrognathia, mesomelic shortening of the forearms, vertebral and costal anomalies and hypoplastic genitalia. In contrast to reports in the literature, one patient showed extensive webbing of the toes and epigastric hernia. Parental consanguinity was present in two of the four cases. To our knowledge, at least 80 cases have been reported in the literature to date, including 19 cases born to Turkish couples in addition to our four cases. The evidence suggests that the frequency of Robinow syndrome is relatively higher in Turkey than in other areas of the world.
Del (X)(p21.2) in a mother and two daughters with variable ovarian function
Authors: Zinn Andrew R. , Ouyang Bing , Ross Judith L. , Varma Surendra , Bourgeois Michael , Tonk Vijay
Published: July 2010

We report a family in which a woman with the mosaic karyotype 45,X/46,X,del(X)(p21.2) transmitted the deleted X chromosome to two daughters. The nature of the deletion was confirmed by fluorescent in situ hybridization (FISH). All three family members showed somatic Ullrich‐Turner syndrome features, but only one daughter had ovarian failure. These observations have implications for the diagnosis of Ullrich‐Turner syndrome and genotype/phenotype correlations of X chromosome deletions.
Detection of 100% of the CFTR mutations in 63 CF families from Tyrol
Authors: Stuhrmann M. , Dörk T. , Frühwirth M. , Golla A. , Skawran B. , Antonin W. , Ebhardt M. , Loos A. , Ellemunter H. , Schmidtke J.
Published: July 2010

We identified 100% of the CFTR gene mutations, including three novel mutations, in 126 unrelated cystic fibrosis chromosomes from Tyrol, Austria. The frequency of the major mutation ΔF508 (74.6%) was not significantly different in Tyrolian CF‐patients than in patients from Bavaria (71.0%) and Middle‐and Northern Germany (71.9%), but was significantly higher than in patients from Styria (58.1%) or Northern Italy (47.6%). Interestingly, the distribution of the next most frequent mutations, R1162X (8.7%) 2183AA→G, 2789 +5G→A and G542X (2.4% each), was more similar to the distribution of these mutations among CF‐patients from Northern Italy than to those from Styria, Bavaria or Middle‐and Northern Germany. Nine further mutations occurred once or twice. One of these, the missense mutation M1101K, is rare worldwide but very frequent in the Hutterite brethren, a small founder population which came from Southern Austria to Northern America. Three other different mutations (ΔL453, 1874insT and 4108delT) were present in single Tyrolian families and have not been described before. The identification of 100% of CFTR gene mutations in a particular CF population demonstrates the power of genetic analysis for the diagnosis and counselling of CF families in this restricted geographical area of Austria. Our study provides evidence for a closer genetic relation between CF patients from Tyrol and those from Bavaria or Middle‐and Northern Germany as well as Northern Italy, than between CF patients from the two Austrian states Tyrol and Styria.
Discordance between malignant hyperthermia susceptibility and RYR1 mutation C1840T in two Scandinavian MH families exhibiting this mutation
Authors: Fagerlund T. H. , Ørding H. , Bendixen D. , Islander G. , Twetman E. Ranklev , Berg K.
Published: July 2010

The ryanodine receptor 1 (RYR1) mutation C1840T has been reported to segregate with malignant hyperthermia (MH) susceptibility in several families. We have investigated several Scandinavian MH families with respect to five different RYR1 mutations reported to cause predisposition to MH, and we here report on two of the families in which the C1840T mutation was detected. In these two families there was recombination between MH susceptibility and this mutation in one and three individuals, respectively. These findings may suggest that it is necessary to reconsider the specificity of the IVCT and the role of C1840T as a cause of MH susceptibility in some families exhibiting this mutation.
Genetic analysis of adult‐onset cataract in a city‐based ophthalmic hospital
Authors: Vijaya Ramachandran , Gupta Rajkumar , Panda Gautam , Ravishankar Krishnamoorthy , Kumaramanickavel Govindasamy
Published: July 2010

Adult‐onset cataract (AOC) is a major ocular health problem and is the number one cause of blindness in the world. It is interesting to note that if the development of cataract is delayed by 10 years, the number of cataract surgeries needed would decrease by 45%. To prevent or delay cataract, the molecular pathological mechanisms underlying the lens change have to be understood, and this requires that the genes involved in such mechanisms should be identified. Hence, in this study we aim to identify AOC families which show a clear mendelian inheritance pattern, as only these families would be ideal for mapping the genes responsible. Over a period of 8 months, from September 1995—April 1996, 17 families with two or more affected members were identified. Segregation analysis showed autosomal dominant inheritance in multiple affected families. We propose to map the genes responsible for cataract in these families by linkage analysis and mutational screening of candidate genes.
Mosaicism for a small supernumerary ring X chromosome in a dysmorphic, growth‐retarded male: mos47,XXY/48,XXY, + r(X)
Authors: Manea Susan R. , Gershin Irina F. , Babu Arvind , Willner Judith P. , Desnick Robert J. , Cotter Philip D.
Published: July 2010

Supernumerary ring X [r(X)] chromosomes are often found in patients with Turner syndrome. The phenotypic effects of the r(X) chromosome are variable, and largely depend on the presence or absence of the X inactivation (XIST) locus. Ring(X) chromosomes in males are rare and have been previously reported in only four cases, with 47,XY, + r(X) or mos47,XY, + r(X)/46,XY karyotypes. These patients all had developmental delay and dysmorphic features. We describe a 2.5‐year‐old male patient with facial dysmorphia, growth retardation, microcephaly, global developmental delay, and microphallus. Cytogenetic analysis from peripheral blood lymphocytes and fibroblasts identified mosaicism for two cell lines: mos48,XXY, + r(?X)/47,XXY. Fluorescence in situ hybridization (FISH) with an X chromosome paint showed the ring chromosome to be X chromosome derived. This is the first case of an r(X) chromosome described in a 47,XXY patient. FISH analysis of the r(X) chromosome with an XIST probe showed that the XIST locus was absent. Functional disomy of genes in the r(X) chromosome most likely accounts for the abnormal phenotype in the proband.
Variant euchromatic band within 16q12.1
Authors: Verma Ram S. , Kleyman Svetlana M. , Conte Robert A.
Published: July 2010

The enlarged short arm of chromosome 16 resulting in an additional euchromatic band has been regarded as a variant. We present an unreported case with an unusual variant of chromosome 16, where the mother and daughter both have an additional band (q 12.1) in the long arm. Its origin is chromosome 16, as revealed by FISH‐technique, and its familial nature suggests that it has no clinical significance.
Lp(a) lipoprotein is a major risk factor for cardiovascular disease: pathogenic mechanisms and clinical significance
Authors: Dahlén Gösta H. , Stenlund Hans
Published: July 2010

The results of two previous and two recent studies of middle‐aged males and females are presented to exemplify the clinical importance of lipoprotein (a) (Lp(a)) as a risk factor for atherosclerosis and coronary heart disease. In these studies various conventional and recently suggested risk factors were included and different methods for Lp(a) quantification were used. Lp(a) was a significant risk factor in all four studies. In the recent prospective case‐control study, Lp(a) and cholesterol were found to act synergistically and predict primary acute myocardial infarction in Swedish males. A cholesterol level above 6.5 mmol/1 increased the risk of acute myocardial infarction if the Lp(a) level was above 200 mg/1. The plasma apo A‐I level was a protective factor. In the other recent case‐control study, an Lp(a) level above 500 mg/1 was a highly significant risk factor in Black and White US women with myocardial infarction or advanced coronary artery disease in addition to low density lipoprotein cholesterol levels above 130 mg/dl. A high apo A‐I level was a protective factor. In these studies no other factors tested reached significance in multivariate logistic regression analysis. A hypothetical association between high Lp(a) levels and intracellular infection withChlamydia pneumoniaeis discussed. The results suggest that the Lp(a) level is useful in identifying high‐risk individuals. Lowering low density lipoprotein cholesterol below 100 mg/dl (7lt;2.6 mmol/1) seems to be most important in both males and females with high‐risk Lp(a) levels.
Genotype ‐phenotype correlation in myotonic dystrophy
Authors: Gharehbaghi‐Schneli Elisabeth B. , Finsterei Josef , Korschineck Irina , Mamoli Bruno , Binder Bernd R.
Published: July 2010

Myotonic dystrophy (DM) is caused by a mutation in the length of a trinucleotide (CTG) repeat in the 3' untranslated region of the my‐otonin protein kinase gene located on chromosome 19q13.3. The normal gene has between 5 and 36 CTG trinucleotide repeats, whereas minimally affected individuals have 50 copies and severely affected DM‐patients have several thousands of such repeats. Since no information on a genotype‐phenotype correlation in Austrian DM‐patients is available, we examined a small group of these patients for the unstable trinucleotide repeat. Molecular analysis was used to clarify equivocal clinical diagnoses and confirm clinical findings. We studied eight DM‐families, a total of 57 individuals, of whom 18 were diagnosed with a trinucleotide repeat expansion. Twenty‐six unrelated individuals served as a control. Clinical assessment was based on the muscular disability rating scale (MDRS) and a sum of symptoms score (SSS). There was a significant correlation between the clinical scores (MDRS: Spearman r = 0.51: p = 0.029; SSS: Spearman r = 0.538; p = 0.0259) used and the size of the amplification of the trinucleotide repeat. The largest expansion found in our group of patients was 6 kb. Furthermore, we observed both expansion and contraction of the enlarged fragment during transmission from one generation to the next.
A clinical, cytogenetic and molecular study of ten probands with supernumerary inv dup (15) marker chromosomes
Authors: Webb T. , Hardy CA , King M. , Watkiss E. , Mitchell C. , Cole T.
Published: July 2010

Ten probands with moderate to severe developmental delay were found to have a supernumerary inv dup (15) chromosome. These patients and their families were studied by both cytogenetic and molecular methods. Cytogenetic polymorphisms associated with the 15p short arm suggested a maternal derivation for the marker chromosome in all informative cases. One marker was directly maternally inherited. Molecular analysis employing Southern blotting and polymerase chain reaction (PCR) of microsatellite repeats demonstrated the presence of extra alle‐les in the 15q11q13 region. All ten of the probands demonstrated an extra band at one or more locus without recourse to densitometry. All of the inv dup (15) markers were comparable in size to a G group chromosome but there were differences in the positions of the breakpoints in 15q. There was an inconsistent relationship between marker size, gene dosage and severity of phenotype.
Association between asthma and an intragenic variant of CC16 on chromosome 11q13
Authors: Mao X‐Q , Shirakawa T. , Kawai M. , Enomoto T. , Sasaki S. , Dake Y. , Kitano H. , Hagihara A. , Hopkin JM , Morimoto K.
Published: July 2010

The β subunit of high affinity immunoglobulin E (IgE) receptor (FceRIβ) and the Clara cell derived inflammatory molecule, CC16 have been cited as candidate genes for atopic asthma on chromosome 11q13. A genetic association study was performed with an intragenic microsatellite repeat of CC16 gene on chromosome 11q12–13 in relation to atopic and non‐atopic asthma. Whereas variants of FceRIβ at chromosome 11q13 show association with atopy and asthma, no significant association was found between asthma and CC16 genotypes irrespective of atopic status. These data support the candidacy of FcsRIβ rather than CC16 for the atopic asthma locus on chromosome 11q.
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.
A new case of Ambras syndrome associated with a paracentric inversion (8) (q12; q22)
Authors: Balducci R. , Toscano V. , Tedeschi B. , Mangiantini A. , Toscano R. , Galasso C. , Cianfarani S. , Boscherini B.
Published: July 2010

Ambras syndrome (AS) is a special form of congenital universal hypertrichosis described for the first time by Baumeister et al. (1). This form differs from other forms of congenital hypertrichosis in the pattern of hair distribution and its associated anomalies. The molecular‐genetic cause of AS is unknown; the association of AS with a pericentric inversion (8) (p11.2; q22) described in the case of Baumeister so far has been unique in the literature. This report is the tenth with clinical signs of AS so far described in the literature and the second with an inversion in chromosome 8 and the first with evaluation of peripheral androgens. The new‐born girl presented with abundant and dark hair on the face and ears, on the shoulders and on the arms; the other parts of the body were covered with fine, lightly pigmented hair. The face showed many dysmorphic features. Chromosome analysis showed a paracentric inversion of one chromosome 8. The breakpoints were localised at q12 and q22. The parental karyotypes were normal. Laboratory investigation showed normal plasma levels of testosterone, androstenedione (A), 17‐hydroxyprogesterone, dehydroepiandrosterone‐sulphate (DHA‐S), free testosterone (FT), dihydrotestosterone (DHT) and 3α‐androstanediol‐glucuronide (3AG). Here we report a chromosomal inversion similar to that found previously not associated with alterations in androgen plasma levels.
Presenilin 1 Met146Leu variant due to an A&T transversion in an early‐onset familial Alzheimer's disease pedigree from Argentina
Authors: Morelli Laura , Prat María I. , Levy Efrat , Mangone Carlos A. , Castaño Eduardo M.
Published: July 2010

Most of the cases of early‐onset familial Alzheimer's disease (FAD) are related to missense mutations in the presenilin 1 (PS‐1) gene on chromosome 14. Although PS‐1 mutations are distributed throughout the entire open reading frame, most mutations are found in transmembrane region II and hydrophilic loop VI encoded by exons 5 and 8, respectively. These two groups of substitutions are associated with an age of onset of 40–43 years for exon 5 and 45–55 years for exon 8, respectively. We have previously described a South American pedigree from Argentina with early‐onset FAD (mean age of onset 38.9 ± 3.9 years) with no mutations in exons 16 and 17 of the β‐protein precursor gene (βPP770 transcript). Here we report the identification of an A±T transversion at the first position of codon 146 of PS‐1 in these patients. This missense mutation results in a Met ± Leu substitution, as reported for the Italian pedigrees Tor 1.1 and FAD4. The significant differences in ages of onset and death among members of generations II—III and IV suggest that other genetic and/or environmental factors may influence disease phenotype in this pedigree.
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.
Rapid determination of trisomy 18 parental origin using fluorescent PCR and small tandem repeat markers: case reports
Authors: Findlay Ian , Tóth Tamás , Matthews Paul , Marton Tamás , Quirke Philip , Papp Zoltán
Published: July 2010

Trisomy 18 is the second most common genetic defect after trisomy 21, almost 90% of which are due to additional chromosome from the mother. The parental origin of the additional chromosome can, if required, be determined by two methods: karyotyping, which takes several weeks; or, more recently, by polymerase chain reaction (PCR) which is often problematic. Fluorescent PCR of small tandem repeats (STRs) can determine the parental origin in the majority of cases within 5 h. Although the incidence of paternal origin is known for both trisomy 21 and trisomy 18, this technique can rapidly determine the parental origin in cases where there is insufficient samples to perform conventional tests. Determining parental origin by these methods may also have clinical significance in the diagnosis of chromosomal translocations or in the diagnosis of genetic disease using linkage analysis.
Vascular anastomoses leading to amelia and cutis aplasia in a dizygotic twin pregnancy
Authors: Phelan Mary C , Geer Joseph S , Blackburn Will R
Published: July 2010

Dichorionic placentation is observed in both monozygotic (MZ) and dizygotic (DZ) twinning, while monochorionic placentation is unique to MZ twinning. Examinations of monochorionic twin placentas frequently reveal the presence of vascular anastomoses between the two fetal circulations; such anastomoses rarely occur in dichorionic placentas. Consequently, abnormalities resulting from placental vascular communications are almost exclusively observed in MZ twin pairs with monochorionic placentas. We report opposite‐sex DZ twins in which vascular anastomoses occurred within a fused dichorionic placenta and were associated with vascular disruptions in one twin. The liveborn male twin had amelia, cutis aplasia, and XX/XY blood chimerism; the female twin died in utero.
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.
No relation between apolipoprotein E alleles and obstructive sleep apnea
Authors: Saarelainen Seppo , Lehtimäki Terho , Kallonen Eija , Laasonen Kirsi , Poussa Tuija , Nieminen Markku M
Published: July 2010

Apolipoprotein E (ApoE) is a genetic risk factor influencing the development of cardiovascular diseases and Alzheimer's disease. Patients with obstructive sleep apnea (OSA) suffer an excess mortality and morbidity from cardiovascular diseases. The frequencies of ApoE alleles were determined in 291 patients with OSA and 728 controls. The distribution of ApoE alleles and genotypes showed no difference between OSA and controls.
Developmental Biology: Frontiers for Clinical Genetics: Overgrowth syndromes and genomie imprinting: from mouse to man
Authors: Li M. , Squire JA , Weksberg R.
Published: July 2010

Beckwith‐Wiedemann syndrome (BWS), a human overgrowth syndrome with a complex genetic basis, is caused by alterations to chromosome 11p15, a region subject to genomie imprinting. These alterations include translocations, duplications, single gene mutations of p57KIP2, and increased expression of insulin‐like growth factor 2 (IGF2). A phenotypically related X‐linked overgrowth syndrome, Simpson‐Golabi‐Behmel syndrome (SGBS), is caused by alterations in glypican‐3 (GPC3), a molecule that may interact with the gene products identified to be important in generating the BWS phenotype, that is, IGF2 and p57KIP2. The crucial defect in these overgrowth syndromes is likely to be an imbalance in contributions of growth‐promoting genes versus growth‐inhibitory genes in critical tissues at specific developmental stages. Murine models have been used to study the effects of targeted deletions of the genes p57KIP2 and GPC3, as well as overexpression of IGF2. At this time, there are still many issues which remain to be explored before we can fully understand the molecular basis of BWS and SGBS.
DNA diagnosis of FRAXA and FRAXE in Chinese children with neurodevelopmental disorders and fragile X syndrome
Authors: Chan SY , Wong V.
Published: July 2010

Fragile X (FraX) syndrome is the most common cause of inherited mental retardation. To see whether FRAXA or FRAXE can account for the etiology of some unexplained neurodevelopmental disorders in children, we screened for trinucleotide repeat expansion in a consecutive cohort of 73 Chinese children and their mothers seen in 1995 (group 1) referred for developmental assessment due to developmental delay, language delay, attention deficit hyperactivity disorder, autistic spectrum disorder, mental retardation and/or learning disability. We also screened DNA samples of all five previously diagnosed cytogenetically‐positive FraX boys, their mothers and sisters (group 2). A control group of unrelated teenagers and adults were recruited from the community (group 3). In group 1, 3 families (2 mothers and a mother and her son) were found to carry a small premutation allele at FRAXA (premutation frequency = 2%, 3/153 independent X chromosomes), but none had any expansion at FRAXE. In group 2, all 5 FraX boys had full mutation at FRAXA and normal repeat length at FRAXE. In group 3, 1 male has a premutation allele out of 18 males and 59 females tested (premutation frequency of control = 0.7%, 1 out of 136 X chromosomes). For FRAXE screening in group 3, 2 females were carriers (1.5%, 2 out of 136 X chromosomes). Thus, FRAXA and FRAXE cannot account for the etiology of neurodevelopmental disorders in our cohort of Chinese children, and the prevalence of FRAXE mutation in normal Chinese population appears to be higher than reported in the Caucasians.
The intermediate alleles of the fragile X CGG repeat in patients with mental retardation
Authors: Mornet Etienne , Chateau Corinne , Simon‐Bouy Brigitte , Serre Jean‐Louis
Published: July 2010

We have analysed the size of the non‐expanded FRAXA CGG repeat in 385 male patients affected by mental retardation and in 182 unrelated normal chromosomes as control. The results show that intermediate alleles with more than 40 repeats were not significantly more frequent in patients than in controls. These data do not corroborate previous findings supporting the idea that intermediate alleles may have a deleterious effect on mental retardation.
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.
Detection of mtDNA deletion in Pearson syndrome by two independent PCR assays from Guthrie card
Authors: Tóth Tamás , Bókay János , Szönyi László , Nagy Bálint , Papp Zoltán
Published: July 2010

Pearson syndrome is a multisystem juvenile condition associated with deletions in the mitochondrial genome. The most common 4977 bp deletion of mitochondrial DNA (mtDNA) can mainly be detected in the patients' peripheral blood. Here we report a child with a clinically unclarified diagnosis where molecular genetic results proved Pearson syndrome from stored dried blood sample 6 months after the patient's death. PCR amplification around the breakpoint of the most common mtDNA deletion could detect the presence of mutated mtDNA. Another polymerase chain reaction (PCR) assay indicated the low level of wild type mtDNA in patients' blood. We believe that this case shows the importance of storing Guthrie card and the availability of detection of Pearson syndrome from dried blood sample.
Polymorphisms at the angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) loci and normal blood pressure
Authors: Berge KE , Berg K.
Published: July 2010

The M235T polymorphism at the angiotensinogen (AGT) locus and the A1166C polymorphism at the angiotensin II type 1 receptor (AT1R) locus have been reported to be associated with hypertension in several populations. We examined these polymorphisms in three samples of healthy Norwegians with respect to normal blood pressure (BP) levels. None of the genotypes defined by the polymorphisms or their combinations were associated with systolic (S) BP (SBP) or diastolic (D) BP (DBP) level. However, there was a trend in all three series that individuals carrying the C allele of the A1166C polymorphism at the AT1R locus (homozygotes as well as heterozygotes) had higher SBP, than AA homozygous individuals. The observation did not reach statistical significance in any of the series. When examining these two polymorphisms with respect to possible variability gene effects on BP in two series of monozygote (MZ) twin pairs, no such effect was detected. We could not detect any interaction between the loci studied with respect to BP level or variability. Thus, neither the AGT locus nor AT1R locus, separately analysed or together, seem to have variability gene effects or definite level gene effects on normal BP.
Wilms' tumor and gonadal dysgenesis in a child with the 2q37.1 deletion syndrome
Authors: Viot‐Szoboszlai G. , Amiel J. , Doz F. , Prieur M. , Couturier J. , Zucker JN , Henry I. , Munnich A. , Vekemans M. , Lyonnet S.
Published: July 2010

Here we report Wilms' tumor, gonadal dysgenesis and a bifid uterus in an 18‐month‐old female with a terminal deletion of the long arm of chromosome 2 [46, XX, del(2)(q37.1)]. Since Wilms' tumor has been previously reported in the 2q37 deletion syndrome, the present observation raises the question of whether a tumor susceptibility gene maps to chromosome 2q37 and suggests giving consideration to the possible occurrence of Wilms' tumor in the course of disease.
A novel mutation of the β‐glucocererebrosidase gene associated with neurologic manifestations in three sibs
Authors: Parenti Giancarlo , Filocamo Mirella , Titomanlio Luigi , Rizzolo M Grazia , Silvestro Eufrasia , Perretti Anna , Gatti Rosanna , Andria Generoso
Published: July 2010

We report on a sibship in which three members were affected by Gaucher disease. Molecular analysis of the patients showed homozygosity for a novel mutation (C5390G) of the β‐glucocerebrosidase gene, resulting in the substitution of the arginine 353 with a glycine. Western blot analysis showed a reduced amount of β‐glucocerebrosidase‐related polypeptides in fibroblasts. The phenotype resulting from this mutation is characterized by visceral and skeletal manifestations. In addition, the presence of seizures and electrophysiological abnormalities only in the 3 patients and in none of the other unaffected sibs suggests that the mutation is responsible for neurologic involvement.
Complex chromosomal rearrangements associated with congenital erythrophagocytotic histiocytosis
Authors: Edelhoff Susanne , Grond‐Ginsbach Caspar , von Eggeling Ferdinand , Körholz Dieter , Göbel Ulrich , Senger Gabriele
Published: July 2010

We describe a patient with a congenital malignant blood disorder and a constitutional de novo chromosomal rearrangement that includes four breakpoints. By conventional cytogenetic analysis an obviously reciprocal balanced translocation with the breakpoints 1p36 and 5q11.2 was diagnosed. Due to a suspicious dark band in the breakpoint area of 1p a more detailed analysis of the breakpoints was performed using microdissection and reverse chromosome painting. This revealed a small inversion at 1p36 that must have occurred prior to the reciprocal translocation. The three breakpoints in chromosome 1 (1p36.11, 1p36.21 and 1p36.31) are within or close by regions known to contain tumor suppressor genes. The chromosomal rearrangement might have resulted either in a submicroscopic deletion, in loss of heterozygosity of one or more imprinted genes, or in gene position effects as possible explanations for the clinical course of our patient.
Apparent normalisation of fetal renal size in autosomal dominant polycystic kidney disease (PKD1)
Authors: Jeffery Steve , Saggar‐Malik Anand K , Economides Demetrios L , Blackmore Sally E , MacDermot Kay D
Published: July 2010

We present a family with adult onset autosomal dominant polycystic kidney disease (ADPKD) in two generations, linked to the PKD1 locus and with paternal transmission to the fetus. The fetus carried the PKD1 haplotype and was, therefore a gene carrier. Progressive hyperechogenic renal enlargement, but no cysts, was documented by serial fetal ultrasounds at 21, 23 and 34 weeks of gestation. Surprisingly, the newborn renal scan showed normal sized kidneys with apparently normal corticomedullary differentiation. However, at 11 months of age, the evolution of cysts in one kidney, and then in the other kidney at 20 months, was documented by ultrasound in the absence of clinical symptoms or signs. The observed normalisation of fetal renal ultrasound appearances at birth has not previously been described in fetuses presenting with PKD1.
Developmental Biology: Frontiers for Clinical Genetics: Limb development: molecular dysmorphology is at hand!
Authors: Innis Jeffrey W , Mortlock Douglas P
Published: July 2010

We present a review of limb development integrating current molecular information and selected genetic disorders to illustrate the advances made in this field over the last few years. With this knowledge, clinical geneticists can now begin to consider molecular mechanisms and pathways when investigating patients with limb malformation syndromes.
Clinical, biochemical and molecular findings in a two‐generation Morquio A family
Authors: Tylki‐Szymańska Anna , Czartoryska Barbara , Bunge Susanna , van Diggelen Otto P , Kleijer Wim J , Poor‐trims Ben JHM , Huijmans Jan GM , Górska Danuta
Published: July 2010

Mucopolysaccharidosis type IVA (Morquio A) is caused by a deficiency of N‐acetylgalactosamine‐6‐sulfatase (GALNS), an enzyme capable of cleaving the sulfate group from both N‐acetylgalactosamine‐6‐sulfate and galactose‐6‐sulfate. We describe here a two‐generation Morquio A family with two distinct clinical phenotypes. The two probands from the second generation showed intermediate signs of the disease whereas their affected mother, aunt and two uncles had only very mild symptoms. Galactose‐6‐sulfatase (GALS) activity in leukocytes and fibroblasts of the affected family members was clearly deficient. Molecular genetic analysis of the GALNS gene revealed that two different point mutations segregate in the family, which correlated well with the clinical phenotype. The probands with intermediate symptoms were compound heterozygotes for the mutations R259Q and R94G, the latter one being inherited from the unaffected father. The mother and her affected siblings with the unusually mild phenotype were proven to be homozygous for the novel missense point mutation R259Q.
Mild cystic fibrosis mutations in Southern Sweden with special reference to S549I and T338I
Authors: Schaedel C. , Andersson A‐M , Kristoffersson A‐C , Kornfält R. , Lannefors L. , Holmberg L.
Published: July 2010

In this study of cystic fibrosis (CF) gene mutations in Southern Sweden we found missense mutations in 12 out of 110 patients. These patients, as a group, differed from ΔF508 homozygotes by a higher frequency of pancreatic sufficiency and an older age at diagnosis as has been indicated in previous studies. In addition, lung function (vital capacity (VC) and forced expiratory volume in 1 s (FEV1)) tended to be better although the difference did not reach statistical significance (p = 0.13 for FEV1). For two mutations, S549I and T338I, our results differed from earlier reports. In our experience, S549I confers a milder phenotype and T338I a more severe one than previously reported. We conclude that each mutation should be treated separately when trying to correlate genotype with phenotype.
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.
Noonan syndrome associated with central giant cell granuloma
Authors: Uçar Birsen , Ökten Aysenur , Mocan Hilal , Erçin Cengiz
Published: July 2010

We report a case of Noonan syndrome associated with central giant cell granuloma. The patient was a 101/2‐year‐old boy with the chief complaint of proptosis of the right eye. He also had various malformations such as short stature, webbed neck, pectus excavatum, cubitus valgus, pulmonary valve stenosis and patent foramen ovale, a characteristic face appearance and cryptorchidism and so on. Chromosome analysis showed a 46, XY karyotype. A computed tomographic scan and magnetic resonance imaging showed a mass originated from the lateral wall of the right maxillary sinus. The patient underwent Caldwell‐Luc operation. Histological examination of the mass showed the characteristics of central giant cell granuloma. This case report describes a patient with the features of the recently described Noonan‐like/multiple giant cell lesion syndrome.