bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotype analysis in cystic fibrosis in relation to the occurrence of diabetes mellitus
Authors: Hamdi I. , Payne S. J. , Barton D. E. , McMahon R. , Green M. , Shneerson J. M. , Hales C. N.
Published: July 2010

Carbohydrate intolerance and frank diabetes mellitus (DM) are recognised features of cystic fibrosis (CF), but their cause has not been established. Damage to the islet cells due to pancreatic fibrosis is the most common explanation. The relationship between the genotype and the occurrence of diabetes mellitus has been examined in 21 cystic fibrosis patients attending our out‐patient chest clinics. DNA samples were tested for the presence of the most common mutation (AF508) and the results related to the degree of carbohydrate intolerance. We found that in CF patients over 18 years of age diabetes is more frequent among those homozygous for the AF508 allele than the heterozygotes (P < 0.05). Those homozygous for AF508 were diagnosed as CF at an earlier age than the heterozygotes (P < 0.05). Both the mean age and the female/male ratio were similar in the diabetic and non‐diabetic groups. The prevalence of the AF508 allele was similar to that expected in a random sample of East Anglian cystic fibrosis patients. These data suggest that the occurrence of diabetes mellitus in patients with cystic fibrosis is related to the genotype, which could be secondary to the way the genetic factors influence the degree of pancreatic disease and its rate of progression.
Defective G2 repair in Down syndrome: effect of caffeine, adenosine and niacinamide in control and X‐ray irradiated lymphocytes
Authors: Pincheira J. , Rodriguez M. , Bravo M. , Navarrete M. H. , Lopez‐Saez J. F.
Published: July 2010

Lymphocytes from both Down syndrome (DS) patients and age‐matched control donors have been investigated to identify a possible disturbance in chromosomal G2 repair. Analyses of caffeine treatments during G2 have shown that the frequency of chromosomal aberrations is higher in DS lymphocytes than in normal lymphocytes. Likewise, G2 duration is longer in DS cells than in normal cells. In both control and DS lymphocytes, caffeine treatments increase the frequencies of chromatid breakages and decrease the average of G2 duration. The reversal of the caffeine potentiation effect by adenosine and niacinamide is higher in DS cells than in normal cells. Furthermore, ATP content per cell in DS lymphocytes is one third of that estimated in normal lymphocytes. The increase of ATP level produced by adenosine or niacinamide generally correlates with the reversal of the caffeine effect on chromosome aberrations. Under the experimental conditions tested, a good negative exponential correlation between ATP level and chromosome aberrations has been detected in both normal and DS lymphocytes which were or were not X‐irradiated. Finally, we postulate a decrease in G2 repair capability of DS lymphocytes caused by a low availability of ATP and/or some other factor correlating with it.
Direct transmission of a tandem duplication in the short arm of chromosome 8
Authors: Dhooge C. , Roy N. Van , Craen M. , Speleman F.
Published: July 2010

A family is described in which a mother and her two children carry a tandem duplication of the short arm of chromosome 8. Their phenotypes are similar and characterised by distinct facial dysmorphism, small stature and mild mental retardation. This is one of the first cases of direct familial transmission of a partial duplication of an autosomal chromosome segment.
A fluorescentin situhybridization analysis of the chromosome constitution of ejaculated sperm in a 47, XYY male
Authors: Han Tie Lan , Ford Judith H. , Flaherty Sean P. , Webb Graham C. , Matthews Colin D.
Published: July 2010

Two semen samples from a 47, XXY male were examined using chromosome‐specific DNA probes and fluorescentin situhybridization (FISH) to determine the distribution of sex chromosomes and an autosome (chromosome 17) in the sperm. A motile population of sperm was also prepared from one sample using the swim‐up technique to compare the motile and total sperm populations. Chromosomes were localized using single FISH and a biotinylated chromosome 17 probe (TR17), or double FISH using a biotinylated X chromosome probe (TRX) and a digoxigenin‐labelled Y chromosome probe (HRY). Labelling efficiencies were 95–98%. Ploidy levels were estimated by measurement against a microscope eyepiece graticule. The overall ratio of X‐to Y‐bearing sperm was 47% to 48.4% in the neat samples, and 48.4% to 45.3% in the swim‐up fraction. Neither of the ratios was significantly different from 1:1. The frequencies of monosomic and disomic (but otherwise haploid sperm) were not different from the frequencies we observed in normal donors. In contrast, the frequencies of both diploid and tetraploid cells were increased in the neat samples of the XYY male. In the swim‐up fractions, however, none of these parameters differed from those of ten normal semen donors. These results support the hypothesis that the extra Y chromosome in XYY men is eliminated during spermatogenesis.
Duchenne muscular dystrophy and spinal muscular atrophy type I segregating in the same family
Authors: Oldfors Anders , Martinsson Tommy , Tessin Ingemar , Wahlström Jan , Wang Shu
Published: July 2010

We report on a family with two severe neuromuscular diseases: Duchenne muscular dystrophy (DMD) and acute infantile spinal muscular atrophy (SMA I). One boy has DMD, and his brother died of SMA I at 11 months of age. Both boys had received the same DMD allele from their mother. Analysis of dystrophin by immunohistochemistry and Western blot showed complete lack of dystrophin in both brothers. The mother had a partial deficiency of dystrophin. The boy with SMA I had increased levels of creatine kinase in serum, compatible with DMD, but the muscle biopsy and post‐mortem examination of the spinal cord showed the typical changes of SMA I. There were no cytogenetic abnormalities explaining the occurrence of both DMD and SMA I in this family. Molecular genetic prenatal diagnosis of DMD and SMA I, using analysis of RFLPs and dinucleotide repeats, has been performed in one foetus in the family. The results showed that the foetus had a high risk of developing SMA I. An abortion was planned but the pregnancy was terminated by miscarriage.
Non‐expression of von Hippel‐Lindau phenotype in an obligate gene carrier
Authors: Davies D. R. , Norman A. M. , Whitehouse R. W. , Evans D. G. R.
Published: July 2010

Von Hippel‐Lindau disease is generally considered to be a condition with very high penetrance, and individuals who live beyond the age of 60 years without showing any features of the disease, despite undoubtedly carrying the gene defect, have not previously been clearly described. The case is presented of a 65‐year‐old woman, who had four siblings affected with von Hippel‐Lindau disease and had six children, three of whom died young with complications of von Hippel‐Lindau disease. Although she is an obligate gene carrier, she has not developed any significant manifestations of the disease despite careful screening for the neurological, retinal and renal complications.
Oto‐palato‐digital syndrome type II in two unrelated boys
Authors: Preis Sabine , Kemperdick H. , Majewski F.
Published: July 2010

We report on two boys with oto‐palato‐digital syndrome type II, characterized by growth retardation, bowed long bones, missing or hypoplastic fibulae, sclerosis of the skull base and wavy, irregular clavicles and ribs. The facial appearance is distinctive due to prominent forehead, widely spaced eyes, antimongologid slant of palpebral fissures, flattened nasal bridge and retrogenia. The mother of one patient showed a mild manifestation of oto‐palato‐digital syndrome type II. Only about 20 cases of this rare X‐linked disorder have been reported so far. The similiarities and dissimilarities to oto‐palato‐digital syndrome type I are discussed.
Clinical aspects of the MASA syndrome in a large family, including expressing females
Authors: Kaepernick L. , Legius E. , Higgins J. , Kapur S.
Published: July 2010

We have evaluated, both clinically and by linkage analysis, a large family with 22 known affected males with the MASA syndrome (McKusick 303300). Clinical findings varied widely amongst the affected family members, with some appearing initially to have the MASA syndrome and others to have X‐linked hydrocephalus (HSAS) (McKusick 307000). Important findings included the presence of adducted thumbs in two obligate carriers, learning problems or mild mental retardation in three females, two of whom were obligate carriers, and hydrocephalus with neonatal death in three females born to obligate carriers. X‐inactivation analysis in lymphocytes from the two women with adducted thumbs revealed preferential inactivation of one X chromosome, suggesting that nonrandom X‐inactivation may be responsible for clinical expression in females. The presence of HSAS in some individuals of this family and the MASA syndrome in others further supports the hypothesis that these two conditions are the result of a mutation in the same gene.
Partial trisomy and monosomy 8p due to inversion duplication
Authors: Engelen J. J. M. , de Die‐Smulders C. E. M. , Fryns J. P. , Hoovers J. M. N. , Albrechts J. C. M. , Loots W. J. G. , Jacobs M. E. , Hamers A. J. H.
Published: July 2010

Fluorescent in situ hybridization with probes specific for a chromosomal subregion and chromosome‐specific libraries (chromosome painting) are important new methods for assessing chromosome rearrangements. In this paper we present four patients with additional chromosomal material on chromosome 8p who have been studied using G‐banding techniques, chromosome painting and FISH with cosmid probes specific for the region 8p23.1 → 8pter. In all cases we found a partial inversion duplication of 8p along with a deletion of the region 8p23.1 → 8pter.
Gaucher disease: N370S glucocerebrosidase gene frequency in the Portuguese population
Authors: Lacerda L. , Amaral O. , Pinto R. , Oliveira P. , Aerts J. , Miranda M. C. Sá
Published: July 2010

In the Portuguese population the most frequent form of Gaucher disease is type 1. The N370S glucocerebrosidase gene mutation accounts for 63% of mutated alleles. The frequency of this mutation was accurately determined in the Portuguese population, which does not present an Ashkenazi Jewish genetic background. A gene frequency of 0.0043, with 95% confidence limits between 0.0023 and 0.0063, was obtained studying the genomic DNA of 2000 blood cards randomly sampled from the national neonatal screening program. On the basis of this frequency a significantly high number of homozygotes for the N370S mutation should be expected in the Portuguese population. This finding supports the idea that the majority of homozygotes for this mutation present a very mild clinical phenotype and remain undiagnosed.
The apolipoprotein B signal peptide insertion/deletion polymorphism is not associated with myocardial infarction in Norway
Authors: Bøhn M. , Bakken A. , Erikssen J. , Berg K.
Published: July 2010

The three‐amino acid insertion/deletion (I/D) polymorphism in the apoB signal peptide (27 amino acid versus 24 amino acid signal peptide) was evaluated as a possible risk factor for myocardial infarction (MI) in a case‐control study population comprising 238 MI survivors and 547 controls. In controls, homozygotes for the deletion allele (DD) had the highest mean levels of both total cholesterol and low density lipoprotein (LDL) cholesterol (LDLC), the homozygotes for the insertion allele (II) had the lowest mean values, while the heterozygotes (ID) had intermediate mean levels (p < 0.05). In MI survivors, the trend was similar, but only differences in mean LDLC levels were statistically significant (p < 0.05). No differences in genotype frequencies were detected between cases and controls in univariate analysis or in multivariate logistic regression analysis. Despite the results from the lipid analyses, we conclude that the I/D polymorphism in the apoB signal peptide is unlikely to be of major importance for MI risk in relatively young Norwegians.
Molecular and clinical analyses of cystic fibrosis in the South of Spain
Authors: Borrego Salud , Casals Teresa , Dapena Javier , Fernández Esther , Giménez Javier , Cabeza Juan C. , Sánchez Javier , Antiñolo Guillermo
Published: July 2010

We report molecular and clinical analyses in 71 unrelated patients with cystic fibrosis (CF) from Andalusia (South of Spain). Direct mutation analysis of six mutations of the CFTR gene (ΔF508, G542X, R1162X, N1303K, W1182X and 1949del84) was performed. The proportion of CF chromosomes with the above‐mentioned mutations was 58.5%. Haplotype analysis was performed with the marker/enzyme pairs XV2C/TaqI and KM19/PstI. A particular haplotype has been found associated with each of the studied mutations, while the pooled data for the unknown mutations are not associated with any particular haplotype. This lack of association indicates that there will not be a single predominant mutation amongst the other CF chromosomes. To assess the relationship between genotype and phenotype in these patients, we correlated the pancreatic status and the occurrence of chronic Pseudomona aeruginosa infection with the observed genotype. Pancreatic insufficiency was present in all patients in whom the analyzed mutations were found to be homozygous or compound heterozygous. We also found a higher rate of Pseudomonas colonization in the group of patients in whom the genotype was homozygous or compound heterozygous for the analysed mutations when compared with the group of patients with a different genotype, but the difference was not statistically significant.
Charcot‐Marie‐Tooth disease type 1A: the parental origin of a de novo 17p11.2‐p12 duplication
Authors: Hertz Jens Michael , Børglum Anders D. , Brandt Carsten A. , Flint Tracey , Bisgaard Carsten
Published: July 2010

Charcot‐Marie‐Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a DNA duplication on chromosome 17p11.2‐p12 in the majority of cases. Most of the sporadic cases are due to a de novo duplication. We have screened for this duplication in 11 Danish patients with CMT type 1, using four different techniques, and identified a de novo duplication in a sporadic case. Analysis of the fully informative pVAW409R3a alleles in this family showed the duplication to be of paternal origin.
X;1 translocation in a female Menkes patient: characterization by fluorescence in situ hybridization
Authors: Beck James , Enders Herbert , Schliephacke Martin , Buchwald‐Saal Monika , Tümer Zeynep
Published: July 2010

Menkes disease is an X‐linked recessive disorder of copper metabolism, characterized by progressive neurological degeneration, abnormal hair and connective tissue manifestations. We present a female Menkes patient, with classical Menkes features, carrying a de novo balanced translocation 46, X, t(X;1)(q13;q12). The breakpoint on the X chromosome was narrowed down to Xq13.3 within a 1 Mb YAC contig containing the Menkes gene, using fluorescence in situ hybridization. The translocated X chromosome was of paternal origin and non‐randomly active leading to the expression of the disease. This was additional evidence for paternal origin of de novo chromosome rearrangements, including all the X; autosomal translocations examined so far.
Familial translocation t(10;14) (q26.1;q32.3): report of three offspring with 10q deletion and 14q duplication
Authors: Huang Tim H.‐M. , Peckham Diane , Batanian Jacqueline R. , Martin Matthew B. , Kouba Melissa , Caldwell Charles W. , Miles Judith H.
Published: July 2010

We describe two brothers and a cousin with common clinical features, including mild mental retardation, motor delays, hypotonia with truncal ataxia, esotropia, and mild facial and hand dysmorphia. The initial routine chromosome study failed to detect any abnormality in the proband. Based on a high index of clinical suspicion, high‐resolution chromosome studies were performed on the proband's parents. A small reciprocal translocation t(10;14) (q26.1;q32.3) was detected in the father. The breakpoint on the derivative chromosome 14 was further placed telomeric to the immunoglobulin heavy‐chain gene cluster at the band q32.33 by fluorescence in situ hybridization. Studies of the proband and two affected paternal cousins revealed that each had inherited the same derivative chromosome 10 from their carrier parents. This unbalanced karyotype resulted from an adjacent‐1 segregation of the 10;14 translocation.
Oligodontia, short stature and small head circumference with normal intelligence
Authors: Melamed Yair , Katznelson Mariasa Bat‐Miriam , Frydman Moshe
Published: July 2010

Complete absence of third molars and mandibular permanent second molars is reported in a 19‐year‐old female, with occipito‐frontal head circumference and height at the 3rd centile. The patient's intelligence, appearance and physical examination were normal. Direct count of the patient's sweat pores in different areas of the palms and digits was normal. Microcephaly, short stature and normal intelligence have been reported in two families as a distinct autosomal dominant syndrome. To the best of our knowledge, oligodontia, in addition to these findings, has not been previously reported.
Short tarsus — absence of lower eyelashes: an autosomal dominant condition
Authors: Lopes Vera Lúcia Gil da Silva , Marques‐de‐Faria Antonia Paula , Sanches Valéria Elisabete , Caldato Roberto , Gorlin Robert J.
Published: July 2010

We describe a four‐generation Brazilian family with short tarsus and absence of the lower eyelashes, with normal intelligence. Autosomal dominant inheritance is evident.
A de novo 6q11—q15 duplication investigated by chromosome painting
Authors: Giardino D. , Rizzi N. , Briscioli V. , Bettio D.
Published: July 2010

A de novo interstitial duplication of the 6q11—q15 chromosome region, confirmed by the application of a chromosome 6 painting probe, was observed in a patient with craniofacial dymorphism, psychomotor retardation, cryptorchidism and hypospadias. Despite the publication of several cases showing partial trisomy 6q, to our knowledge the duplication of the proximal region q11‐q15 has not previously been reported.
Heredity in dementia of the Alzheimer type
Authors: Bergem A. L. Mina
Published: July 2010

Family, twin and linkage studies in Alzheimer's disease are reviewed. Several of these studies appear to be burdened with sources of error, mainly related to sampling and clinical diagnoses. It was previously thought that early‐onset cases of Alzheimer's disease were heavily genetically influenced, whereas late‐onset cases were sporadic. The author questions whether this difference is mainly due to methodological error.
Clinical features and natural history of Beckwith‐Wiedemann syndrome: presentation of 74 new cases
Authors: Elliott Margaret , Bayly Rosemary , Cole Trevor , Temple I. Karen , Maher Eamonn R.
Published: July 2010

Beckwith‐Wiedemann syndrome (BWS) is a congenital overgrowth syndrome with variable expression. To define the range and frequency of complications in BWS, we have studied a cohort of 76 affected patients (two previously reported). The most frequent complications were microglossia (97%), abdominal wall defect (80%) and birth weight or postnatal growth > 90th centile (88%). Other common features were ear creases/pits (76%), facial naevus flammeus (62%), nephromegaly (59%) and hypoglycaemia (63%). Rarer complications included hemihypertrophy (24%), moderate/severe developmental delay (4%), congenital heart defects (6.5%), polydactyly (4%), neoplasia (4%) and cleft palate (2.5%). Pre‐term labour occurred in 53% and polyhydramnios in 33% of BWS pregnancies. The six deaths all occurred in babies born pre‐term, three of whom had major congenital abnormalities. Five patients (6.5%) from four kindreds had an unequivocal family history of BWS, but 15 of 68 apparently sporadic cases had a relative with possible BWS (minor features only). Incomplete penetrance may lead to familial BWS being underdiagnosed.
Osteoarthropathia psoriatica of one leg: a manifestation of somatic mosaicism?
Authors: Holzmann Hans , Schmitt Markus , Happle Rudolf , Kaltwasser Peter , Hör Gustav
Published: July 2010

A psoriatic osteoarthropathy localized in the left quadrant of a male patient is described. Diagnosis was made on the basis of bone scintigraphy (specific distribution pattern) and histological evaluation of a bone biopsy. There is no indication of psoriasis in the patient's family. Nor is there an association to psoriasis‐typical HLA markers. Psoriasis of the skin has not been found. Environmental factors, including a Köbner phenomenon on the skeleton resulting from a trauma 13 years ago (hallux rigidus operation), are discussed in connection with this manifestation. The genetic aspects of this unusual localization are considered.
The influence of genetic counselling in the era of DNA testing on knowledge, reproductive intentions and psychological wellbeing
Authors: Rona R. J. , Beech R. , Mandalia S. , Donnai D. , Kingston H. , Harris R. , Wilson O. , Axtell C. , Swan A. V. , Kavanagh F.
Published: July 2010

Subjects of reproductive age at risk of having an affected child with a severe single gene disorder such as Duchenne muscular dystrophy (DMD) or cystic fibrosis (CF) were surveyed to ascertain: their views on genetic counselling and antenatal testing; their knowledge of their risk of having an affected child; and their psychological wellbeing. Questionnaires were posted to 209 individuals at 130 addresses; a 65% response rate was achieved. The majority of those surveyed were under 40 years of age (91%), half of them had received genetic counselling only once and for 47% the first encounter was after the diagnosis of their affected child. Most patients expressed their intention to use prenatal testing. However, less than 50% of those counselled knew their risk of having an affected child. Knowledge of risk was associated with the type of disease in the family (p<0.001) (inheritance of DMD was poorly understood by relevant subjects) and was positively associated with the participant's level of education (p<0.05). We did not detect a significant association between the number of intended children and the risk of having an affected child. In terms of family relations, genetic counselling appears to be beneficial for the nuclear family, the couple and their children, but some counsellees reported a detericration in relations with other relatives. The results indicate that couples at risk of having a child with a severe genetic disorder value the counselling provided, but many of them do not remember important facts in relation to their risk status.
DNA polymorphisms of human apolipoprotein A‐IV gene: frequency and effects on lipid, lipoprotein and apolipoprotein levels in a French population
Authors: Zaiou Mohamed , Visvikis Sophia , Gueguen René , Parra Henri‐Joseph , Fruchart Jean Charles , Siest Gérard
Published: July 2010

Genetic polymorphisms of apolipoprotein (apo) A‐IV have been shown to influence lipoprotein metabolism in some human populations. In this study, we have evaluated the physiological effect of three apo A‐IV polymorphisms (Gln360‐ < His, Thr347‐ < Ser and XbaI within the second intron of the apo A‐IV gene), in a French population, on seven quantitative traits: total cholesterol and triglycerides, cholesterol of HDL, apo A‐IV, apo B, apo A‐I and glucose. The polymorphism at amino‐acid 360 was determined by direct analysis of polymerase chain reaction products. The allele frequencies were 0.92 for the A‐IV1 and 0.08 for the A‐IV2 allele. The genetic polymorphism at codon 347 was investigated by allele‐specific oligonucleotide hybridization. The allele frequencies of the two alleles, A‐IV347Thr and A‐IV347Ser, were 0.78 and 0.22, respectively. The XbaI polymorphism was investigated by polymerase chain reaction followed by XbaI restriction enzyme digestion of the amplified products. The frequencies of the two apo A‐IV alleles, XbaI‐1 and XbaI‐2, were 0.79 and 0.21, respectively. None of the three apo A‐IV polymorphisms had a significant effect on lipoprotein, apolipoprotein and glucose levels.
A case of de novo interstitial deletion of chromosome 9(p12p13)
Authors: Giltay Jacques C. , Gerssen‐Schoorl Klasien B. J. , van der Wagen Ab
Published: July 2010

The present paper describes a girl with a small de novo deletion of chromosome 9(p12p13). This deletion has not been published previously. The deleted fragment is clearly outside the region involved in the so‐called deletion 9p syndrome. The patient had mild dysmorphic features and feeding problems during the first weeks of life, but is now developing well. Because of the lack of severe clinical features in this patient, we speculate that the deletion may be prevalent in other patients who have no clinical indication for chromosome investigation.
Association between genetic variation at the APO AI‐CIII‐AIV gene cluster and familial combined hyperlipidaemia
Authors: Xu Chun‐Fang , Talmud Philippa , Schuster Herbert , Houlston Richard , Miller George , Humphries Steve
Published: July 2010

By using chemical cleavage mismatch analysis and the single strand conformation polymorphism technique, DNA fragments of the apo CIII gene, including the 5′ flanking region and all the exons, were screened for sequence changes underlying the observed association between familial combined hyperlipidaemia (FCHL) and the apo AI‐CIII‐AIV gene cluster in affected individuals from eight FCHL families. A C1100‐T transition in the wobble position of codon 14 in exon 3 and a T3206‐G transversion in the non‐translated region of exon 4 were identified, occurring in four and all probands, respectively. Using these variants and the G_75‐A transition in the apo AI promoter, co‐segregation of the gene cluster with hyperlipidaemia could be excluded in all eight families (lod score ‐∞ at θ=0). No support for co‐segregation was obtained using the affected pedigree member method of linkage analysis (overall T=–0.77 for f (p)=1√p). The frequencies of T1100 and G3206 in a group of 55 patients with combined hyperlipidaemia were 0.35 and 0.52, respectively, which were significantly higher compared to 360 controls (0.21, p<0.01 and 0.35 p<0.005 respectively). In patients homozygous for the T1100 allele, levels of plasma triglyceride were 2.5‐fold higher (868 mg/dl) than those homozygous for the C1100 allele (337 mg/dl), while patients heterozygous for the polymorphism had intermediate values (443 mg/dl) (p<0.01). A similar association was seen in controls (p<0.04). The three polymorphisms studied were in strong linkage disequilibrium in both the group of CHL patients and the unrelated individuals. This study confirms the association between common variation in the gene cluster and differences in plasma lipid levels in the general population and in patients with combined hyperlipidaemia, but fails to confirm co‐segregation with FCHL, suggesting the role of other genetic or environmental factors in the aetiology of FCHL.
Changes in Lp(a) lipoprotein and other plasma proteins during acute myocardial infarction
Authors: Andreassen Arne K. , Berg Kåre , Torsvik Harald
Published: July 2010

The sequential changes of Lp(a) lipoprotein concentrations in patients (n=59) suffering acute myocardial infarction (AMI) were examined and compared with other plasma proteins. The temporal and quantitative characteristics of the responses in concentration of acute phase reactants (CRP, haptoglobin, α1‐antitrypsin, α‐acid glycoprotein), lipids (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol) and apolipoproteins AI and B were similar to previous reports. Lp(a) lipoprotein showed transient changes with an initial decrease of 10–25% compared to the 3‐month control value, followed by rebound on day 7–11 above admission level, before again declining. We were able to demonstrate a quantitative relationship between infarct size and alterations in plasma levels of acute phase reactants. However, in addition to rather unusual significant fluctuations during AMI, Lp(a) lipoprotein changes seemed unrelated to infarct size. These findings do not support the view that Lp(a) lipoprotein acts as an acute phase reactant.
Partial trisomy of the short arm of chromosome 18 due to inversion duplication and direct duplication
Authors: Moog U. , Engelen J. J. M. , de Die‐Smulders C. E. M. , Albrechts J. C. M. , Loneus W. H. , Haagen A. A. M. , Raven E. J. M. , Hamers A. J. H.
Published: July 2010

We report one patient with a de novo inversion duplication 18 (ptercen) and two cases of direct tandem duplication 18 (ptercen), one due to maternal inheritance and the other arising as mosaicism of unknown origin. The duplications are demonstrated by high resolution banding. They were verified by in situ hybridization with a paint specific for chromosome 18 and with DNA probe LI.84 specific for the centromere region of chromosome 18. FISH with the genomic DNA probe pHRR68 specific for 18p11.32 revealed a subtle deletion concomitantly involved in the case of inversion duplication 18p. The patients exhibit slight developmental delay/moderate mental retardation and only a few dysmorphic features. The literature on trisomy 18p is reviewed and the present cases are compared to it.
No effect of a BglI polymorphism at the renin (REN) locus on blood pressure level or variability
Authors: Berge K. E. , Berg K.
Published: July 2010

We have studied a normal restriction fragment length polymorphism at the renin locus, detected with the restriction enzyme BgII in healthy Norwegians. No association with blood pressure level or variability was found. Thus, the normal genes detected by examination of this restriction fragment length polymorphism at the renin locus have neither “level gene” nor “variability gene” effects on normal blood pressure.
Effect of the StuI polymorphism in the LDL receptor gene (Ala 370 to Thr) on lipid levels in healthy individuals
Authors: Gudnason V. , Patel D. , Sun X‐M. , Humphries S. , Soutar A.K. , Knight B.L.
Published: July 2010

We have examined the effect on plasma lipid levels of a single base change in exon 8 of the LDL receptor gene that causes an amino acid change Ala 370 to Thr in a sample of 318 Icelandic individuals selected at random from the general population. The change destroys a StuI restriction site and was detected by digestion of pooled samples in groups of 5. The frequency of the loss of the cutting site was 0.05 (95%CI=0.014‐0.054). In men, those with the Thr allele (n=18) had 8.3% higher total cholesterol, 11.8% higher LDL cholesterol and 10.3% higher apolipoprotein B than those with the common Ala allele, whereas in women those with the Thr allele (n=12) had levels lower by 7.4%, 13.3% and 10.1% respectively. These differences reached statistical significance only in the men (p<0.05). Functional analysis of CHO cells transfected with constructs of the LDL receptor cDNA carrying the Ala370 and Thr370 alleles showed that within the limits of the assays there was no difference in function of the LDL receptor protein as measured by uptake and degradation of LDL. The data raise the possibility that amino acid substitutions that could affect LDL receptor function below the limits of detection by conventional assays, may have an effect on plasma lipid levels in the general population.
Split foot and developmental retardation associated with a deletion of three microsatellite markers in 7q21.2‐q22.1
Authors: Marinoni Jean‐Christophe , Stevenson Roger E. , Evans James P. , Geshuri Dorrit , Phelan Mary C. , Schwartz Charles E.
Published: July 2010

A deletion of 7q21.2‐q22.1 has been found in a patient with split foot and developmental retardation. Molecular analysis using polymerase chain reaction (PCR) showed deletion of three microsatellite markers, D7S527, D7S479 and D7S554, in the patient's paternal chromosome. These results pinpoint the critical region for an ectrodactyly locus (SHFD1) on chromosome 7.
Association of HincII RFLP of low density lipoprotein receptor gene with obesity in essential hypertensives
Authors: Zee Robert Y. L. , Schrader Andrew P. , Robinson Bruce G. , Griffiths Lyn R. , Morris Brian J.
Published: July 2010

Obese (BMI 26 kg/m2; n=51) and lean (BMI <26 kg/m2; n=61) Caucasian patients with severe, familial essential hypertension, were compared with respect to genotype and allele frequencies of a HincII RFLP of the low density lipoprotein receptor gene (LDLR). A similar analysis was performed in obese (n=28) and lean (n=68) nonmotensives. A significant association of the C allele of the T → C variant responsible for this RFLP was seen with obesity (x2=4.6, P=0.029) in the hypertensive, but not in the normotensive, group (odds ratio=3.0 for the CC genotype and 2.7 for CT). Furthermore, BMI tracked with genotypes of this allele in the hypertensives (P=0.046). No significant genotypic relationship was apparent for plasma lipids. Significant linkage disequilibrium was, moreover, noted between the HincII RFLP and an ApaLI RFLP (x2=33, P<0.0005) that has previously shown even stronger association with obesity (odds ratio 19.6 for cases homozygous for the susceptibility allele and 15.2 for heterozygotes). The present study therefore adds to our previous evidence implicating LDLR as a locus for obesity in patients with essential hypertension.
Skipping of exon 12 as a consequence of a point mutation (1898 + 5G → T) in the cystic fibrosis transmembrane conductance regulator gene found in a consanguineous Chinese family
Authors: Zielenski Julian , Markiewicz Danuta , Lin Shuan‐Pei , Huang Fu‐Yuan , Yang‐Feng Teresa L. , Tsui Lap‐Chee
Published: July 2010

A point mutation (1898+5G→T) located five base pairs downstream from the donor splice site in intron 12 of the CFTR gene has been identified in a consanguineous CF patient of Chinese origin. To determine if this nucleotide substitution could affect mRNA splicing, PCR analysis was performed with RNA isolated from the lymphoblastoid cell line of the mother of the deceased patient. While exon 12‐minus transcript was detected in this sample, it was also found in individuals without 1898+5G→T, albeit in a smaller proportion. Using a sequence polymorphism associated with each of the two alleles in the mother, however, we showed that mutant transcript was almost exclusively produced by the 1898+5G→T allele. Skipping of exon 12 would result in the deletion of 29 amino acids from the first nucleotide binding domain of CFTR, rendering the protein non‐functional. The possibility of a low level (2.5%) of normal transcript from the mutant allele cannot be excluded and it may explain the pancreatic sufficient phenotype of the patient. The 1898+5G→T mutation was found in two other CF patients of Chinese origin, but it was not detected in 192 CF chromosomes of Caucasian origin and 30 other chromosomes from Chinese individuals without a family history of CF.
Skin color and cancer mortality among black men in the Charleston Heart Study
Authors: Knapp Rebecca G. , Keil Julian E. , Sutherland Susan E. , Rust Philip F. , Hames Curtis , Tyroler Herman A.
Published: July 2010

The association between skin color and 30‐year cancer mortality in a random sample of black men and a peer‐nominated group of high socioeconomic status (SES) black men was evaluated in the Charleston Heart Study, a prospective study, begun in 1960, designed to investigate the epidemiology of coronary heart disease in a biracial cohort. Skin color was used as a continuous variable and as a categorical variable, by tertiles, in a Cox proportional hazards regression model. In the high SES group, there was a statistically significant decreasing relationship between skin color and cancer mortality, with those having the lightest skin having the lowest cancer mortality. In the random sample of black men, the relationship between skin color and cancer mortality was not statistically significant; however, the data indicated a slight protective effect among those with the lightest skin color. Because degree of skin reflectance is a measure of black‐white admixture, these results may indicate a genetic mechanism underlying the differences in cancer mortality across skin color groups. Skin color is also recognized as a marker for psychosocial factors. Therefore, poor prognosis among those with darker skin color as a result of failure of early detection, inadequate treatment, and a variety of psychosocial stressors represents an alternative explanation of the study findings.
Symptomatic heterozygosity in the Ellis‐van Creveld syndrome?
Authors: Spranger Stephanie , Tariverdian Gholamali
Published: July 2010

A 13‐month‐old girl with Ellis‐van Creveld syndrome and her mildly affected father are described. We discuss whether the father is a symptomatic heterozygote of the Ellis‐van Creveld syndrome or an untypical affected patient with Weyers' acrodental dysostosis.
A case of Marden‐Walker syndrome with Dandy‐Walker malformation
Authors: Özkinay F. , Özyürek A. R. , Bakiler A. R. , Narin N. , Yüksel H. , Özkinay C. , Parlar A. , Arcasoy M.
Published: July 2010

A 5‐month‐old girl with Marden‐Walker syndrome is presented. This is a rare autosomal recessive syndrome. So far, approximately 20 cases have been described in the literature. The patient was hospitalized because of difficulty in feeding and slow spontaneous movements. Her parents were first cousins. She was diagnosed with clinical findings of growth and motor retardation, typical facial appearance, congenital heart disease, arachnodactyly, joint contractures, and a Dandy‐Walker malformation on magnetic resonance imaging.
Screening of neurofibromatosis type 1 gene: identification of a large deletion and of an intronic variant
Authors: Grifa Anna , Piemontese Maria Rosaria , Melchionda Salvatore , Origone Paola , Zelante Leopoldo , Coviello Domenico , Fratta Giovanni , Dallapiccola Bruno , Balestrazzi Paolo , Ajmar Franco , Gasparini Paolo
Published: July 2010

Neurofibromatosis type 1 of von Recklinghausen is a common autosomal dominant disorder, characterized by peripheral neurofibromas, café‐au‐lait spots and Lisch nodules of the iris. The high mutation rate at the neurofibromatosis type 1 locus results in a wide range of molecular abnormalities. We have screened seven different exons of the neurofibromatosis type 1 gene, including those codifying for the GAP‐related domain, using the RNA‐Single Strand Conformation Polymorphism (RNA‐SSCP) method in a series of 59 neurofibromatosis type 1 patients. We have also analyzed four intragenic repeats and one RFLP to detect hemizygosity and evaluate informativeness in at‐risk families. One deletion and a new intronic normal variant have been detected. Thus the majority of Neurofibromatosis type 1 chromosomes have not been characterized, confirming difficulty in providing proper genetic counselling in neurofibromatosis type 1 families, even following extensive DNA analysis.
Aplasia cutis congenita and associated disorders: an update
Authors: Evers Mirjam E. J. W. , Steijlen Peter M. , Hamel Ben C. J.
Published: July 2010

We present an update of disorders in which aplasia cutis congenita is a feature. Localization of the lesion, important other features, and possible etiology are tabulated. Disorders are classified as chromosomal, monogenic, teratological/exogenous, and unknown. Points of particular interest in history taking and examination of patients with aplasia cutis congenita are presented.
Detection of α‐thalassemia‐1 (Southeast Asian type) and its application for prenatal diagnosis
Authors: Winichagoon Pranee , Fucharoen Suthat , Kanokpongsakdi Sujin , Fukumaki Yazuyuki
Published: July 2010

A simple non‐radioactive method based on the polymerase chain reaction was used to detect the Southeast Asian type of α‐thalassemia 1 (–). Three oligonucleotide primers, one of which was adjacent to the breakpoint of the α‐thalassemia‐1 allele, were used to amplify the 570 and 194 bp DNA fragments. The 570 bp product was specific to the α‐thalassemia‐1 determinant and the 194 bp fragment was amplified from either the α‐thalassemia‐2 (‐α) or normal α‐globin (αα) determinants. In Hb Bart's hydrops fetalis (–/–), only the 570 bp fragment was obtained, whereas the 194 bp fragment was amplified in normal individual (αα/αα) and α‐thalassemia‐2 trait (‐α/αα). Both 570 and 194 bp fragments were detected in α‐thalassemia‐1 trait (–/αα) and Hb H patients (–/‐α). This procedure is useful for the rapid screening of α‐thalassemia‐1 trait and prenatal diagnosis of Hb Bart's hydrops fetalis in populations with a high frequency of the Southeast Asian Type of α‐thalassemia‐1.
Atypical methylmalonic aciduria with progressive encephalopathy, microcephaly and cataract in two siblings — a new recessive syndrome?
Authors: Strómme P. , Stokke O. , Jellum E. , Skjeldal O.K. , Baumgartner R.
Published: July 2010

Two siblings with atypical methylmalonic aciduria and progressive encephalopathy are reported. Initial symptoms were failure to thrive and growth retardation from the first year of life, progressing to severe mental retardation, microcephaly, dystonia, spasticity and cataracts. The amount of methylmalonic acid excreted in the urine was substantially lower than in classical methylmalonic acidemia and was not reduced by vitamin B12 therapy. The activity of methylmalonyl‐CoA mutase and the overall assay of propionic acid metabolism in cultured fibroblasts were normal. The primary defect in this probably new autosomal recessive disorder associated with methylmalonic aciduria is currently not known.
Health care utilization and perceptions of health among adolescents and adults with Turner syndrome
Authors: Cunniff Christopher , Hassed Susan J. , Hendon Amy E. , Rickert Vaughn I.
Published: July 2010

We surveyed women aged 12 years and older who are members of the Turner Syndrome Society of the United States in regard to their health history, current health status, and health care utilization practices to identify the range of health problems and health care practices in this group. The mean age at diagnosis was 10.8 years, and an endocrinologist (41%) or pediatrician (35%) was most likely to make the initial diagnosis. Individuals over age 35 years were diagnosed with Turner syndrome and begun on estrogen replacement therapy at a significantly older age than those who were in younger age groups. Seventy‐five percent of the respondents had required some type of surgical procedure, and 14% had been hospitalized within the previous year. Ninety‐four percent of women rated their overall health as good to excellent, while 6% rated it fair to poor. In the 12–17‐year age group, 89% of the young women were either currently taking or had previously taken growth hormone. The prevalence of major depressive symptoms was slightly higher than the general population for adolescents but similar to the general population for adults. For adult respondents, ratings of fair to poor health were significantly associated with increased outpatient visits. Growth hormone use was significantly associated with increased visits in the adolescent population. Based on these data, it appears that the clinical care of individuals with Turner syndrome has improved, but that they continue to have relatively high hospitalization rates and utilization of subspecialty services. Despite these health problems, most respondents demonstrated good adjustment as determined by standardized mental health measures.
Molecular characterization of trisomic segment 3p24.1→3pter: a case with review of the literature
Authors: Conte Robert A. , Pitter Jean H. , Verma Ram S.
Published: July 2010

A 1‐year‐old male infant was found to have a de novo unbalanced translocation, resulting in trisomy for a portion of the short arm of chromosome 3, i.e. 46,XY,der(7)t(3;7) (p24.1;p22). Previous cases with a so‐called “trisomy 3p syndrome” were evaluated by GTG banding, while we attempted to characterize the present case by the FISH‐technique. The major clinical features included: dysmorphic ears, decreased muscle tone and seizure episodes associated with fever, which are concordant with “trisomy 3p syndrome”. The most common malformations of trisomy 3p syndrome are: psychomotor and mental retardation, short neck, hypertelorism/telecanthus and congenital heart defects. Predominantly, the 3p trisomies have been maternally derived and the major mechanism of inheritance is due to a malsegregation of the chromosomes that are involved in a parental balanced translocation. A review of 44 cases from 35 studies revealed that the clinical manifestations have been quite varied, depending upon the amount of 3p2 material in the trisomic state, but interestingly a recognizable pattern of features was obvious in those cases whose cytogenetic findings and clinical histories were known.
Tracheoesophageal anomalies in oculoauriculovertebral (Goldenhar) spectrum
Authors: Sutphen Rebecca , Galan‐Gomez Enrique , Cortada Xavier , Newkirk Patricia N. , Kousseff Boris G.
Published: July 2010

Tracheoesophageal fistula, with or without esophageal atresia (TEF/EA) appears to be a defect of blastogenesis, as is the oculoauriculovertebral (Goldenhar) spectrum (OAVS), with which it has occasionally been associated. We reviewed the records of all OAVS patients evaluated through the University of South Florida Regional Genetics Program between 1985 and 1993. Of 60 OAVS patients, three had TEF/EA. These results suggest that TEF/EA in association with OAVS is underreported. The occurrence of TEF/EA should prompt a thorough search for other known anomalies of OAVS.
Noonan syndrome with café‐au‐lait spots and multiple lentigines syndrome are not linked to the neurofibromatosis type 1 locus
Authors: Ahlbom Bodil Edman , Dahl Niklas , Zetterqvist Per , Annerén Goran
Published: July 2010

Noonan syndrome, multiple lentigines syndrome (LEOPARD syndrome), Watson syndrome and neurofibromatosis type 1 share certain clinical manifestations. We present a linkage analysis using microsatellite markers located in the neurofibromatosis type 1 region at 17q11 in a family with Noonan syndrome and café‐au‐lait spots and in another family with multiple lentigines syndrome. No linkage of the disease to the neurofibromatosis type 1 locus was found in the families investigated. On the basis of our results, we suggest that neither familial multiple lentigines syndrome nor Noonan syndrome is caused by a defect in the neurofibromatosis type 1 gene.
Identification of the valine 408 to methionine mutation in the LDL receptor in a Greek patient with homozygous familial hypercholesterolemia
Authors: Schuster H. , Manke C. , Fischer J. , Keller C. , Wolfram G. , Zöllnery N.
Published: July 2010

We have identified the cytosine to thymine change in the codon for amino acid 408 which causes valine to be replaced by methionine in exon 9 of the LDL receptor gene in a 12‐year‐old Greek boy living in Germany, with homozygous familial hypercholesterolemia, by using polymerase chain reaction‐amplified genomic DNA and subsequent restriction digestion. Homozygosity was confirmed by direct DNA sequencing. The mutation was present in both his parents, and his brother, grandmother, uncle and cousin. Six restriction fragment length polymorphisms of the LDL receptor gene were used to determine the haplotype of the defective allele. The haplotype was different from the one reported earlier in African Afrikaners and from Holland. We conclude that the mutation in the Greek boy probably occurred as an independent mutation. Because the parents are from different areas in Greece, this mutation may be common in Greeks.