bluuebunny/crossref_metadata_2025 huggingface dataset:
Fine mapping of X‐linked clasped thumb and mental retardation (MASA syndrome) in Xq28
Authors: Legius E. , Kaepernick L. , Higgins J. V. , Glover T. W.
Published: July 2010

The MASA syndrome is an X‐linked disorder with mental retardation, spastic paraparesis, and adducted thumbs as the most characteristic features. We performed linkage analysis, using Xq28 markers, on a large MASA syndrome family. The maximum lodscore was 6.37 at 0 recombination for DXS52 and 5.99 at 0 recombination for DXS305. Crossovers were demonstrated between the disorder and DXS455. Clinical and linkage data from this family further support the hypothesis that the MASA syndrome and X‐linked hydrocephalus are allelic disorders.
Fragile X syndrome with extra microchromosome
Authors: López‐Pajares I. , Delicado A. , Pascual‐Castroviejo I. , López‐Martin V. , Moreno F. , Garcia‐Marcos J. A.
Published: July 2010

A mentally retarded male with Martin‐Bell syndrome, who has an extra microchromosome and is fra X negative in cytogenetic study is reported. Because of its small size, the origin of the microchromosome could not be determined. Two other affected males in this family (a cousin and a nephew of the proband) were fragile X positive, 24% and 26%, respectively. Cytogenetic studies and DNA analysis with the probe St B 12.3 were performed on several members of the family. The proband and the two other affected males showed a similar full mutation on the molecular study. This study emphasizes the importance of molecular analysis in the diagnosis of fragile X syndrome, particularly when cytogenetic studies demonstrate fra X negative in individuals in families likely to have X‐linked mental retardation.
Hereditary pubertal genu valgum in Iran
Authors: Ghorbani K. , Carapetian J.
Published: July 2010

Two male offspring of a healthy father in Galaz, a remote village in Northwest Iran, were noted to show severe asymmetric genu valgum, with 57 and 82 degrees angulation and dysplasia of the lateral femoral condyle, together with adaptive biomechanical changes of the ankle alignment. Three of the five male offspring of a second marriage who have reached puberty also show variable degrees of genu valgum, increasing with growth. The intermalleolar distance in the affected sons aged 16, 15, and 12 measured 21, 16, and 14 cm, respectively, before epiphysodesis. None of the six female offspring from either marriage, and neither of the two sons under the age of 11 from the second marriage show any skeletal deformity. All members of the family are otherwise mentally and physically normal. It is possible that this genu valgum may be due to a new autosomal dominant mutation which probably occurred in the gonads of the unaffected father. The condition shows an onset age of 11 and appears to have a sex‐limited expression.
The primary hereditary form of distal renal tubular acidosis: clinical and genetic studies in 60‐member kindred
Authors: Chaabani Hassen , Hadj‐Khlil Amel , Ben‐Dhia Naceur , Braham Hammadi
Published: July 2010

A distal (type 1) renal tubular acidosis (RTA‐1) has been studied in 60 of 69 living members of a large family “HK” and two unrelated small families. The “HK” family, including 28 RTA‐1 subjects, presents the first large family with only primary RTA‐1 reported to date. The genetic situation in this family confirms the autosomal dominant transmission of the hereditary primary RTA‐1 suggested previously on the basis of a few small families. Our data show that, in contrast to the secondary hereditary form, RTA‐1 in its primary hereditary form is always complete and often tolerated (asymptomatic). It occurs in non‐hypercalciuric families with no clinical variants observed in family members without RTA‐1. In our series some clinical abnormalities commonly associated with RTA‐1, such as nephrocalcinosis and growth retardation, appeared only in three cases among offspring when both parents were affected. The appearance of such abnormalities, taken as consequences of chronic acidosis in RTA‐1, could be favored by the genetic background and/or the homozygosity for the RTA‐1 gene. Linkage studies between RTA‐1 and 10 genetic markers have been carried out. Results show that only ABO, MNS, GM and RH loci are informative for linkage analysis and none of these loci can be suggested as linked to RTA‐1 locus.
Onychotrichodysplasia and chronic neutropenia without mental retardation (ONS): a second case report
Authors: Dallapiccola B. , Mingarelli R. , Obregon G.
Published: July 2010

Onychotrichodysplasia, chronic neutropenia and mental retardation syndrome (ONMRS) is a rare autosomal recessive mutation, mostly reported in patients of Mexican ancestry. We describe a second patient with onychotrichodysplasia and chronic neutropenia without mental retardation (ONS). It is unclear if ONS found in the two European patients with normal mental development is due to genetic heterogeneity or variable expressivity of the same syndrome.
Effects of consanguinity on anthropometric measurements of newborn infants
Authors: Başaran N. , Artan S. , Yaziciogllu S. , Şayli B. S.
Published: July 2010

The effects of parental consanguinity on gestational age and birth measurements were evaluated on 2880 newborn infants. Consanguineous marriages were considered in three subgroups: first‐cousin, first‐cousin‐once‐removed and distant‐cousin marriages, versus non‐consanguineous marriages. Anthropometric parameters were weight, length, leg length, head, chest and mid‐arm values obtained within 24 h of birth. No significant differences were found concerning gestational age. Although anthropometric values were slightly less, especially in children from first‐cousin couples, the differences were insignificant for all groups. It was concluded that blood‐relationship alone does not affect such multifactorial traits.
De novo isochromosome 18p in two patients: cytogenetic diagnosis and confirmation by chromosome painting
Authors: Back Elke , Toder Roland , Voiculescu Ion , Wildberg Anke , Schempp Werner
Published: July 2010

This report concerns two patients with clinical features typical for tetrasomy 18p syndrome. Chromosomal analysis revealed a male karotype in both cases, with an additional small metacentric marker chromosome, putatively an i(18p). Fluorescent in situ hybridization with a chromosome 18‐specific paint confirmed that the marker chromosome consisted of chromosome 18 material in both cases.
A new case of “complete” trisomy 5p with isochromosome 5p associated with a de novo translocation t(5;8)(q11;p23)
Authors: Fujita M. , Flori E. , Lemaire F. , Casanova R. , Astruc D.
Published: July 2010

A boy with a de novo translocation t(5;8)(q11;p23) and an isochromosome 5p is described. The main clinical features found in the complete trisomies 5p are reviewed and the mechanisms of the chromosomal rearrangements involving centromeric and telomeric regions are discussed.
Linkage analysis of 62 X‐chromosomal loci excludes the X chromosome in an Icelandic family showing apparent X‐linked recessive inheritance of neural tube defects
Authors: Newton R. , Stanier P. , Loughna S. , Henderson D. J. , Forbes S. A. , Farrall M. , Jensson O. , Moore G. E.
Published: July 2010

We report here the findings of a linkage analysis, involving numerous markers from the human X chromosome, in an attempt to localise a putative gene causing apparent X‐linked spina bifida and anencephaly (SBA) in a large Icelandic pedigree. Two‐point linkage analysis was performed using markers from 62 informative loci in this family. Although small positive lod scores were found at a number of these loci, none reached the significance level for linkage. Haplotypes were extensively analysed and found to exclude linkage to the X chromosome.
Increased frequency of apolipoprotein B signal peptide sp24/24 in patients with coronary artery disease. General allele survey in the population of Taiwan and comparison with Caucasians
Authors: Wu J. H. , Wen M. S. , Lo S. K. , Chern M. S.
Published: July 2010

Apolipoprotein B (apoB) signal peptide (sp) polymorphism was characterized by polymerase chain reaction in blood samples of 58 coronary artery disease (CAD) patients and 319 control individuals of Chinese Han ethnic origin in Taiwan. In the CAD group, 77% of the observed alleles were sp27 (sp with 27 amino acids), and the remaining 23%sp24 (sp with 24 amino acids). The frequency distributions of the apoB sp allele in the control group were 0.81 for sp27 and 0.19 for sp24. The genotype distributions were 0.64 sp27/27, 0.26 sp27/24 and 0.10 sp24/24 in the CAD group; 0.64 sp27/27. 0.33 sp27/24 and 0.03 sp24/24 in the control group. The frequency of sp24/24 was significantly higher (p= 0.012) in the CAD group than in the control group. Several studies have shown that the frequency of sp24/24 is higher in hyperlipidemic than in normolipidemic groups. This marker is probably in linkage disequlibrium with some other atherogenic genes. Our study shows that the differences in both apoB signal peptide alleles and sp27/27 and sp27/24 genotype distributions are statistically significant between the Taiwanese and Caucasians.
Allele frequencies of Mp6D‐9 and GATT markers in 32 Turkish cystic fibrosis families
Authors: Özgüç M. , Yilmaz E. , Erdem H. , Coşkun T. , Özçelik U. , Togan I. , Göçmen A. , Ayter S. , Özalp I.
Published: July 2010

The allele frequency of GATT and Mp6D‐9 markers was investigated in 32 cystic fibrosis (CF) families. The GATT6 allele was found to be significantly associated with the ΔF508 mutation. The Mp6D‐9 allele 2/GATT6 haplotype was the major haplotype of the mutant alleles. Further analysis of CF alleles for population‐specific mutations is underway so that a more direct approach can be taken, especially for families seeking prenatal diagnosis.
The KBG syndrome: follow‐up data on three affected brothers
Authors: Soekarman Dominique , Volcke Philippe , Fryns Jean‐Pierre
Published: July 2010

In this report we present follow‐up data on a family in which several members were found to have short stature, craniofacial anomalies and dento‐skeletal abnormalities (KBG‐syndrome). As adults, the three affected brothers of the original report are moderately to severely mentally retarded. Their phenotype with a distinct craniofacial appearance did not change much from that seen during childhood and adolescence. Adult height is far below the third centile, with arm spans exceeding stature by at least 9 cm.
HLA‐A, B and DR antigens in patients with gonadal dysgenesis
Authors: Filipović Boris , Dumić Miro , Tomašković Marija , Crnojević Ružana , Ille Jasenka , Vuković Jurica
Published: July 2010

HLA (human leukocyte antigens) antigens A, B, and DR were determined in a series of 50 patients with gonadal dysgenesis (GD), separated into different groups according to karyotype. There were no significant differences in frequency of HLA antigen types between GD patients and the population control. When frequencies of the HLA antigens in the various GD patient groups by karyotype were compared, only one significant difference was found: HLA‐A3 was more common among GD patients with isochromosome X than among GD patients with karyotype 45, X (p<0.001, corr. p<0.008). Although GD patients have a higher expectancy for development of autoimmune disorders, and in our 50 patients thyroglobulin and/or microsomal antibodies were detected in 20 (i.e., 40%), we failed to find any increased frequency of specific HLA antigen types known to be associated with juvenile autoimmune thyroiditis.
Marfan and cri du chat syndromes in an 18‐month‐old child: evidence of phenotype interaction
Authors: McClellan Michael W. , Golden Wendy L. , Wilson William G.
Published: July 2010

We report on an 18‐month‐old girl who has both the cri du chat and Marfan syndromes. She was born at term to a 29‐year‐old woman with the clinical diagnosis of Marfan syndrome. An evaluation for developmental delay at 2 months of age showed a karyotype of 46,XX,del(5)(15.1), consistent with cri du chat syndrome. At age 18 months she was tall (90 cm, >95th centile), with an decreased upper segment:lower segment ratio (1.0), and microcephalic (OFC 42.5 cm, <5th centile). Facial features were typical of cri du chat syndrome. The palm, middle finger and foot lengths were at or above the 95th centile for age. She was hypotonic, and her developmental level was approximately 8–10 months. Echocardiography showed redundant mitral valve tissue, mild mitral insufficiency, dilated aortic sinuses, and a small muscular VSD. We would have anticipated that a patient with an autosomal deletion who also had Marfan syndrome would have had growth failure. However, in this patient the skeletal features of Marfan syndrome (increased body length, decreased upper segment:lower segment ratio, and increased palm, finger, and foot length) predominate.
A stigmatizing effect of the carrier status for cystic fibrosis?
Authors: Evers‐Kiebooms Gerry , Denayer Lieve , Welkenhuysen Myriam , Cassiman Jean‐Jacques , Van den Berghe Herman
Published: July 2010

The emotional impact of carrier detection for CF was assessed in a group of adults tested before 1992. Of the 200 adults who received a mailed questionnaire, 70% participated. One third were CF gene carriers. The Health Orientation Scale (HOS) was used to evaluate perceived feelings about three situations: (a) How would you describe your feelings about yourself when you consider your test result? (b) How do you think most people feel when they are told that they carry the CF gene? (c) How do you think most people feel when they are told that they do not carry the CF gene? Comparing the profiles of CF carriers and non‐carriers, we found that carriers had significantly less positive feelings about themselves than non‐carriers. Carriers as well as non‐carriers attribute significantly more negative feelings to most carriers of the CF gene than to most non‐carriers. Moreover, carriers of the Cf gene attribute more negative feelings to other CF carriers than to themselves. Analysis of variance revealed a significant effect of carrier status on self‐description, as well as a significant effect of carrier status and degree of kinship with a CF patient on feelings attributed to most carriers. Although these results suggest some danger of stigmatization of CF carriers, the cognitive bias of ‘illusory superiority’ seems to counterbalance some of its effects.
Prenatal sex determination by in situ hybridization on fetal nucleated cells in maternal whole venous blood
Authors: Björkqvist Anna‐Maria , Slunga‐Tallberg Anna , Wessman Maija , Ylinen Kari , Knuutila Sakari
Published: July 2010

Our aim was to evaluate whether the sex of a fetus could be determined in maternal whole venous blood by in situ hybridization without enrichment of fetal cells. This procedure is virtually without risks to the fetus or the mother. Blood samples were obtained from 59 women at different stages of pregnancy. Twenty preparations were discarded because they were technically unfit for in situ hybridization. Of the remaining 39 pregnant women. 18 had a male fetus, one had male twins, and 20 had a female fetus. Y‐positive cells were detected in 12 of the 19 pregnancies with male fetuses and in two of the 20 pregnancies with a female fetus. The frequencies of cells with Y‐signals ranged from 1 in 100 000 to 1 in 639. Our results show that fetal cells in maternal blood cannot be reliably used for prenatal diagnosis without prior enrichment of fetal cells.
Molecular characterisation of an Italian G6PD variant responsible for chronic non‐spherocytic haemolytic anaemia
Authors: di Montemuros Franco Martinez , Cappellini Maria Domenica , Dotti Chiara , Tavazzi Dario , De Bellis Gianluca , Debernardi Silvana , Fiorelli Gemino
Published: July 2010

An Italian deficient G6PD variant associated with chronic non‐spherocytic haemolytic anaemia (CNSHA) was biochemically characterised and studied at molecular level. Single‐strand conformation polymorphism (SSCP) analysis led to the identification of an abnormal migration pattern of an amplified fragment encompassing exons 10 and 11 of the G6PD gene. Sequence analysis of both strands using an automated fluorescent DNA sequencer revealed a GA transition at nt. position 1246 in exon 10. A CT substitution at nt. 1311 in exon 11 was also found, which has already been described as a silent mutation common in Caucasians. The 1246 GA mutation has been described only in a Japanese subject with CNSHA (G6PD Tokyo) not associated with the 1311T polymorphism, suggesting that this mutation may have arisen independently in Europe and Asia.
Identification of a non‐fluorescent isodicentric Y chromosome by molecular cytogenetic techniques
Authors: Macera Michael J. , Sherman Jack , Shah Harshad O. , Blumberg Denise L. , Buttice Linda S. , Lin Jen H. , Verma Ram S.
Published: July 2010

A 12 1/2‐month‐old girl was referred because of short stature, short neck, large internipple distance and simian crease on her right hand. By routine cytogenetic techniques the presence of an unidentifiable marker chromosome and loss of one X chromosome was noted (i.e. 45, X/46, X, mar/47, X, mar, +mar). By fluorescence in situ hybridization (FISH) technique, the marker chromosome was identified as an isodicentric non‐fluorescent Y chromosome ((45, X/46, X, idic (Ynf)/47, X, idic (Ynf), +idic (Ynf)). Although the clinical significance of this finding cannot be assessed at present, possible development of gonadoblastoma in such cases is a major concern and warrants follow‐up evaluations.
Confounding results of Lp(a) lipoprotein measurements with some test kits
Authors: Berg Kåre
Published: July 2010

A small number of recent studies have reportedly failed to detect the well‐established association between a high Lp(a) lipoprotein level and coronary heart disease (CHD). This has made some workers question the importance of a high Lp(a) lipoprotein level as a CHD risk factor. However, serious problems with some of the commercially available test kits, inadequate test techniques or failure to consider the lability of the Lp(a) lipoprotein particle are more plausible explanations of the confounding results. The problems with some of the commercially available test kits include lack of standardization and validation; risk of cross‐reactivity with plasminogen or other serum proteins; failure to consider potential problems when measuring samples with varying length of the Lp(a) polypeptide chain (i.e. failure to cope with the isoform variation); non‐divulgence of contents of test reagents; and pretreatments of samples that drastically change the Lp(a) lipoprotein particles from their native state. Any test system should be validated at the scientific level before it is assumed to provide correct measurements of Lp(a) lipoprotein level in serum. New test kits should be safely anchored in validation in one of the research laboratories active in the area, before they are put on the market. As new batches are produced, the quality of every new batch of test kits should be monitored on a long‐term basis in collaboration with a research laboratory.
From Ag phenotyping to molecular genetics: apolipoprotein B, serum lipid levels and coronary artery disease in Finland
Authors: Tikkanen Matti J. , Heliö Tiina
Published: July 2010

The Ag polymorphisms of low density lipoproteins (LDL) were described in the 1960's (Allison & Blumberg 1961, Bütler 1967). The first report suggesting that they may be associated with serum lipid levels did not appear until 1976 (Berg et al. 1976). Out of the 10 populations studied, the Finnish population showed the most marked association between Ag(x —) phenotype and elevated serum cholesterol and triglyceride levels. After this, little progress was made for several years, possibly because Ag antibodies were available in very few laboratories. The introduction of monoclonal antibodies directed against apo B in the 1980's provided a novel means to detect immunophenotypes of LDL (for review, see Tikkanen 1987a,b). Later on, the associations between common DNA polymorphisms of apo B, and the immunogenetic polymorphisms detected with Ag and monoclonal antibodies were described (Berg et al. 1986, Ma et al. 1987, Ma et al. 1989, Wang et al. 1990. Xu et al. 1989, Dunning et al. 1991). Some of the studies carried out in Finland demonstrated associations between certain apo B polymorphisms and serum lipid levels, while some associations reported elsewhere were absent in Finnish individuals. We explored the possibility that variation at the apo B gene locus contributed to the common occurrence of hyperlipidemias and coronary heart disease (CHD) among the Finns.
Evidence for single gene contributions to hypertension and lipid disturbances: definition, genetics, and clinical significance
Authors: Williams Roger R. , Hunt Steven C. , Hopkins Paul N. , Wu Lily L , Lalouel Jean Marc
Published: July 2010

Several large family studies are reviewed to identify results suggesting single gene traits contributing to the occurrence of hypertension in humans. Segregation analysis in families has suggested major gene effects for several highly heritable traits associated with hypertension. These include recessively segregating high sodium‐lithium countertransport (major gene H2= 34%), additively segregating low urinary kallikrein excretion (major gene H2= 51%), and recessively segregating hyperinsulinemia (major gene H2= 33%). In some families, hypertension and metabolic abnormalities (dyslipidemia, hyperinsulinemia, and obesity) seem to be related to several candidate genes studied but not conclusively proven (LPL deficiency mutations, dense LDL subfractions, or NIDDM with hyperinsulinemia). More recently, DNA markers have identified genes promoting hypertension. Glucocorticoid‐remediable aldosteronism (GRA) promotes a rare but unusual form of hypertension that is unresponsive to ordinary medications but very responsive to glucocorticoid medications. GRA has been found in hypertensive persons with a specific mutation of the 11 beta‐hydroxylase gene on chromosome 8q21. Many persons with essential hypertension carry a common “susceptibility gene” at the angiotensinogen locus (chromosome lq4) identified using linkage studies in siblings, association studies, and in studies of preeclampsia and hypertension in pregnant women. These first two well‐established genetic loci promoting human hypertension represent two ends of a broad spectrum. The rare “determinant” gene for GRA by itself seems to produce severe hypertension and early strokes. The angiotensinogen (AGT) “susceptibility” gene is very common (30% of Utah Caucasians) and seems to predispose to hypertension but probably requires other genetic and environmental influences to be fully expressed. An understanding of other genetic and environmental factors that interact with genetic traits like angiotensinogen and kallikrein will probably identify patients in whom specific environmental interventions (such as sodium restriction or potassium supplementation) or specific types of medications will facilitate targeted prevention and treatment of hypertension and its complications.
Genetic markers in hypercholesterolemic and normocholesterolemic Czech children
Authors: Poledne Rudolf , Hubáček Jaroslav , Píša Zbyněk , Pistulková Helena , Valenta Zdeněk
Published: July 2010

The genetic background of polygenic hypercholesterolemia was studied in hypercholesterolemic children consuming a diet identical to control individuals with low cholesterol concentrations. Significantly higher frequencies of “disadvantage” alleles, usually combined with a higher LDL cholesterol, were found in hypercholesterolemic individuals when polymorphisms in apolipoprotein E, apolipoprotein B — XbaI and LDL receptor — PvuII were studied.
The angiotensin‐converting enzyme (ACE) genetic polymorphism: its relationship with plasma ACE level and myocardial infarction
Authors: Cambien Franĉois
Published: July 2010

The angiotensin‐converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin, two important peptides involved in vascular physiology. Plasma and cellular ACE levels in humans are influenced by an insertion (I)/deletion (D) polymorphism of the ACE gene, the ACE I/D polymorphism. The D allele has a frequency of approximately 0.53 in Caucasian populations and is codominantly associated with higher levels of ACE. We have studied this polymorphism in a large multicenter case‐control study (the ECTIM study) and found that the D allele was associated with a parental history of fatal myocardial infarction (MI) in the controls and was more frequent in male patients with MI than in controls. This case‐control difference was compatible with a codominant effect of allele D on the risk of MI with relative risks of 1.57 for DD vs II and 1.26 for ID vs II (test for trend p < 0.003). In subjects at low risk of MI (plasma ApoB < 1.25 g/1 and body mass index < 26 kg/m2), the relative risk of DD vs ID + II was 2.7 (p < 0.0005). The results were very homogeneous in the four populations included in the study. In a family study, using linkage‐segregation analysis, we have shown that the ACE I/D polymorphism is a marker for an unknown functional polymorphism (ACE S/s) which appears to be a new independent risk factor for MI.
DNA polymorphisms at the locus for human cholesteryl ester transfer protein (CETP) are associated with macro‐ and microangiopathy in non‐insulin‐dependent diabetes mellitus
Authors: Ukkola Olavi , Savolainen Markku J. , Salmela Pasi I. , von Dickhoff Kai , Kesäniemi Y. Antero
Published: July 2010

The effect of variation at the cholesteryl ester transfer protein (CETP) gene locus and in the apolipoprotein (apo) AI‐CIII‐AIV gene cluster on the susceptibility of individuals with non‐insulin‐dependent diabetes mellitus (NIDDM) to atherosclerotic vascular disease was studied in 136 male and 122 female patients with NIDDM. The prevalence of myocardial infarction was high (38%) in patients with the EcoNI genotype 2–2 of the CETP gene locus (= 2‐2; subjects homozygous for the absence of the restriction site) compared with patients with the genotype 1–1 (=1–1; subjects homozygous for the presence of the restriction site) (18%, p < 0.02). The prevalence of any evidence of coronary heart disease (CHD) (presence of ischaemic ECG changes or definite myocardial infarction) was high in 2–2 (73%) compared with the genotype 1–2 (= 1–2; heterozygous for the presence of the restriction site) (52%, p < 0.02) and genotype 1–1 (p = 0.06). CHD was more prevalent in men with 2–2 (70%) than in those with 1–1 (42%, p < 0.05), but in women no significant differences were found in the prevalences of CHD between the EcoNI genotypes. Neuropathy was more often present in the patients with 2–2 (31%) than in those with 1–1 (12%, p < 0.02) or 1–2 (14%, p < 0.01). Plasma total cholesterol and total‐ and VLDL‐triglycerides were higher in women with the EcoNI genotype 1–1 than in those with the genotype 1–2. In men no significant differences in plasma lipids were found. In addition, the prevalence of cerebrovascular disease was high (21%) in the patients with the genotype 1–1 of the TaqlB polymorphism compared with the genotype 2–2 (6%, p < 0.0–2). None of the alleles defined by four polymorphisms in the apo AI‐CIII‐AIV gene region were associated with an increased risk for macroangiopathy. The PstI polymorphism had an effect on plasma triglyceride levels. At the CETP locus one pair of loci (TaqlB and EcoNI) and three pairs of loci at the apo AI‐CIII‐AIV gene cluster (SacI and MspI, SapI and PvuII and MspI and PvuII) showed significant allelic association. In conclusion, the variation of CETP locus modulates the risk for diabetic complications in patients with NIDDM and the effect seems to be different between men and women. In contrast, the AI‐CIII‐AIV gene cluster polymorphisms seem not to be related to the risk of CHD in NIDDM. Long‐term follow‐up studies are needed to confirm the association of CETP gene polymorphism with diabetic complications.
Linkage between severe atopy and chromosome 11q13 in Japanese families
Authors: Shirakawa T. , Hashimoto T. , Furuyama J. , Takeshita T. , Morimoto K.
Published: July 2010

Atopy, characterised by allergic asthma and rhinitis, is due to increased IgE responses to common aeroallergens. An Oxford group has described maternal inheritance of atopy, where there is significant linkage between IgE responsiveness and a VNTR marker D11S97 and a CA microsatellite within a candidate gene, the high affinity IgE receptor β subunit(FcεRIβ), on chromosome 11q. Attempts at independent replication have produced conflicting results. We therefore recruited 270 atopic asthmatic probands in a Japanese community population for genetic linkage analysis. Four families, each with more than 15 meioses and a clear phenotype for atopy, were selected for genetic analysis. Atopy was defined as presence of all of raised total IgE, positive RAST and skin tests to three or more aeroallergens; non‐atopy, as absence of all these criteria. Linkage analysis showed a maximum two‐point lod score of 9.35 for D11S97 and FcεRIβ under the assumption of unequal rates of maternal and paternal recombination. Two families showed close genetic linkage with FcεRIβ with a pattern of maternal inheritance. These results from a Japanese population provide further evidence for genetic linkage between severe atopy and chromosome 11q13 and the likelihood of genomic imprinting at the locus.
A 12‐year preventive program for β‐thalassemia in Northern Sardinia
Authors: Longinotti M. , Pistidda P. , Oggiano L. , Guiso L. , Frogheri L. , Dore F. , Pardini S. , Bonfigli S. , Rimini E. , Angioni S. , Mulas P. , Inzaina A.
Published: July 2010

From 1980 to 1991, 6.3% of the adult population of the province of Sassari, Northern Sardinia, underwent voluntary β‐thalassemia screening. Of the 28 000 subjects examined, 15.7% proved to be heterozygotes for β‐thalassemia. In addition, the screening of 7500 students in 26 villages in Sassari province fixed the frequency of β‐thalassemia in this part of Sardinia at 10.4%. Of the 539 couples at risk to be expected from this figure, the screening detected 43% (234). The data suggest that inductive screening played a major role in the efficiency of this preventive β‐thalassemia program. Follow up of 221 pregnancies found to be at risk for homozygous β‐thalassemia and referred to the Antenatal Diagnosis Service, Cagliari, Southern Sardinia, showed that antenatal diagnosis was carried out in 80% of them. The overall percentage of couples refusing antenatal diagnosis was 10.8%, but over the years the acceptance rate for the procedure increased from 87% to 96%. Atypical hematological findings in 1.5% of 468 members of the couples at risk required globin chain synthesis and molecular analyses to define the precise β‐thalassemia genotype. Heterogeneous “mild”β‐thalassemia mutations as well as coexisting δ‐thalassemia were found in silent type I and type II β‐thalassemia carriers which, without chain synthesis and DNA investigations, would have escaped detection.
Complex chromosomal rearrangements: some breakpoints may have cellular adaptive significance
Authors: Lurie Iosif W. , Wulfsberg Eric A. , Prabhakar Gayathri , Rosenblum‐Vos Lynne S. , Supovitz Karen R. , Cohen Maimon M.
Published: July 2010

Cytogenetic study of a 3‐year‐old girl with developmental delay and some minor abnormalities revealed a complex chromosome rearrangement (CCR) involving seven chromosomes with eight breakpoints, leading to monosomy of segment 5q15‐q22. According to breakpoint distribution, CCRs may be classified as those with primary intrachromosomal abnormalities (including inversions, insertions, duplications, etc.) and those without them. Only the latter group of CCRs was used in this analysis. Comparison of theoretical and observed breakpoint distributions in 33 cases demonstrated that recurrent involvement of some chromosome(s) (“re‐entry”) occurs more frequently than expected. One possible explanation for this observation suggests that the initial event leads to an unstable provisional rearrangement, and subsequent breaks are necessary to stabilize the karyotype.
Possible localization of a major gene for cleft lip and palate to 4q
Authors: Beiraghi S. , Foroud T. , Diouhy S. , Bixler D. , Conneally P. M. , Delozier‐Blanchet D. , Hodes M. E.
Published: July 2010

Two of the 13 PCR markers were most informative in tentatively identifying a major gene for cleft lip on the q arm of chromosome #4 with a maximum LOD score of 2.27 (Ø= 0)
Exclusion of linkage to 14q23‐24 in a family with Holt‐Oram syndrome
Authors: Ruiz Juan Carlos , Legius Eric , Cuppens Harry , Moens Pierre , Marynen Peter , Cassiman Jean‐Jacques
Published: July 2010

Holt‐Oram syndrome is an autosomal dominant disorder with congenital heart defects and skeletal malformations of the upper extremities. A patient with a deletion of 14q23‐24 and Holt‐Oram syndrome has been described. In this report, however, genetic linkage to the 14q23‐24 region is excluded in a multigeneration family with five available individuals affected with Holt‐Oram syndrome. Familial Holt‐Oram syndrome might be different from the syndrome with the 14q23‐24 deletion.
Single mandibular incisor in a patient with del (18p) anomaly
Authors: Pfeiffer R. A. , Hertrich K. , Cohen M.
Published: July 2010

A single mandibular incisor and an unusually narrow mandible and tongue were noted in an 8‐year‐old moderately retarded boy with 18p‐ (45, XY, der dic (18) (18qter‐p11.2::22p 11.2‐qter). While a single maxillary incisor, considered a minor feature of holoprosencephaly, was reported in three cases of 18p‐, reduction of mandibular incisors has been a very rare finding and has never been noted in similar cases.
No effect on blood pressure level or variability of polymorphisms in DNA at the locus for atrial natriuretic factor (ANF)
Authors: Berge K. E. , Berg K.
Published: July 2010

We have examined healthy Norwegians with respect to two restriction fragment length polymorphisms at the locus for atrial natriuretic factor, detectable with the restriction enzymes XhoI and BglI, respectively. No association with systolic or diastolic blood pressure level or variability was found. Thus, the normal genes detected by examination of these restriction fragment length polymorphisms have neither “level gene” nor “variability gene” effects on normal blood pressure.
Plasma lipids and lipoproteins response to a dietary challenge: analysis of four candidate genes
Authors: Friedlander Yechiel , Berry Elliot M. , Eisenberg Shlomo , Stein Yechezkiel , Leitersdorf Eran
Published: July 2010

The possible role of four candidate genes in lipid and lipoprotein response to diet was examined in 63 male students. Four site polymorphisms (signal peptide insertion/deletion, XbaI, MspI and EcoRT) of the apo B gene, three RFLPs (AvaII, StuI, and HincII) of the LDL receptor gene, two SSCPs of the cholesterol 7α‐hydroxylase gene and the common apo E genotypes were determined. The average reductions induced by diet in participants homozygous for the absence of the XbaI restriction site (X—X—) of the apo B gene compared to those harboring this site (X+) were: 14.5 mg/dl and 9.4 mg/dl for total cholesterol (TC) (p<0.09) and 15.5 mg/dl and 7.9 mg/dl for LDL‐C (p<0.003), respectively. Differences in dietary responsiveness among the apo E, LDL receptor and the cholesterol 7α‐hydroxylase genotypes were largely insignificant. Using the four apo B polymorphic sites, six unambiguous haplotypes were constructed and a model for their possible evolutionary relationship is presented. Genetic variation in the apo B gene region, as defined by haplotypes, accounted for 8.7% and 24.3% of the phenotypic variance in TC and LDL‐C response to diet, respectively. Sequence analysis of a candidate locus, the putative LDL receptor binding region of apo B and its flanking sequences, was performed in two individuals, one homozygous for an apo B “hyper‐responding” and another for the “lower‐responding” haplotype, and no differences were found. In conclusion, haplotypes at the apo B gene locus are associated with dietary response of TC and LDL‐C in young males. Yet, the sequence variation responsible for these differences is possibly located outside the putative LDL receptor binding domain.
Familial microcephaly with severe neurological deficits: a description of five affected siblings
Authors: Gross‐Tsur V. , Joseph A. , Blinder G. , Amir N.
Published: July 2010

Autosomal recessive microcephaly is usually characterized by normal developmental milestones and minor neurological deficits. In this report, we describe five siblings in one family with marked microcephaly, intractable seizures, quadriplegia and profound mental retardation. The recurrence risk of microcephaly when associated with devastating neurological deficits, as exemplified by this family, may be high and in such cases, the role of appropriate genetic counseling is of utmost importance.
Sperm chromosome complements in a man heterozygous for a reciprocal translocation 46,XY,t(9;13)(q21.1;q21.2) and a review of the literature
Authors: Martin Renée H. , Spriggs Elizabeth L.
Published: July 2010

Sperm chromosome complements were studied in a man heterozygous for a reciprocal translocation t(9;13)(q21.1;q21.2). A total of 89 spermatozoa were karyotyped after in vitro penetration of hamster eggs. The frequencies of alternate, adjacent 1 and adjacent 2 segregations were 46.9%, 35.8% and 17.3% respectively. For alternate segregation, the number of normal spermatozoa (21) was not significantly different from the number of spermatozoa carrying a balanced form of the translocation (17), as theoretically expected. The proportion of spermatozoa with an unbalanced form of the translocation was 53.1%. There was no evidence for an interchromosomal effect since the frequency of numerical abnormalities (unrelated to the translocation) was within the normal range of control donors. Data from a total of 31 reciprocal translocations studied by sperm chromosomal analysis were reviewed.
Congenital cardiac malformations in Adams‐Oliver syndrome
Authors: Zapata Hugo H. , Sletten Lisa J. , Pierpont Mary Ella M.
Published: July 2010

Two patients with Adams‐Oliver syndrome and congenital cardiac malformations are described. A literature review revealed a 13.4% occurrence of congenital cardiac malformations in individuals with Adams‐Oliver syndrome, suggesting that cardiac anomalies are a frequent manifestation of this syndrome. All patients with Adams‐Oliver syndrome (aplasia cutis congenita and terminal digital anomalies) should be evaluated for cardiac anomalies.
Quantitation of fibrillin immunofluorescence in fibroblast cultures in the Marfan syndrome
Authors: Schaefer G. Bradley , Godfrey Maurice
Published: July 2010

The Marfan syndrome (MFS) is a heritable connective tissue disorder manifested by defects in the skeletal, ocular, and cardiovascular systems. Diagnosis of MFS is based on clinical findings. At present there are no laboratory tests for specific determination of this disorder. Defects in fibrillin, an elastin‐associated microfibrillar glycoprotein, are now known to cause the variable and pleiotropic manifestations of MFS. Immunofluorescence studies of skin sections and dermal fibroblast cultures were the first to show this association. Most unequivocal cases of the Maffan syndrome exhibited an apparent reduction in fibrillin immunofluorescence. The prospect of examining patients whose clinical findings suggest a possible diagnosis of the Marfan syndrome has stimulated us to attempt quantitation of immunofluorescence. In the study described here we used computer‐enhanced image analysis to establish “normal” and “abnormal” (Marfan) parameters of fibrillin immunofluorescence in dermal fibroblast cultures. Quantitation of fluorescence from control individuals showed a median of 21%, while the median fibrillin fluorescence in MFS patients was 6% with a confidence interval of 15%. These findings were statistically significant to p<0.01. It is hoped that these analyses may become a useful adjunct in the clinical diagnosis of MFS.
Cytogenetic analysis of 23 Japanese patients with amyotrophic lateral sclerosis
Authors: Kaneko Kiyotoshi , Saito Fumiko , Sunohara Nobuhiko , Ikeuchi Tatsuro
Published: July 2010

The cytogenetic analysis of 23 Japanese patients with amyotrophic lateral sclerosis is reported. G‐banded chromosomes of cultured peripheral blood lymphocytes of one subject had a constitutional chromosomal translocation, t(7;13)(p22;q21). No constitutional chromosome abnormality was found in any of the other 22 Japanese patients with amyotrophic lateral sclerosis tested.
Triosephosphate isomerase deficiency: biochemical and molecular genetic analysis for prenatal diagnosis
Authors: Pekrun A. , Neubauer B. A. , Eber S. W. , Lakomek M. , Seidel H. , Schröter W.
Published: July 2010

Inherited deficiency of the glycolytic enzyme triosephosphate isomerase leads to a multisystem disorder characterized by progressive neuromuscular dysfunction, chronic nonspherocytic hemolytic anemia and increased susceptibility to severe infections. Most patients die within the first 6 years. We examined a family with severe triosephosphate isomerase deficiency. The 1‐year‐old index patient suffered from hemolytic anemia, neuromuscular impairment and pneumonias, with the necessity of intermittent mechanical ventilation. Triosephosphate isomerase activity in erythrocytes was reduced to about 20% of normal. Heat stability of the enzyme was strongly reduced; concentration of the physiological substrate, dihydroxyacetone phosphate was increased 20‐fold due to the metabolic block. Direct sequencing of the triosephosphate isomerase gene revealed homozygosity for the formerly described GAGGAC‐mutation changing 104 GluAsp. During a 2nd pregnancy we examined a cord blood sample obtained in the 19th gestational week. The biochemical data on enzyme activity, heat stability of the enzyme and concentration of dihydroxyacetone phosphate were in the normal range. The molecular genetic analysis confirmed the presence of the normal triosephosphate isomerase alleles. Pregnancy was continued, resulting in the delivery of an unaffected, healthy newborn.
Familial hypertryptophanemia in two siblings
Authors: Martin John R. , Mellor Clive S. , Fraser F. Clarke
Published: July 2010

Mild and moderate mental retardation with exaggerated affective responses, periodic mood swings, and apparent hypersexual behavior were present in two siblings with hypertryptophanemia and tryptophanuria. In addition, the male had severe myopia, a speech impediment, musculo‐skeletal abnormalities and perceptual hypersensitivity. His sister was deaf, which was ascribed to antenatal rubella. The occurrence in siblings and the presence of abnormal urinary tryptophan metabolites in the mother and a half‐sibling suggest that the condition results from an autosomal recessive gene with minor expression in some heterozygotes.
Restriction fragment length polymorphisms at the apoprotein genes AI, CIII and B‐100 and in the 5‘ flanking region of the insulin gene as possible markers of coronary heart disease
Authors: Wick Ursula , Witt Erwin , Engel Wolfgang
Published: July 2010

Several sequence variations were examined for being endogenous “risk markers” in the development of CHD. The “markers” in this study included: the PstI‐SstI RFLPs in the apo AI‐CIII gene cluster, the EcoRI‐MspI RFLPs in the apo B100 gene and the SstI RFLP in the 5‘ flanking region of the insulin gene. The study population comprised 700 individuals of German origin. A strong association of these “markers” to the disease phenotype predicts their loss in healthy individuals with ages above that of the prevalent incidence of CHD. In contrast, these “markers” should accumulate in diseased persons. A significant age‐dependent selection was observed for the EcoRI RFLP in the apo B100 gene. This was the case when the allele and genotype frequencies of healthy old individuals were compared with those of newborns. In contrast, no RFLP showed significant differences in allele and genotype distributions between patients defined by coronary angiography and controls. In the group of patients, but not controls, several RFLP genotypes were found to be associated with significantly higher serum levels of cholesterol and triglycerides. This was true in the case of serum cholesterol comparing the genotypes S1S2 with those of S1S1 (p=0.05) observed for the SstI polymorphic site in the 3’ noncoding region of the apo CIII gene. Significantly higher levels of triglycerides were found within the heterozygous patients P1P2 (p=0.045) and S1S2 (p=0.02) than in the homozygotes P1P1 and S1S1 for the PstI‐SstI RFLPs at the apo AI‐CIII gene cluster. The SstI RFLP in the 5‘ flanking region of the insulin gene also revealed significantly higher values of triglycerides among the patients with the genotype UU compared to the heterozygotes LU (p=0.005) and to the homozygotes LL (p=0.0008). Among the patients, the combined genotype P1P2 S1S2 for the PstI‐SstI RFLPs at the apo AI‐CIII genes first had higher serum cholesterol levels than the genotype P1P2 S1S1 (p=0.02) and secondly had higher values of serum triglycerides compared to the genotypes: P1P1 S1S1 (p=0.01), P1P2 S1S1 (p=0.02) and P1P1 S1S2 (p=0.03).
Inter‐ and intrafamilial variability in mucolipidosis II (I‐cell disease)
Authors: Beck M. , Barone R. , Hoffmann R. , Kratzer W. , Rakowsky Th. , Nigro F. , Fiumara A.
Published: July 2010

In this paper nine patients with mucolipidosis II (I‐cell disease) are described. They had clinical features commonly found in mucolipidosis II, including disproportionate dwarfism, coarse facial features and mental retardation. However, there was remarkable variability in age of onset, organ manifestation and radiological findings. Some had unusual clinical symptoms including pericardial effusion and profound brain atrophy. Striking differences in phenotypic expression were also seen in two affected siblings. Clinical heterogeneity is observed not only in mucolipidosis II but also in many other lysosomal storage disorders. The factors that may contribute to this clinical diversity are discussed.
Periumbilical skin length measurements in the newborn
Authors: Toppare Mete F. , Kitapci Füsun , Dilmen Uǧur , Kaya I. Safa , Şenses Dursun A.
Published: July 2010

Normal limits of periumbilical skin were determined in 304 newborn babies in the first 24 h. Cranial umbilical skin (SD) was 12.36 (3.23) mm and caudal umbilical skin (SD) was 8.76 (3.10) mm on the average. It is recommended that cranial umbilical skin measurement should be included in the examination of dysmorphic neonates, and those with cranial skin length above 18.82 mm (>2 SD) should be carefully evaluated for Rieger syndrome.
New familial association between ocular coloboma and loose anagen syndrome
Authors: Murphy M. F. , McGinnity F. G. , Allen G. E.
Published: July 2010

We present two cases of loose anagen syndrome associated with ocular coloboma in two siblings of unaffected parents and with no family history. We believe they represent a new familial association between these two conditions.
Genetic analysis of 20 families with autosomal dominant adult polycystic kidney disease from South West Thames Region
Authors: Jeffery S. , Saggar‐Malik A. K. , Morgan S. , Eastwood J. B. , Patton M.
Published: July 2010

Twenty families with autosomal dominant polycystic kidney disease from S.W. Thames Region were analysed using markers for chromosome 16p13.3, the site of the common mutation (PKD1). Six families gave a negative lod‐score for 3'HVR, the most informative distal marker. This could be explained in four cases by recombination events. Of the two families where this was not an explanation, one, of Italian origin, was unequivocally unlinked for all markers, and the other was more likely to be non‐PKD1 than linked to 16p13.3. The Italian family was ascertained through the Blood Pressure Unit, and the other via the Genetic Clinic. No members of either family had ever attended a renal clinic. The remaining 18 families either came via renal clinics, or had at least one member attending such a centre.