bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene‐gene interaction between the low density lipoprotein receptor and apolipoprotein E loci affects lipid levels
Authors: Chr Jan , Berg Kåre
Published: July 2010

A restriction fragment length polymorphism (RFLP) at the low density lipoprotein receptor (LDLR) locus, detectable with the restriction enzyme PvuII has been studied in a second series of Norwegian subjects, believed to be representative of the general population. The results confirm the association of normal alleles at the LDLR locus with differences in age‐ and sex‐corrected total and LDL cholesterol. A gene identified as one of the alleles in this RFLP appears to eliminate the effect of the apolipoprotein E4 (apoE4) gene on cholesterol (or its allele must be present for the apoE4 effect on lipid level to manifest itself). The findings in this series substantiate previous indications that normal alleles are of importance in the control of LDLR activity and that normal LDLR alleles contribute to the population variation in cholesterol. Finally, they confirm that an interaction between LDLR and apoE genes contributes to the population variation in total and LDL cholesterol.
The wrinkly skin syndrome: a report of a case and review of the literature
Authors: Hurvitz S. A. , Baumgarten A. , Goodman R. M.
Published: July 2010

A 2 1/2‐year‐old boy born of Jewish Moroccan parents is reported with physical findings of wrinkled skin on the dorsum of the hands and feet, with poor skin elasticity, syndactyly, mild kyphosis and poor muscle tone, the diagnosis being the wrinkly skin syndrome. All reported cases of this heritable disorder of connective tissue are reviewed and discussed in terms of genetics, ethnic clustering and differential diagnosis.
Amniotic fluid microvillar enzyme activity in fetal malformations
Authors: Szabó Mária , Veress Lajos , Teichmann Farkas , Münnich Åkos , Huszka Mariann , Papp Zoltán
Published: July 2010

Prenatal diagnosis of cystic fibrosis based on amniotic fluid microvillar enzyme activity assay has become routine practice in the past few years. Normal (median) values of these enzymes were determined in 177 normal healthy pregnancies between 15–20 gestational weeks and were related to enzyme values measured in 50 pregnancies complicated with congenital malformations, 6 monogenic inherited diseases and 4 chromosomal aberrations. It is concluded that increased trehalase activity has diagnostic importance in detecting fetal kidney diseases, and radial‐renal syndrome (with elevated GGT activity), while low enzyme activities may indicate chromosomal aberrations (with no signs of intestinal obstruction). With the collection of further data, the analysis of these enzymes might provide an opportunity to set up diagnostic procedures for the detection of other, non‐CF‐related cases.
A familial form of convulsive disorder with or without mental retardation limited to females: extension of a pedigree limits possible genetic mechanisms
Authors: Fabisiak Keith , Erickson Robert P.
Published: July 2010

An unusual pedigree of female‐limited seizures with or without mental retardation is updated. The disorder was first detected in a large cohort of women whose fathers were brothers, and affected women had previously transmitted the disorder. Four brothers of affected females have now had five unaffected daughters while four affected women have had four affected and one unaffected daughters and two unaffected sons. This unusual transmission pattern is discussed in terms of germ‐line imprinting, neuronal sexual differentiation, and the generally higher risk of seizures seen when the mother, rather than the father, is affected.
Three years' diagnostic experience with direct karyotyping of neonatal blood
Authors: Garnham I. , Sutherland G. R.
Published: July 2010

Three years' experience with direct karyotyping of cord blood and neonatal venous blood is recorded. Fifty cord blood samples have been processed and 39 yielded satisfactory diagnostic results. Eight of 14 neonatal venous blood samples yielded diagnostic chromosome results after direct karyotyping. Factors which affected success are discussed.
Deficiency of distal 8p —: report of two cases and review of the literature
Authors: Pecile V. , Petroni M. G. , Fertz M. C. , Filippi G.
Published: July 2010

A terminal deletion in the short arm of chromosome 8 was found in a 2.5‐year‐old boy: 46,XY,del(8) (p22.0) and in a 1‐year‐old girl: 46,XX,del(8) (p23.1) with dysmorphic craniofacial features and developmental retardation. Erythrocyte GSR activities of the boy and of his parents were within normal limits. Vitamin K dependent coagulation factors in the girl and her parents gave normal results. Clinical findings were compared with previously reported cases and suggested a recognizable syndrome.
Genetic studies of human apolipoproteins. XVI. APOE polymorphism and cholesterol levels in the Mayans of the Yucatan Peninsula, Mexico
Authors: Kamboh M. I. , Weiss K. M. , Ferrell R. E.
Published: July 2010

Structural variation at the APOE locus is a major determinant of interindividual differences in cholesterol levels in populations at large. We have determined APOE structural polymorphism and estimated its impact on total cholesterol in the Mayans of the Yucatan Peninsula from Mexico. A unique pattern of APOE allele frequency distribution was observed, with no example of the APOE*2 allele and a relatively low incidence (9%) of the APOE*4 allele, giving rise to the lowest average heterozygosity at the APOE locus observed to date. The reported elevating affect of the APOE*4 allele on cholesterol has been found to be absent in the Mayans; several possible explanations which may account for the absence of this affect are discussed. In addition to APOE the gene products of five other apolipoprotein loci were screened and low frequency variation, possibly due to European admixture, was observed in two systems (APOH and APOA‐IV).
Recurrent neuroleptic malignant syndrome associated with inv dup(15) and mental retardation
Authors: Lazarus Arthur L. , Moore Kenneth E. , Spinner Nancy B.
Published: July 2010

Neuroleptic malignant syndrome (NMS) is an uncommon but serious adverse reaction to neuroleptic drugs. Clinically, it resembles malignant hyperthermia, a pharmacogenetic disorder of anesthesiology. Inv dup(15) is a rare but underrecognized cause of mental retardation among institutionalized patients. NMS and inv dup(15) have not been previously reported together. Their association should encourage clinicians to search for genetic markers for NMS.
The prevalence of chromosome diseases in the general population of Sichuan, China
Authors: Zhang Sizhong , Xie Tao , Tang Yongcai , Zhang Silig , Xu Yin
Published: July 2010

Chromosome abnormalities with recognizable clinical manifestations including mental retardation, primary infertility or primary amenorrhea of unknown etiology, abnormal sex differentiation and abnormal sex development were surveyed in the general population of Sichuan. The results showed that the prevalence of chromosome diseases in Sichuan was 31.5 per 100000 of the general population with almost equal frequencies for autosomal chromosome and sex chromosome diseases. The most frequent autosomal chromosome disease was Down syndrome. The prevalence was 14.2 per 100000 for the total population, and there should therefore be 154 000 cases of Down syndrome in the whole of China with its population of 1100 million people. The most frequent sex chromosome diseases were Turner syndrome and Klinefelter syndrome. The prevalences were 14.3 and 14.1 per 100000 for females and males, respectively. The majority of autosomal chromosome diseases clustered in the younger age groups, while the highest detection rate of sex chromosome diseases was found in the age group of 25–35, and thereafter it decreased with age. The age distribution of the cases indicates that both autosomal and sex chromosome diseases reduce the lifespan of patients.
Robertsonian translocation and an extra microchromosome: independent origin identified by in situ hybridization
Authors: Heppell‐Parton A. C. , Waters J. J.
Published: July 2010

Robertsonian translocation may result in either a monocentric or a dicentric product involving the long arms of the participating chromosomes. In the former case a microchromosome involving the short arms of both acrocentrics would be expected to arise, but in practice is rarely observed. Where such small bisatellited markers are seen in association with Robertsonian translations, they are assumed to represent such reciprocal products. We present a case, involving a t(14q21q) and a DA/DAP1 positive microchromosome, where using in situ hybridization we show that this assumption is incorrect and that the microchromosome has arisen independently.
Counselling under genetic heterogeneity: a practical approach
Authors: Narod Steven
Published: July 2010

Hereditary diseases due to mutation at different gene loci may be indistinguishable phenotypically. In these situations genetic risk predictions using polymorphic markers may be hampered if an individual family is not sufficiently informative to permit it to be assigned to one or the other linkage group. To provide the most useful estimates of risk, the probability of linkage to a particular chromosome region should be determined prior to calculating risk estimates using the marker system. The probability can be calculated directly using the lod score generated for the family. The individual carrier risk is then the average of the carrier risks determined for linkage to different genetic loci, weighted by the probability of linkage to each group. Several examples are provided.
Ring chromosome 4 in a child with mild dysmorphic signs
Authors: Freyberger Gabriele , Wamsler Christine , Schmid Michael
Published: July 2010

We report on an 8‐year‐old boy exhibiting microcephaly, clinodactyly and growth retardation. Chromosome analysis showed a ring chromosome 4 in 97% of the cells and a high number of hyperploid cells with various ring formations. The breakpoints are presumed to be close to or in the telomeric regions of both arms. The patients reported with ring chromosome 4 and breakpoints close to the telomeres of both arms showed unspecific, mild clinical findings with normal or retarded mental development. These signs are probably related to the continuous generation of aneuploid cells.
Restriction fragment length polymorphism analysis of the C1‐inhibitor gene in hereditary C1‐inhibitor deficiency
Authors: McPhaden A. R. , Birnie G. D. , Whaley K.
Published: July 2010

Four out of 12 kindreds with Type I hereditary angio‐oedema (HAE) were shown to have unique disease‐related restriction fragment length polymorphism (RFLPs) in one allele of the C1‐inhibitor gene. These RFLPs were used to localise the gene mutations responsible for them in each family. The four mutations affected exon 4, exon 6, exon 7 and exon 8, respectively. Mutations in exon 6 and exon 8 have not been described previously in Type I HAE. The other two mutations which comprised an exon 4 deletion and an exon 7 deletion have already been documented by other investigators. In each family the mutation was seen to cosegregate with the disease. Detection of a disease‐related RFLP in 30% of the Type I HAE kindred tested is higher than other published studies, and reflects the larger number of restriction enzymes employed. These results suggest that Type I HAE is likely to be associated with a multiplicity of gene mutations as is seen in other genetic diseases. A new C1‐inhibitor gene‐related RFLP in the normal population was also characterised. This may be useful as an indirect marker of the mutant C1‐inhibitor allele in certain families with Type I HAE.
Dominantly inherited microcephaly, hypotelorism and normal intelligence
Authors: Evans D. G. R.
Published: July 2010

A family with dominantly inherited microcephaly, hypotelorism and normal intelligence is described. Their facial appearance is very similar, with malar hypoplasia. Psychometric testing in two generations revealed normal intelligence. Cranial CT scans showed no evidence of abnormality. This reports emphasises the need for family and psychometric studies in uncomplicated microcephaly.
Germ‐line mosaicism in Waardenburg syndrome
Authors: Kapur Saroj , Karam Susan
Published: July 2010

A family with three children with Waardenburg syndrome born to normal, unrelated parents is reported. This appears to be the first report suggesting germ‐line mosaicism in Waardenburg syndrome.
Hereditary hemorrhagic telangiectasia: report of 15 affected cases in a Mexican family
Authors: Guillén Bolívar , Guízar Jesús , de la Cruz José , Salamanca Fabio
Published: July 2010

We report a Mexican family with 15 members affected with hereditary hemorrhagic telangiectasia (HHT), all of them suffering from severe hemorrhagic episodes treated with multiple blood transfusions; one patient had a cerebral arteriovenous fistula that required surgical treatment and two others had severe cirrhosis of the liver. Clinical findings in this family illustrate the variable expressivity in HHT, which should be taken into account for the purpose of genetic counselling and monitoring for early detection of systemic complications.
Hypertrophic cardiomyopathy in late‐onset variant of Fabry disease with high residual activity of α‐galactosidase A
Authors: Nagao Yoshiro , Nakashima Haruko , Fukuhara Yukiko , Shimmoto Michie , Oshima Akihiro , Ikari Yuji , Mori Yoshio , Sakuraba Hitoshi , Suzuki Yoshiyuki
Published: July 2010

A new variant form of Fabry disease with hypertrophic cardiomyopathy of late onset is reported. Two unrelated male hemizygotes of this disease first presented with signs and symptoms of cardiomyopathy after 50 years of age. Cultured lymphoblastoid cells showed significantly higher residual αgalactosidase A activities than in the patients with classical phenotypic expressions.
A new family with chorioretinal dystrophy, spinocerebellar ataxia and hypogonadotropic hypogonadism (Boucher‐Neuhäuser syndrome)
Authors: Baroncini Anna , Franco Nicola , Forabosco Antonino
Published: July 2010

A family is described in which two brothers have spinocerebellar ataxia, hypogonadotropic hypogonadism and chorioretinal dystrophy. This report provides further evidence to support the previous suggestion that this triad of manifestations represents a specific single‐gene disorder, designated Boucher‐Neuhäuser syndrome. Analysis of affected individuals shows that neurological signs usually develop during adolescence or young adulthood (range: early childhood‐fourth decade) and are slowly progressive or non‐progressive, whereas ophthalmologic manifestations have an age of onset which varies from the first to the sixth decade of life and a pronounced variability in progression.
Familial short rib syndrome, type Beemer, with pyloric stenosis and short intestine, one case diagnosed prenatally
Authors: Balci Sevim , Erçal M. Derya , Önol Behsan , Çağlar Melda , Doğan Ahmet , Doğruel Nesrin
Published: July 2010

Two sibs with Beemer type short rib syndrome, one of them diagnosed in utero, are reported. Both patients had previously unreported additional abnormalities such as pyloric stenosis and short bowels. Dysplasia of pancreatic Langerhans cells was present in one sib.
Tuberous sclerosis in two sibs of normal parents
Authors: Rott H.‐D. , Fahsold R.
Published: July 2010

We report on a family with two sibs suffering from tuberous sclerosis. The parents were normal in all clinical tests including Wood's light examination of the skin, ophthalmoscopy, X‐ray computerized tomography of brain, liver, and kidneys, cardiac echography and MR imaging of the brain. The most likely explanation is a germinal cell mosaic in one of the parents. A recurrence risk of 20 to 37% seems appropriate. The implications for risk assessment of sporadic cases are emphasized.
Monozygotic twin girls with diploid/triploid chromosome mosaicism and cutaneous pigmentary dysplasia
Authors: Wulfsberg Eric A. , Wassel William C. , Polo Cynthia A.
Published: July 2010

Diploid/triploid mosaicism is an uncommon clinical syndrome with a subtle but distinctive phenotype. Characteristic features include prenatal and postnatal asymmetric growth deficiency, triangular and/or asymmetric facies, micrognathia, finger and/or toe syndactyly, clinodactyly, single transverse palmar creases, male genital anomalies, hypotonia and psychomotor retardation. This disorder is underdiagnosed because in 70% of cases the triploid cell line is only seen in fibroblasts. In cases in which a triploid cell line is found in lymphocytes, it usually occurs in less than 5% of cells. While some reports of diploid/triploid mosaicism have mentioned unusual skin pigmentary patterns, including hypomelanosis of Ito, it was only recently recognized that this is a helpful diagnostic clue in mosaic chromosome disorders. We report monozygotic twin girls with diploid/triploid mosaicism whose cutaneous pigmentary dysplasia led to their diagnosis.
Association of annular pancreas and duodenal obstruction – evidence for Mendelian inheritance?
Authors: Hendricks Susan K. , Sybert Virginia P.
Published: July 2010

This report presents a family with two individuals in two successive generations who were affected by annular pancreas and high duodenal obstruction. An argument for autosomal dominant transmission and implications for appropriate team management are discussed.
Hypothesis: association of the critical region of trisomy 18 and 18q2—syndrome with dermatoglyphic findings and a growth suppressor (deleted in colon cancer) locus
Authors: Reed Terry
Published: July 2010

Evidence from the literature is reviewed to suggest that when fingertip dermal ridge patterns in chromosomal deletion syndromes are characteristic of the opposite spectrum of the developmental scale from patterns found in cases trisomic for the same chromosomal region, the association may be a consequence of loci with growth regulatory functions. Evidence is presented that DNA markers at 18q21 should be the first candidate sequences to be used to test this hypothesis in families with fingertip arches segregating in an apparent autosomal dominant fashion.
Gene deletions in Japanese patients with Duchenne and Becker muscular dystrophies: deletion study and carrier detection
Authors: Asano Jun‐Ichi , Tomatsu Shunji , Sukegawa Kazuko , Ikedo Yuko , Minami Ryoji , Iida Mitsuo , Nishimura Masaaki , Nakagawa Masanori , Ohshiro Morio , Orii Tadao
Published: July 2010

Fifty unrelated Japanese patients with Duchenne and Becker muscular dystrophy (DMD and BMD) have been studied through use of the dystrophin cDNA probes. The 14‐kb dystrophin cDNA was subdivided into six subclones, and Hind III‐digested DNAs were analyzed by Southern blotting. Of 50 unrelated patients, 20 showed a deletion of one or several of the exon‐containing Hind III fragments (40.0%). These corresponded to 50% (11/22) of BMD patients and 32.1% (9/28) of DMD patients, and the position and extent of deletions were mapped and proven to be more heterogeneous in DMD than in BMD. Both ends of deletions detected by probe 1–2a were common to all six BMD patients, and the 5'ends of deletions in probe 5b‐7 were also common to four BMD patients. The phenotypic‐specific deletion in Japanese BMD patients existed in the 5'end of the DMD gene, although an apparently similar deletion produced a wide range of clinical courses (BMD phenotype). Three out of eight females in DMD/BMD families were diagnosed as carriers through use of the junctional fragment and dosage analyses of dystrophin cDNA.
Estimates of heritability of plasma homocyst(e)ine levels in aging adult male twins
Authors: Reed Terry , Malinow M. Rene , Christian Joe C. , Upson Barbara
Published: July 2010

Plasma homocyst(e)ine level was determined for 96 identical (MZ) and 92 fraternal (DZ) adult male twins aged 59–69. There was no difference in mean between MZ (10.31 nmol/ml) and DZ (10.36 nmol/ml) twins. The intraclass correlation coefficient of the log‐transformed homocyst(e)ine level in 43 complete MZ and 39 complete DZ pairs was 0.55 and 0.19, respectively. The MZ correlation was significantly (p<0.05) greater than the DZ correlation, suggesting that the level of plasma homocyst(e)ine is genetically influenced.
An apparently new mental retardation syndrome in three elderly sisters
Authors: Viljoen Denis L. , Kallis Jennifer , Voges Stella , Marais Anna‐Susan , van Vuuren Irene
Published: July 2010

Three elderly sisters with profound mental retardation in association with the clinical features of microcephaly, short stature, brachydactyly type D, flattened occiput, down‐slanting palpebral fissures, low‐set large ears, broad prominent nose and kyphoscoliosis have been investigated. Each was more than 60 years of age and their clinical features were strikingly similar. The disorder has several manifestations in common with Rubenstein‐Taybi syndrome and appears to be inherited as an autosomal recessive in this family.
Clinical investigation of females with the Martin‐Bell syndrome and risk assessment for carrier status
Authors: Thake A. , Webb T. , Marshall T.
Published: July 2010

Anthropometric measurements were made on a series of females heterozygous for the fragile‐X syndrome. It was found that there were no simple series of discriminating features separating those of normal IQ from the mentally handicapped, but rather that the carriers studied represented a wide spectrum of phenotype. When measurements performed on 15 FRAXA negative, obligate carriers of normal IQ were considered separately, it was found that there were certain common phenotypic features allowing risk figures to be amended for those females at 50% risk of being a carrier but who are also FRAXA negative.
Absence of predictable phenotypic expression in proximal 15q duplications
Authors: Ludowese Carol J. , Thompson Kate J. , Sekhon Gurbax S. , Pauli Richard M.
Published: July 2010

We describe ten individuals with an insertional duplication 15q12→q13. Phenotypic analysis of these individuals and 15 previously reported cases of proximal 15q duplications fails to show any consistent clinical manifestations. It appears that a duplication of this region is phenotypically silent.
Patients with deletions of 9q22q34 do not define a syndrome: three case reports and a literature review
Authors: Farrell S. A. , Siegel‐Bartelt J. , Teshima I.
Published: July 2010

Three children with deletions involving the 9q22q34 region are described. A review of clinical features of these three new patients and seven previously reported ones did not demonstrate a recognizable dysmorphic pattern. Our cases illustrate the need for repeat karyotyping at higher levels of resolution when there is a suspicion of a chromosome anomaly, since each deletion was missed on initial analysis.
Poland‐Moebius syndrome in a boy and Poland syndrome in his mother
Authors: Rojas‐Martínez A. , García‐Cruz D. , García A. Rodríguez , Sánchez‐Corona J. , Rivas F.
Published: July 2010

A 4 4/12‐year‐old boy with the Poland‐Moebius syndrome, whose mother had the Poland syndrome, is presented. This is the first report of the occurrence of both syndromes in the same family, suggesting that they are expressions of the same autosomal dominant gene.
Ectrodactyly‐ectodermal dysplasiaclefting syndrome (EEC): the clinical variation and prenatal diagnosis
Authors: Annerén G. , Andersson T. , Lindgren P. G. , Kjartansson S.
Published: July 2010

Six patients with the ectrodactyly‐ectodermal dysplasia‐clefting (EEC) syndrome, namely five members of the same family and one sporadic case, are presented. One of the main features of the EEC syndrome, ectrodactyly, was missing in five of the patients. The diagnosis did not become clear until the youngest son of the family was born. All of our six patients had a low birth weight and some were born preterm, and four had poly‐ and/or syndactyly without ectrodactyly. A low birth weight and polysyndactyly have been reported previously in patients with the EEC syndrome and might be features of the syndrome. The present patients illustrate the great phenotypic variability in the EEC syndrome and the need for a careful search for microsymptoms in potential gene‐carriers. In two members of the affected family, EEC syndrome was diagnosed prenatally after 16 weeks of gestation by detection of the cleft lip and palate on ultrasound examination. The mother chose to continue the pregnancies. However, prenatal diagnosis of cleft lip and palate might be of value in genetic counselling for other inherited syndromes leading to severe disability.
Tuberous sclerosis in a child with de novo translocation t(3; 12) (p26.3; q23.3)
Authors: Fahsold R. , Rott H.‐D. , Claussen U. , Schmalenberger B.
Published: July 2010

We report on an 8‐year‐old boy with severe mental retardation, epileptic seizures, autistic behaviour, and X‐ray CT findings of the skull characteristic for tuberous sclerosis. At the age of 9 years, first signs of adenoma sebaceum developed. Chromosomal analysis revealed a translocation t(3; 12) (p26.3;q23.3). The parents were both healthy and had normal karyotypes. As non‐random association of a chromosomal abnormality and tuberous sclerosis is hypothesized, a third locus for this disorder on 3p26 or 12q23 has to be taken in account.
X‐linked mental retardation with bilateral clasped thumbs: report of another affected family
Authors: Straussberg R. , Blatt I. , Brand N. , Kessler D. , Katznelson M. Bat‐Miriam , Goodman The Late R. M.
Published: July 2010

A Sephardi Jewish family is reported in which the two brothers had mental retardation, lower limb spasticity and bilateral clasped thumbs anomaly. This X‐linked recessive disorder has only been reported twice. We believe this syndrome comprises a distinct entity among the X‐linked mental retardation syndromes.
Endocrine and exocrine pancreatic function and the ΔF508 mutation in cystic fibrosis
Authors: Lanng Susanne , Schwartz Marianne , Thorsteinsson Birger , Koch Christian
Published: July 2010

The relationship between the cystic fibrosis (CF) genotype and endocrine and exocrine pancreatic function was studied in 215 CF patients. In the 211 patients with the ΔF508 mutation, endocrine pancreatic function (oral glucose tolerance; WHO criteria) was normal in 72.5%, impaired in 12.3%, and diabetic in 15.2% of the patients, with no difference between CF patients homozygous (N=163, median age 15 years, range 2–40) or heterozygous (N=48, 18 years, 3–40; age difference not significant) for the ΔF508 mutation. Exocrine pancreatic sufficiency (no need for pancreatic enzyme substitution) was found in 0.6% of the patients homozygous for the ΔF508 mutation and in 10.4% of the heterozygotes (p<0.01). Homozygous patients with pancreatic insufficiency took more pancreatic enzyme capsules (median 42 per day, range 0–192) than the heterozygotes (29 per day, 0–300; p<0.001). The four patients (1.9%) without the ΔF508 mutation had normal glucose tolerance but exocrine pancreatic insufficiency. In conclusion, the major mutation genotype in CF (ΔF508) affects the severity of the exocrine pancreatic insufficiency, whereas endocrine pancreatic function is unrelated to this genotype.
Mosaic tetraploidy in a liveborn infant with features of the DiGeorge anomaly
Authors: Wullich B. , Henn W. , Groterath E. , Ermis A. , Fuchs S. , Zankl M.
Published: July 2010

We report on a liveborn male infant with mosaic tetraploidy who presented with multiple congenital anomalies including features of the DiGeorge anomaly (type I truncus arteriosus with other cardiovascular malformations, thymic hypoplasia, hypocalcemia). No structural chromosome aberrations, namely of chromosome 22, were detected. These findings contribute to the variability of symptoms of the polyploid phenotype. Additionally, the cytogenetic studies in our case emphasize the necessity of investigating fibroblasts in order to evaluate the relevant proportion of aberrant cells in mosaicism.
Simultaneous expression of the rare and common fragile sites on the X chromosome
Authors: Zaslav Ann‐Leslie , Brown W. Ted
Published: July 2010

The fragile X [fra(X)] syndrome is the most common inherited form of X‐linked mental retardation and is associated with a rare folate sensitive fragile site on the X chromosome at band Xq27.3. Recently, a common fragile site located at chromosome band Xq27.2 was delineated (Sutherland & Baker 1990). In order to confirm the previous findings and to further investigate the conditions required for induction of both types of fragile sites, we studied the use of four experimental protocols. Samples from a control male, two fra(X) males and a fra(X) carrier female were studied. Both common and rare fragile sites were seen in the samples from the fra(X) subjects. Up to 4% of cells showed both common and rare fragile sites on the same X chromosome at the 500 band level. The rare and common fragile sites on the X chromosome could be clearly distinguished. From 1 to 3% of the control cells exhibited the common fragile site, while none exhibited the rare fragile site. These protocols should be useful in resolving questionable fra(X) syndrome diagnoses.
Strengths and weaknesses in the cognitive profile of youngsters with Prader‐Willi syndrome
Authors: Curfs L. M. G. , Wiegers A. M. , Sommers J. R. M. , Borghgraef M. , Fryns J. P.
Published: July 2010

In this report we present the results of a study of the intellectual functioning and cognitive profile of 26 Prader‐Willi syndrome (PWS) patients. The mean IQ score was 62.3 (range 39–96). In 13 patients a significant difference between verbal and performance IQ was found. In 10 of them the performance IQ was higher than the verbal. The results of subtest analysis indicate that cognitive strengths are more visible than cognitive weaknesses. Highest scores were noted especially in the performance scale, i.e. Block Design (9 children) and Coding or Mazes (5 children). Analysis of all available data indicates that PWS patients score better on visual motor discrimination skills than on auditory verbal processing skills. These results are promising for intervention programs and education stiategies.
Tests of performance of four semiautomatic metaphase‐finding and karyotyping systems
Authors: Korthof Gert , Carothers Andrew D.
Published: July 2010

Four commercially‐available semi‐automatic cytogenetic systems (Cytoscan, Ibas, Magiscan and Miamed) have been evaluated for both metaphase‐finding and karyotyping performances, using a common set of test slides and uniform criteria. Comparisons have been made in respect of timings, number and nature of operator interactions, and false positive and negative rates. Amongst the general conclusions are the importance, for metaphase‐finding performance, of a facility for ranking candidate metaphases according to their ‘analysability’, the need for some systems to reduce the time taken to relocate candidate metaphases, and the ability of all systems tested to detect analysable metaphases that were initially overlooked by a skilled cytogeneticist. In spite of automation, karyotyping remains a highly interactive process, strongly dependent on the skill and judgment of the operator, and therefore difficult to evaluate fully objectively.
A fragile X family with high penetrance in females: risk heterogeneity?
Authors: Martínez Francisco , Badía Lourdes , Prieto Félix
Published: July 2010

A fragile X family is described which shows two interesting features. In a sibship of seven, the two males and four of the five females are affected with mental retardation. Since the only normal daughter is not a carrier, the penetrance of the fragile X mutation in carrier daughters is 100%. Nevertheless, the penetrance of this syndrome in affected daughters of normal mothers has been estimated at a third. Also, DNA typing analysis of flanking RFLP markers revealed a higher than expected number of crossing‐overs. We also include the molecular study of the mutation in the (CGG)n repeat of the FMR‐1 gene.
Time of pubertal onset, testosterone levels and intelligence in 47,XXY males
Authors: Netley C.
Published: July 2010

This study examined the relations between verbal and performance IQs, time of pubertal onset and testosterone levels from 13 to 16 years of age in a sample of 30 males with a supernumerary X chromosome. The findings indicated that verbal IQs measured prior to puberty, during puberty and at mid‐adolescence were strongly related to relatively early pubertal onset and testosterone levels. Performance IQs had little or no relationship with the same variables. The results are discussed in terms of several different psychobiological models.
Association of haptoglobin types with serum lipids and apolipoproteins in a Chinese population
Authors: Saha N. , Liu Y. , Tay J. S. H. , Basair J. , Ho C. H.
Published: July 2010

Association of haptoglobin types with serum lipids and apolipoprotein levels was investigated in a healthy Chinese population of both sexes (n= 679) in Singapore. The frequency of Hp1 and Hp2 was found to be 0.30 and 0.70, respectively. The distribution of haptoglobin phenotypes was at Hardy‐Weinberg equilibrium in this population. There was an excess of Hp2 in individuals with the upper two quartiles of serum total cholesterol levels compared to those with the lower two quartiles in both sexes (X12: 11.84; P < 0.001). Subjects with Hp 2–2 had significantly higher serum total and LDL cholesterol levels (243.8 ± 2.83 and 165.9 ± 2.48 mg/dl) compared to those in other haptoglobin types (230.7 ± 2.58 and 154.9 ± 2.49 mg/dl), respectively (P < 0.001 and 0.002) after adjustments for age, sex and BMI. No other lipid (HDL cholesterol and triglyceride) and apolipoprotein (apo A‐I, A‐II and B) traits were associated with haptoglobin types. ANOVA statistics using age, sex and BMI as covariates showed that 1.8% of total variability of serum total cholesterol and 2.1% of serum LDL cholesterol could be explained by haptoglobin types (P 0.008 and 0.003, respectively). It is concluded that haptoglobin polymorphism is significantly associated with serum total and LDL cholesterol levels in this Chinese population.
X‐linked lymphoproliferative disease: prenatal detection of an unaffected histocompatible male
Authors: Mulley J. C. , Turner A. M. , Gedeon A. K. , Berdoukas V. A. , Huang T. H. M. , Ledbetter D. H. , Grierson H. , Purtilo D. T.
Published: July 2010

Chorionic Villous Biopsy (CVS) for diagnosis of XLP was undertaken at 10 weeks gestation in an obligate carrier. The fetus was found to be male by cytogenetic analysis. XLP (Xq25–q26) is closely linked to the RFLP markers DXS10, DXS37 and DXS42, but only DXS10 (distal to XLP) was informative for prenatal diagnosis in this family. RFLP analysis using this marker gave a 7% risk that the fetus was affected, based on the known recombination frequency between DXS10 and XLP. Further investigation was then undertaken to obtain a rapid and more accurate diagnosis using the three highly polymorphic PCR based markers. These were the AC repeat markers DXS424 (XL5A) and DXS425 (XL90A3) and the tetramer repeat marker within HPRT. DX425 is approximately 10 cM proximal to DXS10 and HPRT but is not known with certainty to map proximal or distal to XLP. DXS424 is proximal to DXS10 and HPRT and was inferred to be proximal to XLP on the basis of map distance from HPRT estimated by linkage analysis of data from CEPH pedigrees. This was confirmed by a recombinant in the XLP family between DXS424 and DXS425, placing DXS424 proximal to XLP. Diagnosis by linkage using DXS424 and DXS425, at least one of which is proximal to XLP, and distal markers DXS10 and HPRT, increased the accuracy of diagnosis using flanking marker analysis to greater than 99% that the fetus was unaffected. HLA DR typing of the CVS showed that the fetus was DR identical to a male sibling with XLP. HLA compatibility was confirmed at delivery by full HLA typing and MLC. Transplantation has been carried out utilising cord and placental blood.
Putative monosomy 21 in two patients: clinical findings and investigation using fluorescence in situ hybridization
Authors: Viljoen Denis L. , Speleman Frank , Smart Ronald , Roy Nadine Van , du Toit Joan , Leroy Jules
Published: July 2010

Complete monosomy 21 is claimed to be a rare chromosomal disorder in which the cytogenetic investigation is bedevilled by technical difficulties. We describe the disparate clinical features in two patients in whom an initial diagnosis of monosomy 21 was made by routine karyotyping. Fluorescence in situ hybridisation (FISH) confirmed a translocation of chromosome 21 material to the short arm of chromosome 5 and to the X chromosome, respectively. The usefulness of FISH in the investigation of subtle chromosomal rearrangements is hereby demonstrated. These findings also cast doubt on the existence of “pure” monosomy 21 as an entity, and suggest that partial monosomy 21 is a more likely occurrence.
X chromosome inactivation patterns in haematopoietic cells of female carriers of X‐linked severe combined immunodeficiency determined by methylation analysis at the hypervariable DXS255 locus
Authors: Hendrlks R. W. , Kraakman M. E. M. , Schuurman R. K. B.
Published: July 2010

The patterns of X chromosome inactivation were determined in 14 females from three unrelated X‐linked severe combined immunodeficiency (XSCID) pedigrees. All the females were found to be heterozygous for the hypervariable DXS255 locus, enabling analysis of differential methylation of this locus in peripheral blood haematopoietic cells. All six obligate carriers manifested a unilateral X chromosome inactivation in the T lymphocyte population. Differential methylation analysis of T lymphocytes was subsequently applied to establish the carrier status of females at risk in the XSCID pedigrees. In the B lymphocyte population of four XSCID carriers a unilateral X chromosome inactivation was observed. Four other carriers had minor fractions and one carrier had a substantial fraction of B lymphocytes with the XSCID gene defect on the active X chromosome. Within single XSCID pedigrees the carriers manifested different patterns. In two pedigrees the granulocyte populations of all carriers showed a random distribution of X chromosome inactivation. In the third pedigree the granulocytes of the three carriers analyzed manifested complete inactivation of the X chromosome that carried the XSCID mutation, exposing a selective disadvantage of granulocytes that express the XSCID defect. The pedigree‐dependent differences in the involvement of the granulocyte population suggest the existence of two distinct XSCID defects.
DNA probe technology: implications for service planning in Britain
Authors: Rona R. J. , Swan A. V. , Beech R. , Wilson D. M. , Kavanagh F. B. , Brown C. , Axtell C. , Mandalia S.
Published: July 2010

For certain genetic conditions DNA testing identifies carriers and determines the risk status of foetuses, thus helping parents to make more informed prenatal decisions. Data, collected from three genetic centres in England and Wales from August 1986 to July 1990, are used to describe trends in demand for DNA testing, the impact of DNA tests on carrier risk assessment, and the use of DNA tests in relation to pregnancy outcome. Altogether the data include 23 388 subjects and 681 pregnancies in 8738 families divided into five cohorts by year of entry and referral. The most frequent gene disorders referred to the genetic centres are currently being tested or will soon be tested. For these disorders the initial high level of activity has declined and may have reached steady state. Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis. Based on these findings we suggest that demand for DNA tests will be high in serious, untreatable and slow progressing conditions with early onset; intermediate for conditions affecting intellect and neurological integrity with later onset; and low for treatable, late‐onset conditions, or those for which there is evidence of heterogeneity, and variable penetrance. It would be helpful to assess the extent to which this view of demand is confirmed when the new disorders being DNA tested are considered and for the pattern of activity of DNA testing for some types of cancer. Since no DNA centre could offer a fully comprehensive testing service, it is recommended that a structure is created to audit overall activity, assist in policy formulation, and influence supraregional service organisation, in order that the spread of DNA services be planned as effectively as possible. This structure would facilitate monitoring of the evolution of contract specifications agreed by commissioners and providers on a regional basis.
Nucleotide sequence and PCR‐amplification of a polymorphic Mbol site in human DNA marker D4S95 linked to the Huntington disease locus
Authors: Nørremølle Anne , Sørensen Sven Asger , Arctander Peter
Published: July 2010

The nucleotide sequence of the probe BS674E‐D defining the genetic locus D4S95 was assessed, and used for designing PCR‐primers amplifying a 175 bp fragment containing a polymorphic Mbol site. With the described conditions it is now possible to use PCR followed by digestion for rapid determination of genotype in this marker system.
StyI polymorphism in an enhancer region of the second intron of the apolipoprotein B gene in hyper‐ and hypocholesterolemic subjects
Authors: Røshy Oddveig , Poledne Rudolf , Hjermann Ingvar , Tonstad Serena , Berg Kåre , Leren Trond P.
Published: July 2010

The regulation of the human apolipoprotein (apo) B gene that plays a crucial role in lipid metabolism is apparently very complex, with multiple cis‐ and trans‐acting regulatory factors. One of these factors is an enhancer region in the second intron. In this region a point mutation at position + 722 has been found that is detectable by the restriction enzyme StyI. The report of Levy‐Wilson et al. (1991) could suggest that the mutant allele (abolished StyI site) is associated with hypocholesterolemia. To investigate further the possible effect of this mutation on plasma cholesterol levels, we have compared the frequency of the mutant allele between 206 hypercholesterolemic Norwegian or Czech subjects on one hand, and 165 hypocholesterolemic Norwegian or Czech subjects on the other hand. No significant difference in frequency was found between the hypercholesterolemic and the hypocholesterolemic groups. This finding indicates either that the mutation at position + 722 does not affect the enhancer activity or that this in vitro enhancer activity is of little or no clinical significance. One of the Norwegian hypercholesterolemic subjects who was of Czech descent possessed the apoB 3500 mutation that leads to defective binding of low density lipoprotein (LDL) to the LDL receptors. Haplotype analysis of the apoB gene in her family showed that the mutation‐bearing allele was identical to that reported in other countries, indicating a common gene source.
β‐Thalassaemia mutations and their linkage to β‐haplotypes in Tamil Nadu in Southern India
Authors: Venkatesan Radha , Sarkar Rita , Old John M.
Published: July 2010

A study for screening of β‐thalassaemia mutations by the Amplification Refractory Mutation System (ARMS) and haplotyping by Polymerase Chain Reaction (PCR) was undertaken because there was a paucity of data in Tamil Nadu in Southern India and to initiate a comprehensive prenatal diagnosis programme. A total of 294 alleles were analysed to study the nature of the mutations, of which 146 were β‐thalassaemia alleles. Only four types of β‐thalassaemia mutations were recorded. Of these, 128 alleles were of the variant IVS‐1 nt 5 (G→C). Thirteen had the mutation codon 41/42 (del TCTT), four had the mutation codon 8/9 (insert G) and one had the 619 bp deletion at the 3′ end of the gene. The most common mutation, IVS–1 nt 5 (G→C), was strongly associated with a single haplotype although the association was not absolute. The population of Tamil Nadu in Southern India seems to be ideal for initiating a prenatal diagnosis programme based on direct detection of mutation by ARMS coupled with RFLP linkage analysis.
Deciphering the fluorescent variability of human genomic heterochromatin by DA/DAPI technique
Authors: Verma Ram S. , Conte Robert A. , Luke Sunay , Sindwani Veena , Macera Michael J.
Published: July 2010

A number of selective staining techniques have been utilized to decipher the variability of pericentromeric heterochromatin. One such technique is called DA/DAPI and it is believed to be stain specific. However, we demonstrate otherwise and suggest that pericentromeric regions of all human chromosomes stain positive by DA/DAPI‐technique. It must be emphasized that the incidence of DA/DAPI positive stained chromosomes, other than 1, 9, 15, 16 and Y, is a rare occurrence and only a small portion of the pericentromeric region is DA/DAPI positive, as reported here using 50 normal individuals.
Intrachromosomal insertion of chromosome 7
Authors: Farrell Sandra A. , Chow Grace
Published: July 2010

A direct intrachromosome insertion of chromosome 7 is described, and previous reports of intrachromosomal insertions are listed. All others were ascertained through a phenotypically abnormal proband. Ours is the first presenting with multiple pregnancy losses. Since the risk of chromo‐somally abnormal liveborns is appreciable, prenatal diagnosis should be made available to known carriers of chromosome insertions.
Differentiated recurrence risk estimations in the Prader‐Willi syndrome
Authors: Kennerknecht Ingo
Published: July 2010

The Prader‐Willi syndrome usually occurs sporadically. About 60% of the patients show a chromosomal deletion of proximal 15q. There are only a few reports on familial recurrence. Two previous estimates give either a low but recognizable recurrence risk of 1.6% or a risk of less than 0.1%. The inconsistency is obviously due to differences in the stringency of the diagnostic criteria used and to different modes of ascertainment of cases. This gave rise to a review of the literature, leading to the following suggestions: (1) A deletion at 15q has not been found in a familial case of PWS, except in those cases where del(15q) is due to familial structural chromosome rearrangements. Hence, with de novo deletion, the recurrence risk should be nearly zero. (2) In cases with familial translocation, risk estimates depend on the variable nature of the familial chromosome mutation. (3) If only one child is affected and has no deletion at 15q. this may be a sporadic or an isolated familial case. For this situation I estimated an overall recurrence risk of 0.4%. (4) If two or more sibs are affected, I consider a risk of 50% that the next sib may also be affected. This estimate reflects the observed segregation ratio and is in accordance with the proposed genomic imprinting model in the etiology of PWS. Prenatal cytogenetic diagnosis in a pregnancy at risk for PWS is hampered since del(15q) is almost exclusively found in sporadic cases. Hence, this method is limited to those very rare cases where del(15q) is due to familial structural chromosome rearrangements. An increasing number of DNA probes mapped to the Prader‐Willi chromosome region is available, but there is still no practical experience with family studies and prenatal diagnosis.
Retinitis pigmentosa, AD type I: exclusion of linkage to D3S47 (C17) in a large South African family of British origin
Authors: Gresnbarg Jacquie , Babaya Michelle , Ramasar Raj , Beighton Pater
Published: July 2010

Linkage analysis has been performed on a large South African family of British origin in which 39 persons in 6 generations had early onset Type I autosomal dominant retinitis pigmentosa (ADRP). Tight linkage was excluded between the disease and the D3S47 locus on chromosome 3.

This finding is further evidence for genetic heterogeneity in ADRP.