bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between low density lipoprotein receptor (LDLR) and apolipoprotein E (apoE) alleles contributes to normal variation in lipid level
Authors: Pedersen Jan Chr. , Berg Kåre
Published: July 2010

Subjects drawn from a population‐based register were studied with respect to lipid level association. The association of isoforms of apolipoprotein E (apoE) with lipid level in the general population was found to be limited to people with one particular genotype at the low density lipoprotein receptor (LDLR) locus. The results presented in this paper suggest that functional LDLR variants enhance or limit the effect of isoforms of apoE. The association between apoE4 and serum total and LDL cholesterol level may be mediated through the LDL (apoB100, apoE) receptor to a greater extent than previously thought.
Non‐allelic mutations in X‐linked retinitis pigmentosa
Authors: Chen J. D. , Dickinson P. , Gray R. , Constable I. , Sheffield L. , Denton M. J.
Published: July 2010

Using RFLP studies, the disease locus in two X‐linked retinitis pigmentosa families was found to be centromeric to DXS7 in one family and telomeric to DXS7 in another, suggesting nonallelic heterogeneity.
The de Lange syndrome. Report of 15 cases
Authors: Filippi Giorgio
Published: July 2010

Fifteen cases of the de Lange syndrome are presented. Personal and family histories, clinical features, detailed radiological findings, laboratory data, chromosome studies and dermatogly‐phic patterns are reported. A Negro patient and his autopsy findings are described. Radiological diagnostic features are stressed; in particular, the combined presence of a hypoplastic middle phalanx of the index fingers and variable short metatarsal appear to be two additional features which are diagnostically helpful. The etiology of the syndrome is unknown; however, there is some evidence to suggest a genetic basis. The literature is briefly reviewed.
The mutation mechanism causing juvenile‐onset Tay‐Sachs disease among Lebanese
Authors: Hechtman P. , Boulay B. , Bayleran J. , Andermann E.
Published: July 2010

Expression of the hexosaminidase isozymes was evaluated in fibroblast cell lines obtained from two sibs of Lebanese‐Christian origin who presented with juvenile‐onset Tay‐Sachs disease. In the normal control fibroblasts the α subunit of hexosaminidase A (hex A) is synthesized as a 67 KD precursor which is cleaved in lysosomes to a mature 54 KD peptide. The patients' fibroblasts were capable of synthesizing the 67 KD precursor but failed to convert it to the mature subunit. The α subunit precursor synthesized by patients' cells could not be phosphorylated, nor was the patients' α subunit precursor secreted into the medium in response to NH4Cl, which caused accumulation of both α and β subunit precursor in the medium of the normal control fibroblasts. The measurement of residual enzyme activity in the fibroblasts of patients which best correlated with the onset of the illness was the ion exchange chromatographic separation of Hex A‐associated hydrolysis of the synthetic substrate 4‐methylumbelliferyl N‐acetyl‐β‐D‐glucosamine‐6‐sulfate (4MUGS). The patients had 0.32% and 0.36% of Hex Aassociated 4MUGS cleaving activity compared to normal control fibroblasts as compared to <0.016% for infantile Tay‐Sachs disease fibroblasts. The residual Hex A activity in patients cells had a pH optimum identical with normal enzyme (pH 3.9–4.0), a reduced specific activity for 4MUGS (relative to hydrolysis of unsulfated synthetic substrate), and a greatly enhanced thermal stability. The occurrence of this form of Tay‐Sachs disease in Lebanon, the fact that the condition has been described in three unrelated Lebanese immigrant families in Canada, together with the fact that the grandparents of the unrelated probands come from villages in both the northern and southern regions of Lebanon, leads us to speculate that a gene causing juvenile‐onset Tay‐Sachs disease may not be infrequent in Lebanon.
Chondrodysplasia punctata in an adult recognized as vitamin K antagonist* embryopathy
Authors: Hosenfeld D. , Wiedemann H.‐R.
Published: July 2010

A 32‐year‐old man with disproportionate short stature and striking facial dysmorphism came to genetic counseling as his wife was expecting their first child. In early infancy he had been diagnosed as having chondrodysplasia punctata, later regarded to be the autosomal dominant hereditary form. The expectant father was therefore convinced of a high risk of recurrence and vacillated between thoughts of taking his own life and of having his wife's pregnancy terminated. When his history revealed recurrent thromboses in his mother, treated with anticoagulants during pregnancy, her medical records of 1953 were located, and they disclosed that she had been treated with phenprocoumon (Marcoumar®) from the 8th to the 12th and from the 13th to the 15th weeks of pregnancy. The patient has since become the father of a healthy son.
A case of de novo trisomy 12p syndrome
Authors: Tayel Shawky , McCorquodale M. M. , Rutherford T. , Kurczynski T. W. , Abdel‐Aziz Adel M. , El‐Gabaldy Farid , Sharaf E. A.
Published: July 2010

A case of pure 12p trisomy was discovered in a 14‐year‐old boy during a cytogenetic survey of Egyptian students attending a school for mentally retarded children. The patient had a normal birth weight but later showed developmental delay. Clinical examination at 14 years of age revealed a high bulging forehead, broad and flat nasal bridge, large mouth with everted lower lip, folded upper ear helix with protuberant antihelix, pectus excavatum, undescended testes, flat feet, generalized hypotonia and moderate mental retardation. Chromosomes analyzed from blood lymphocytes showed an enlarged short arm with an additional band on one of the no. 12 chromosomes. The duplicated chromosomal material extended from 12pter→p12.2, including the LDH‐B locus, which showed a gene‐dosage effect. This extra chromosomal material arose de novo by tandem duplication. The parents' chromosomes were normal.
Duchenne muscular dystrophy:detection of deletion carriers by spectrophotometric densitometry
Authors: Laing Nigel G. , Siddique Teepu , Bartlett Richard , Yamaoka Larry H. , Hung Wu‐Yen , Pericak‐Vance Margaret A. , Roses Allen D.
Published: July 2010

DNA isolated from a family segregating a deletion in the Duchenne muscular dystrophy gene and control families was digested with restriction enzymes, Southern transferred, and probed with a radioactive dystrophin cDNA probe. The resulting autoradiographs were analyzed with a densitometric spectrophotometer to detect carriers of the deletion. The carrier status of females in the deletion pedigree was independently determined by genomic probes and confirmed by densitometry. In many Duchenne families, deletions will only be observed using cDNA probes which show few restriction fragment length polymorphisms (RFLPs). Such deletions would normally have to be detected using dosage gels. The spectrophotometric densitometry technique used by us does not require dosage gels, and avoids problems arising from non‐informative meioses and cross‐overs. It should be possible to screen every family with an exon deletion by spectrophotometric densitometry provided the presently available cDNA is suitably reduced to produce fewer bands on autoradiographs.
Determining zygosity in the Vietnam Era Twin Registry: an approach using questionnaires
Authors: Eisen S. , Neuman R. , Goldberg J. , Rice J. , True W.
Published: July 2010

The Vietnam Era Twin Registry (VETR) is a registry of 7375 American male veteran twin pairs born between 1939 and 1955 who served in the armed forces of the United States between 1964 and 1975. Optimal use of registry data requires the determination of zygosity. Two approaches are available: analysis of blood genetic marker systems and responses of twins to questions about sibling similarity. Zygosity for the VETR was determined using the questionnaire technique supplemented with blood group typing data abstracted from military records. After comparing four alternative zygosity assignment methods, a logistic regression technique which uses discriminating variables based on race was selected. The approach is similar to that described by Magnus et al. (1983) in their study of Norwegian twins, suggesting that questionnaire responses are independent of nationality and reinforcing the reliability of the questionnaire method for zygosity ascertainment.
“Variability gene” effect of cholesteryl ester transfer protein (CETP) genes
Authors: Berg Kåre , Kondo Ikuko , Drayna Dennis , Lawn Richard
Published: July 2010

Cholesteryl ester transfer protein (CETP) may have important roles in transfer of lipids from cells to serum lipoproteins or between circulating lipoprotein particles. Restriction fragment length polymorphisms (RFLPs) in DNA at the CETP locus have been detected. In the present study we have used RFLPs detectable with the restriction enzyme TaqI to examine if CETP influences serum lipid variability (as opposed to absolute lipid levels). We have compared within‐pair difference in serum lipid and apolipoprotein levels in monozygotic twin pairs of various genotypes in the B polymorphism at the CETP locus and uncovered significant differences between genotypes. We conclude that the CETP locus has “variability genes” (as opposed to “level genes”) with respect to total and LDL cholesterol variability. A person's total genetic risk for coronary heart disease may depend on his or her combination of “level genes” and “variability genes”. The method of analysis applied may be the best available for the study of gene ‐ environment interaction.
X‐linked hypohidrotic ectodermal dysplasia and t(X;12) in a female
Authors: Turleau Catherine , Niaudet P. , Cabanis Marie‐Odile , Plessis Ghislaine , Cau D. , de Grouchy J.
Published: July 2010

A female patient with features of hypohidrotic ectodermal dysplasia (HED) was found to be a carrier of a de novo t(X;12) with a breakpoint in Xq13.1. This is the second instance of an X/autosome translocation, with apparently the same X breakpoint, reported in HED.
Linkage studies of Myotonia congenita and Paramyotonia congenita
Authors: Bender K. , Senff H. , Steiert A. , Lagodny H. , Wenker T. F. , Koch M.
Published: July 2010

Six German families segregating for Myotonia congenita (MC) and eight families from Germany and Great Britain with Paramyotonia congenita (PC) were tested for linkage relationships using 35 serological and biochemical markers. No linkage of MC to any of the markers was evident, but a positive sum of lod scores for PC vs. the HP locus (ẑ= 1.16, θ=0.16) was found. The results encourage further investigations involving chromosome 16 markers.
Catalase and glutathione peroxidase activity in cells with trisomy 21
Authors: Crosti N. , Bajer J. , Gentile M. , Resta G. , Serra A.
Published: July 2010

CuZnSOD is produced in overdose in cells with trisomy 21.

This has been considered to be a cause of increased oxidative stress. In the present work we have studied the catalase and glutathione peroxidase activity in fibroblasts from 6, and blood cells from 30, subjects affected by Down syndrome. In the fibroblasts, catalase and glutathione peroxidase activities did not differ significantly from control cells. In platelets, lymphocytes, polymorphs and erythrocytes, no significant increase of catalase activity was found while glutathione peroxidase activity appeared significantly increased in platelets, polymorphs and erythrocytes but not in lymphocytes. These data seem to indicate that the increase of CuZnSOD in trisomy 21 cells does not affect the production of catalase. An increase, instead, of glutathione peroxidase has been detected in all blood cells, except in lymphocytes; this is a sign of a greater need for protection against the risk of lipoperoxidation. The fact that the enhancement of glutathione peroxidase activity could be assessed only in some types of cells examined suggests that the observed increase in those cells is probably a result of an additive effect of the overproduction of CuZnSOD due to gene dosage and the ordinarily higher content of oxygen radicals and peroxides.
Haplotype analysis of the phenylalanine hydroxylase gene in Turkish phenylketonuria families
Authors: Stuhrmann M. , Riess O. , Mönch E. , Kurdoglu G.
Published: July 2010

We have estimated the haplotype distribution of mutant and normal phenylalanine hydroxylase (PAH) alleles for 17 Turkish phenylketonuria (PKU) families: 20 normal and 27 mutated PAH alleles could be identified. Of the latter, the most prevalent were associated with haplotype 6 (29.6%), 1 (18.5%) and 36 (11.1%), while the normal alleles were preferentially associated with haplotype 1 (20%). Of the 19 different haplotypes observed, 5 have not been described previously. The haplotype distribution differed significantly from that of the Northern European population. Two of the eight polymorphic sites were in association with PKU. No deletions of exon sequences were found in the families analysed.
The effect of consanguinity on the reproductive wastage in the Turkish population
Authors: Basaran N. , Hassa H. , Basaran A. , Artan S. , Stevenson J. D. , Sayli B. S.
Published: July 2010

Analysis of data from 56664 marriages in Turkey studied from 1970 to 1988 showed an overall rate of consanguineous marriages, of 21.25%, and increases in the rates of abortions, stillbirths, prenatal losses and neonatal deaths.
Batten disease (Spielmeyer‐Sjogren disease) and haptoglobins (HP): indication of linkage and assignment to chr. 16
Authors: Eiberg H. , Gardiner R. M. , Mohr J.
Published: July 2010

In a material of 26 Caucasian families, 23 with at least 2 children affected with Batten disease, we found a lod score of 3.00 at theta=0.00 in males and theta=0.26 in females with haptoglobin (HP), and assign the locus for Batten disease to 16q22.
Identification of a second “French Canadian” LDL receptor gene deletion and development of a rapid method to detect both deletions
Authors: Yuanhong MA  , Bétard Christine , Roy Madeleine , Davignon Jean , Kessling Anna M.
Published: July 2010

Hobbs et al. (N. Engl. J. Med. 317: 734–737, 1987) reported a large deletion of approximately 10 kilobases in the 5′ portion of the human low‐density lipoprotein (LDL) receptor gene. This deletion affects about 60% of familial hypercholesterolemia (FH) heterozygotes in the French Canadian population. We have developed a rapid, convenient method for the detection of the deletion using double digestion with the restriction enzymes Xbal and EcoRV, or triple digestion with Xbal, EcoRV and XmnI, and a 650 bp cDNA probe, radio‐labeled using a random oligonucleotide primer technique. Eighty French Canadian FH heterozygotes were screened for the presence of the deletion. Forty‐seven (59%) of them were found to carry the 10 kb deletion. Using the same method, we also identified a new mutation which was found in four of the 80 (5%) FH patients. This mutation has been found to be a 5 kb deletion removing exons 2 and 3 of the LDL receptor gene, which correspond to the first two repeats of the LDL receptor binding domain. Cosegregation of the 5 kb deletion and the FH phenotype was observed in one family. Possible structure‐function relationship is discussed.
DNA polymorphisms at fibrinogen loci and plasma fibrinogen concentration
Authors: Berg K. , Kierulf P.
Published: July 2010

Associations have been reported between restriction fragment length polymorphisms (RFLPs) at fibrinogen loci and plasma fibrinogen concentration, in a British study. We have examined a series of unrelated Norwegians. We found no association between plasma fibrinogen concentration and any genotype in either of two fibrinogen polymorphisms examined (one at the α‐fibrinogen locus, the other at the β‐fibrinogen locus). We have also examined monozygotic twins and evaluated heritability of fibrinogen level by the intraclass correlation coefficient. We arrived at an unimpressive estimate of heritability. With such a low level of heritability, it would have been surprising if we had found an association with a single gene marker in a relatively limited series of people. The reason for the discrepancy between the British and the Norwegian study is unknown. Great care has to be exercised in interpreting disease associations, since with DNA variations being examined at an increasing number of “candidate loci”, the risk of finding spurious associations increases with the number of analyses conducted.
Autosomal dominant polycystic kidney disease in the 1980's
Authors: Dalgaard Ole Zeuthen , Nørby Søren
Published: July 2010

Since it is one of the commonest hereditary diseases, causing serious illness in adulthood, autosomal dominant polycystic kidney disease (ADPKD) is a problem for both the affected families and for the health economy of the society. The current management of ADPKD is reviewed with emphasis on the development of predictive DNA analyses, the recently discovered genetic heterogeneity, and ethical perspectives. Insurance aspects are discussed, and the need for access to selective reproductive prevention as well as for improvement of conventional therapeutic measures is stressed.
Environmental health hazard handling: statistical and strategic concerns
Authors: Hilden Jørgen
Published: July 2010

Some key issues in industrial and environmental health risk research and the ensuing political decision process are discussed, with particular emphasis on statistical trouble spots: the acceptable risk concept; the welfare of future generations; burden of proof; research priorities; public visibility of risks and benefits; statistical extrapolations; multiple testing. The “tiny thief phenomenon, discussed in detail, is the paradoxical fact that an almost harmless chemical may steal more of our health than a grossly hazardous chemical because the former is allowed to operate over a disproportionately long time span before being detected, if ever. The difficulty of proving that something is safe is reviewed. Finally, it is urged that politicians be taught the facts of scientific, including statistical, life; likewise, scientists should be made aware of the nature of political decision processes. Otherwise scientists will emigrate from health hazard research into areas of science where equivocal results and political interference are less common.
Genetic epidemiology of Greenland
Authors: Harvald Bent
Published: July 2010

The Inuit (Eskimo) gene pool is in many respects similar to that of East Asian populations. Some polymorphisms imply frequent occurrence of disorders comparatively rare in Western Europe (e.g. lactose and sucrose malabsorptions). Low frequencies of alleles for slow isoniazid acetylation and sparteine/debrisoquine oxidation indicate slow elimination of a multitude of drugs. Autoimmune disorders (e.g. rheumatoid arthritis, insulin‐dependent diabetes mellitus, Graves' disease and psoriasis) are rare, possibly explained by the associations of these disorders with HLA‐alleles rare in the Inuit (e.g. HLA‐B8). A correspondingly high incidence of reactive arthritis may be explained by a frequent HLA‐B27 allele. The prevalence of disorders due to instability of mesenchymal tissues (e.g. spondylolisthesis, osteoarthrosis, hernia, heart block) still requires a biochemical explanation. Attention is drawn to the urgency of genetic studies in the Arctic because of the accelerating hybridization of the Inuit in all circumpolar areas.
A familial chromosomal translocation t(6q;7q) with habitual abortions
Authors: Zhang Sizhong , Wu Xiaoyan , Ho Qun , Zhao Li
Published: July 2010

A familial balanced translocation between the long arms of chromosomes 6 and 7 is described. The break points are localized to 6q27 and 7q23. No phenotypical abnormalities were found in any of the three carriers, but spontaneous abortions were frequent and might be associated with the translocation due to unbalanced segregation.
The inactivation of the fragile X chromosome in female carriers of the Martin Bell syndrome as studied by two different methods
Authors: Tuckerman E. , Webb T.
Published: July 2010

Female heterozygotes for the fragile X syndrome show variable levels of mental handicap from normal to severely retarded. The degree to which they are affected may depend upon whether the fragile or the normal X chromosome is preferentially inactivated, but one of the problems with the use of BUdR for the study of Lyonisation in fragile‐X heterozygotes is that it reduces the level of expression of the fragile site. Results obtained by this method will be biased if the suppression occurs preferentially in either the active or the inactive X chromosome. To confirm that BUdR does not preferentially cause repair of the fragile site on either the late or the early replicating X chromosome, a comparison was made between the percentage of active or early fragile‐X obtained using BUdR, and that obtained using tritiated thymidine in cells from the same heterozygote.
Diagnostic molecular genetics of the fragile X
Authors: Sutherland Grant R. , Mulley John C.
Published: July 2010

The approaches to carrier detection and prenatal diagnosis of the fragile X syndrome using DNA probes are described. Since the definitive diagnosis rests upon the cytogenetic demonstration of the fragile X, molecular diagnoses are essentially confined to fragile X family members in whom the fragile X cannot be demonstrated. Since none of the polymorphic probes available are tightly linked to the fragile X, the preferred approach is to use probes which flank the fragile site. Useful probes are listed and suggested recombination fractions for use in diagnosis are given. A strategy is outlined for obtaining the closest informative flanking markers with the minimum amount of laboratory effort. Methods of risk analysis are discussed. It is concluded that molecular analysis is very useful for carrier detection but of limited use in prenatal diagnosis.
Consanguinity and the genetic control of Down syndrome
Authors: Hamamy Hanan A. , Al‐Hakkak Zuhair S. , Al‐Taha Salma
Published: July 2010

Eighty‐three infants and children with a professional diagnosis of Down syndrome were studied cytogenetically. The results showed that 81.9% of them were trisomy 21 and 18.1% were the 46/47 + G type of mosaic. All cases were distributed according to parental consanguinity. The results showed that 77.9%, 16.2% and 5.9% of the trisomy 21 cases, and 53.3%, 26.7% and 20.0% of the mosaic cases were from non‐consanguineous, First‐cousin and second‐cousin marriages, respectively. By combining all the cases, these percentages were 73.5%, 18.1% and 8.4%, respectively. Considering the high rate of inbreeding in Iraq (inbreeding coefficient = 0.0225) and using various statistical comparisons, these results revealed the lack of evidence for genetical control of non‐disjunction in man.
Skin mastocytosis with short stature, conductive hearing loss and microtia: a new syndrome
Authors: Wolach B. , Raas‐Rothschild A. , Metzker A. , Choc L. , Straussberg R. , Lew S. , Goodman R. M.
Published: July 2010

A 5‐year‐old Sephardic Jewish girl, born of consanguineous parents, is described. She has short stature, microcephaly, conductive hearing loss, skin mastocytosis and microtia. Since this constellation of findings has not been reported previously, we think that these findings represent a new congenital malformation, most probably of genetic etiology.
Use of the RB1 cDNA as a diagnostic probe in retinoblastoma families
Authors: Goddard Audrey D. , Phillips Robert A. , Greger Valerie , Passarge Eberhard , Höpping Wolfgang , Zhu Xiaoping , Gallie Brenda L. , Horsthemke Bernhard
Published: July 2010

Use of an intragenic BamHI restriction fragment length polymorphism within the 5′ end of the retinoblastoma gene (RBI) provided improved genetic counselling for five familial and ten non‐familial retinoblastoma patients and their relatives. All other polymorphic probes within RBI were uninformative in three families, and accuracy of diagnosis was improved by use of this polymorphism in two families. In 10/14 informative constitutional DNA‐RB tumor DNA pairs, a reduction to homozygosity allowed identification of the RBI allele at risk to carry a germline RBI mutation.
Inherited quantitative DNA variation in the LPA (“apolipoprotein (a)”) gene
Authors: Kondo Ikuko , Berg Kåre
Published: July 2010

The Lp(a) antigen resides in a polypeptide chain that is attached to apolipoprotein B (apoB) by a disulfide bridge. Recently, cDNA for this polypeptide chain (frequently referred to as the Lp(a) polypeptide chain, Lp(a) apolipoprotein or apolipoprotein (a)) was cloned and extensive homology to plasminogen was uncovered. This homology creates significant difficulties in studying DNA variation in the gene (the LPA gene) for this polypeptide and the plasminogen gene. We have studied a variant 2 kilobase (kb) DNA fragment detectable after digestion with the restriction enzyme MspI, which appears to originate from the LPA gene since it is detected by LPA probes but not with plasminogen probes. It is related to the “kringle IV” region of the LPA gene since it is detected with an LPA probe that only contains “kringle IV” repeats. A proportion of people appears to lack (or have an undetectable level of) the 2 kb fragment and there are significant quantitative differences between samples from people who have the fragment. Presence and amount of this fragment appear to segregate in families as a Mendelian trait. This quantitative DNA variation is likely to reflect differences between individuals in number of “kringle IV” repeats at the LPA locus.
Prenatal diagnosis in Pelizaeus‐Merzbacher disease using RFLP analysis
Authors: Mäenpää Johanna , Lindahl Elina , Aula Pertti , Savontaus Marja‐Liisa
Published: July 2010

Pelizaeus‐Merzbacher disease (PMD) is a rare X‐linked recessive disorder with severe psycho‐motor retardation and neurological symptoms due to an inborn abnormality of proteolipid protein (PLP), the major protein component of myelin. A tight linkage between the gene of PLP and PMD locus has been suggested. We have carried out a series of RFLP studies using a cDNA probe for PLP and an anonymous DNA‐fragment DXYS12 in a large Finnish family with at least three affected individuals. DNA analysis on chorionic villus specimens allowed us to exclude the disease in a male fetus of a possible carrier mother and, likewise, to demonstrate carrier status in a female fetus in another at‐risk pregnancy.
CSF and urine biogenic amine metabolites in Rett syndrome
Authors: Lekman Annika , Witt‐Engerström Ingegerd , Holmberg Berit , Percy Alan , Svennerholm Lars , Hagberg Bengt
Published: July 2010

The metabolites of dopamine (homovanillic acid ‐ HVA), noradrenaline (4‐hydroxy‐3‐methoxy‐phenylglycol ‐ HMPG), and serotonin (5‐hydroxyindoleacetic acid ‐ 5‐HIAA) were measured in cerebrospinal fluid (CSF) from 38 patients and urine from 36 patients with typical Rett syndrome (RS) and compared with controls of similar age. CSF metabolite concentrations were the same in the patients and controls. Urinary metabolites expressed per mol creatinine were significantly higher in older RS patients. This difference is partly explained by lower urinary creatinine levels in older RS patients, due to their known reduction in muscle mass. Alterations in CSF or urine biogenic amine metabolite concentrations do not appear to represent the primary abnormality in RS, and their measurement cannot be regarded as a reliable means of diagnosis.
Apolipoprotein A‐l/C‐lll gene cluster polymorphism in Saudi Arabians, Filipinos and Caucasians
Authors: Johansen Klaus , Skotnicki Antoni , Tan Jenny C. Y. , Kwaasi Aaron A. A. , Skotnicki Mary
Published: July 2010

We studied the polymorphic locus in the A‐I/C‐III gene cluster on the long arm of chromosome 11 in 147 Saudi Arabian, in 84 Filipino and in 69 Caucasian blood donors. Digestion of DNA yielded two fragments 4.2 kb and 3.2 kb long. The genotypic distribution was the same in Arabs and Filipinos, but both were significantly different from Caucasians (p = 0.005 and 0.0005). The 3.2‐kb allele occurred in 18% of the Saudi Arabians, in 23% of the Filipinos and in 4% of Caucasians. The frequency of the 3.2‐kb allele was significantly higher in Arabs and Filipinos compared to Caucasians (p = 0.0005).
Sotos syndrome and de novo balanced autosomal translocation (t(3;6)(p21;p21))
Authors: Schrander‐Stumpel C. T. R. M. , Fryns J. P. , Hamers G. G.
Published: July 2010

In this report we describe a 6‐year‐old boy with Sotos syndrome and a de novo apparently balanced 3/6 translocation (karyotype: 46,XY,t(3;6)(p21;p21)). Pre‐ and postnatal overgrowth are observed in an increasing number of conditions of variable etiology. In the Sotos syndrome autosomal dominant inheritance with variable expression has been documented. Here we discuss the importance of the cytogenetic findings and postulate a relationship between the invisible loss of chromosomal material at 3p21 and/or 6p21 and the expression of the autosomal dominant gene.
The female and the fragile X syndrome: data on clinical and psychological findings in 7 fra(X) carriers
Authors: Borghgraef M. , Fryns J. P. , van den Berghe H.
Published: July 2010

In this report we present precise data on the clinical, intellectual and behavioural findings in 7 young fra(X) positive girls. The two most common and most important findings are an overgrowth syndrome present from birth on and common behavioural features like severe attentional problems and extreme shyness and anxiety. These symptoms seem to constitute the major criteria for fra(X) screening in prepubertal girls. The findings in previous studies are compared with the present observations.
A familial interstitial deletion of the long arm of chromosome 21
Authors: Roland B. , Cox D. M. , Hoar D. I. , Fowlow S. B. , Robertson A. S.
Published: July 2010

A mother and daughter with an interstitial deletion of the chromosome segment 21q11 to 21q2l.3 have similar minor dysmorphism and mild mental retardation. These two patients are compared to others in the literature with deletion of the same region of chromosome 21. Molecular analysis of DNA from our patients localizes the DNA segments D21S1, D21S11, D21S8, and D21S22 within the deleted region.
The cis‐configuration effects of rare chromosomal fragile sites
Authors: Côté Gilbert B.
Published: July 2010

Rare chromosomal fragile sites may adversely affect specific alkies of closely linked genes when in cis‐configuration. This is illustrated by data published in Sutherland & Hecht (1985) on chromosome 16 at band q22.1.
Retinitis pigmentosa: genetic mapping in X‐linked and autosomal forms of the disease
Authors: Humphries Peter , Farrar G. Jane , Kenna Paul , McWilliam Peter
Published: July 2010

Retinitis pigmentosa (RP) is an hereditary degenerative disease of the retina and a major cause of visual impairment, prevalence estimates ranging from 1 in 3000 to 1 in 7000. The condition may segregate as an autosomal dominant, autosomal recessive or an X‐linked recessive trait and it may also occur on a sporadic basis in up to 50% of cases. In the autosomal dominant form, close linkage to the DNA marker C17 (D3S47) was recently established in a large family of Irish origin displaying early‐onset disease (McWilliam et al. 1989), multipoint analysis indicating the gene for rhodopsin as a likely candidate (Farrar et al. 1990). In that gene, a C→A transversion in codon 23, resulting in a proline→histidine substitution has now been identified in 17 of 148 unrelated ADRP patients in the United States (Dryja et al. 1990). This mutation is absent however in the original Irish pedigree (it is also absent in 21 other dominant Irish pedigrees, representing approximately 70% of the estimated ADRP population) indicating that another mutation, either in rhodopsin itself, or in a gene very closely linked to rhodopsin is responsible for the disease in that family. Analysis of other dominant pedigrees using the C17 and/or rhodopsin probes has indicated either tight linkage (Bhattacharya, Personal Communication), looser linkage, possibly indicative of a second locus on 3q (Olsson et al. 1990) or no linkage (Farrar et al. 1990, Blanton et al. 1990, Inglehearn et al. 1990). Extensive genetic heterogeneity thus exists in the autosomal dominant form of this disease, and in the light of these new observations, earlier tentative evidence for linkage of ADRP to the Rhesus locus on chromosome I will be re‐evaluated. A locus for type II Usher syndrome (classical RP combined with congenital pedial deafness, and normal vestibular function) has now been established on the long arm of chromosome 1 (Kimberling et al. 1990). Type I Usher families, in which hearing loss is more profound and vestibular function absent, do not segregate with the same chromosome 1q markers, indicating the existence of another, as yet unlocated gene. In the X‐linked form of the disease, two genes, XLRP2 and XLRP3, have been located on the proximal short arm of the X chromosome using a combination of physical and linkage mapping techniques, and there is some evidence to suggest a possible third locus more distally located. Advances thus being made, in the localization, isolation and characterization of RP‐causing genes, are likely radically to extend our knowledge of the molecular pathology of this prevalent group of conditions over the next few years.
Analysis of mosaic states in amniotic fluid using the in‐situ colony technique
Authors: Welborn Jeanna L. , Lewis Jerry P.
Published: July 2010

Appropriate counselling and clinical management of the pregnant woman with a mosaic amniotic fluid cell karyotype are difficult. The majority of the data on mosaicism and pseudomosaicism are derived from studies employing the flask technique for the analysis of amniotic fluid cell cultures. Since the majority of laboratories now utilize the in‐situ technique, such data may not be relevant when analyzing results from the in‐situ colony technique. We reviewed the incidence of mosaicism in 6339 amniotic fluid samples using the in‐situ technique. Data are presented on the types of aberrations and clinical outcomes. A classification of mosaicism is presented that distinguishes mosaicism of clinical importance from that which is obviously of extrafetal origin or artifactual. This approach clarifies the significance of mosaic states detected by the in‐situ colony technique and provides a rational foundation for genetic counselling and for planning clinical interventions.
Time trends (1980–1987) of ten selected informative morphogenetic variants in a newborn population
Authors: Merlob P. , Aitkin I.
Published: July 2010

The annual prevalence rates of ten selected informative morphogenetic variants (IMVs) were studied in 31 194 newborn infants over a period of 8 years (1980–1987). Two of them (preauricular sinus and ocular hypertelorism) revealed a highly significant decrease by logistic regression analysis. The other eight presented a stable pattern or small fluctuations which did not reach statistical significance. These data may serve as valuable baseline rates for monitoring IMVs in a specific newborn population. Their potential informative value as indicators of altered morphogenesis and their power for monitoring programs of environmental teratogenicity should be carefully verified.
Amelogenesis imperfecta with taurodontism and the tricho‐dento‐osseous syndrome: separate conditions or a spectrum of disease?
Authors: Crawford Peter J. M. , Aldred Michael J.
Published: July 2010

Various authors have allocated a diagnosis of tricho‐dento‐osseous syndrome to cases originally reported as amelogenesis imperfecta (hypomaturation‐hypoplasia type) with taurodontism. The resulting confusion has prompted this critical review of the literature, and further information has been obtained from the authors concerned. Criteria for diagnosis of the two conditions are proposed.
Spinal muscular atrophy type I combined with atrial septal defect in three sibs
Authors: Møller P. , Moe N. , Saugstad O. D. , Skullerud K. , Velken M. , Berg K. , Nitter‐Hauge S. , Børresen A.‐L.
Published: July 2010

All three children of an unrelated Norwegian couple were born with spinal muscular atrophy (SMA I) as confirmed by autopsy in two of them. Two of the children died at birth, whereas one lived for 7 weeks on support systems that included artificial ventilation. All three children had large atrial septal defects (ASD). One had valvular aortic stenosis. Another had arrhinencephaly and transient pleural effusion which was evacuated during pregnancy. The findings may reflect concurrence of unrelated disorders caused by genetic or environmental factors, segregation of linked genes, pleiotropism or the existence of a previously unknown disease.
Exclusion mapping of 12 X‐linked disease loci and 10 DNA probes from the long arm of the X‐chromosome
Authors: Yang H.‐M. , Lund T. , Niebuhr E. , Nørby S. , Schwartz M. , Shen L.
Published: July 2010

Specific chromosome rearrangements associated with disease entities are invaluable resources for physical mapping. A deletion on the X chromosome of a male leads to the nullisomy for X‐linked genes, resulting in the onset of genetic diseases and/or the absence of the DNA probe detectable sequences. This permits the localization of these loci within the deleted area. On the other hand, the region for some other X‐linked loci can be excluded from the deleted area according to the absence of the characteristic symptoms of the disease and/or the presence of the hybridization signals. An interstitial deletion on the long arm of the X chromosome of a male has been characterized by high resolution banding. The karyotype of the proband is 46,Y,del(X)(pter→q21.1::q21.33→qter). The regions for 12 X‐linked disease loci as well as 10 DNA probes are excluded from the deleted area, and localized either proximally or distally to the deletion. The results also reveal a controversy in the present linkage data concerning the assignment of these loci.
Morphologic variants in parents of children with malformation syndromes: are they indicators of somatic mosaicism?
Authors: Méhes Károly , Kosztolányi György
Published: July 2010

The ostensibly normal parents of 27 probands with recessive or sporadic multiple malformation syndromes were reexamined. By means of careful investigations and anthropometric measurements in nine of them, morphologic variants were found that were compatible with the syndromes and were also observed in the proband. Although other factors should also be considered, the findings may be explained by germline and somatic mosaicism in the parents.
Disomic balanced reciprocal translocation
Authors: Wilmot Patrick L. , Shapiro Lawrence R. , Casamassima Anthony C.
Published: July 2010

The previously unreported and unique finding of a complete disomy of an apparently balanced reciprocal translocation is described. The parents are second cousins once removed and each parent contributed the same balanced reciprocal translocation chromosome. Although the complete disomy involves balanced translocation chromosomes from unaffected parents, it is possible that a hemizygous state of some genes may be present on each translocation chromosome, which in a disomic homozygous state could result in an abnormal phenotype, as manifested by infantile seizures in this patient.
Incontinentia pigmenti: XXY male with a family history
Authors: García‐Dorado J. , de Unamuno P. , Fernández‐López E. , Veloz J. Salazar , Armijo M.
Published: July 2010

We report on the case of a male who from the start of life displayed vesicular lesions; on the trunk these were clustered and on the limbs they adopted a linear configuration. After biopsy of one such lesion, the histopathological study was compatible with a diagnosis of incontinentia pigmenti (IP). In the following months, hyperkeratotic lesions appeared which later became pigmented. The mother and other female members of the family also showed different degrees of alteration related to the same disease. The karyotype study showed the existence of 47,XXY (Klinefelter syndrome). The exceptional nature of this case is that although it is the third case reported in the literature of a male affected by incontinentia pigmenti with a previous family history, it is the only one combining this characteristic with the presence of a 47,XXY karyotype.
The Proteus syndrome: association with nephrogenic diabetes insipidus
Authors: Hotamisligil Gökhan S. , Ertogan Fadil
Published: July 2010

In this report we present the first case of Proteus syndrome associated with nephrogenic diabetes insipidus. The case is a 9‐month‐old girl, with macrodactyly of both feet and left hand, syndactyly of the 3rd and 4th fingers of the left hand, soft tissue masses in the paravertebral and gluteal regions, and a hyperpigmented epidermal nevus with hyperkeratosis on the left half of the body.
Friedreich's ataxia: a descriptive epidemiological study in an Italian population
Authors: Leone Maurizio , Brignolio Francesco , Rosso Maria Gabriella , Curtoni Emilio Sergio , Moroni Antonio , Tribolo Antonella , Schiffer Davide
Published: July 2010

All the cases of Friedreich's ataxia (FA) diagnosed between 1945 through 1984 among residents of a defined area of northwestern Italy were ascertained (N = 59). Cases were diagnosed according to the criteria of the “Quebec Cooperative Study on Friedreich's Ataxia (QCSFA)” with minor modifications. We identified 39 families with 47 probands and 12 secondary cases. Therefore ascertainment probability was 80%. Male to female ratio was 1:1. Pedigrees were compatible with autosomal recessive inheritance. Segregation ratio was 0.28 with both Weinberg's method and the “singles” method (under incomplete ascertainment). Point prevalence ratio was 1.2/100 000 population. Birth incidence rate was 1/36 000 live births. Gene frequency was estimated to be 1/191. The ratio of first‐cousin marriages observed among parents of FA patients (3%) was lower than expected from Dahlberg's formula (8%). This finding is not compatible with the hypothesis of genetic heterogeneity for FA.
Very early onset Huntington's disease: genetic mechanism and risk to siblings
Authors: Clarke David J. , Bundey Sarah
Published: July 2010

A study of very early onset Huntington's disease (VEOHD) has shown that at least 38% of gene‐carrying sibs also develop symptoms before the age of 10, thus improving the genetic risk for those sibs who remain healthy. The prevalence of VEOHD among sibs shows that mutation during spermatogenesis is most unlikely to account for these uncommon cases. The data suggest that two mechanisms contribute to VEOHD: modification by many genes (individually of small effect), and an epigenetic mechanism occurring when transmission is through a series of males.
Bone marrow transplantation in canine GM1 gangliosidosis
Authors: O'Brien John S. , Storb Rainer , Raff Robert F. , Harding Jane , Appelbaum Frederick , Morimoto Satoshi , Kishimoto Yasuo , Graham Ted , Ahern‐Rindell Amelia , O'Brien Susan L.
Published: July 2010

Allogeneic bone marrow transplantation was carried out in an 81‐day‐old Portuguese water dog with GM1 gangliosidosis using a DLA identical sibling as donor. Engraftment was complete and β‐galactosidase activity in leukocytes of the transplanted dog were similar to those in the donor. Over the next 2.5 months neurological deterioration in the transplanted dog was similar to that in untreated dogs with GM1 gangliosidosis. Cerebral ganglioside GM1 concentrations were not diminished by bone marrow transplantation and cerebral β‐galactosidase activity was negligible. We conclude that allogeneic bone marrow transplantation early in life is ineffective in canine GM1 gangliosidosis.
Brachy/ectrodactyly and absence or hypoplasia of the fibula: an autosomal dominant condition with low penetrance and variable expressivity
Authors: Genuardi M. , Zollino M. , Bellussi A. , Fuhrmann W. , Neri G.
Published: July 2010

A complex dysostosis characterized by brachy‐ and/or ectrodactyly and fibular hypoplasia was found in two distantly related individuals. The proposita, aged 25 years, showed metacarpal and phalangeal hypoplasia on both hands, ectrodactyly on both feet, and nearly complete bilateral absence of the fibula. Only milder acromelic defects were detected in a second cousin. A similar pattern of skeletal involvement had been previously described in an unrelated Italian family. The peculiar segregation pattern can be explained by autosomal dominant inheritance with low penetrance and variable expressivity.
Fetal hydrops in Sardinia: implications for genetic counselling
Authors: Galanello R. , Sanna M. A. , Maccioni L. , Gasperini D. , Melis M. A. , Rosatelli C. , Monni G. , Cao A.
Published: July 2010

This paper describes the first case of Hb Bart's hydrops fetalis syndrome in the Sardinian population. Despite the high frequency of α‐thalassemia, fetal hydrops is extraordinarily rare in the Sardinian population because α‐thalassemia is more usually the result of the single α‐thalassemia globin gene deletion and is very rarely produced by the deletion of two α‐globin genes. The fetus, the product of a consanguineous marriage at risk for β‐thalassemia, was monitored by chorionic villi DNA analysis which detected the heterozygous state for the codon 39 nonsense mutation. Follow‐up ultrasound examination showed fetal hydrops, which led us to carry out further investigation. Hemoglobin and α‐globin gene analysis on cord blood obtained by cordocentesis revealed the homozygous state for the most common deletion α°‐thalassemia in Mediterranean populations. Retrospective evaluation of the father's hematological features showed very low MCH‐MCV for a β‐thalassemia carrier which may indicate coinherited α‐thalassemia. These findings indicate that careful evaluation of red cell indices of parents at risk for β‐thalassemia and adequate consideration of the consanguinity may point to co‐inherited α‐thalassemia and lead to the appropriate analysis.
Genetic marker family studies in familial Mediterranean fever (FMF) in Armenians
Authors: Shohat T. , Petersen G. M. , Sparkes R. S. , Langfield D. , Bickal J. , Korenberg J. R. , Schwabe A. D. , Rotter J. I.
Published: July 2010

Familial Mediterranean fever is an autosomal recessive disease manifested by recurrent short episodes of fever associated with polyserositis. It is common in a variety of Mediterranean and near Eastern populations. The biochemical defect is unknown, and there have been few studies of genetic marker associations or linkage with the disease. We have screened blood samples from members of 14 nuclear Armenian families, the population with the highest known gene frequency, for 19 different polymorphic phenotypic genetic markers. These 14 families included 31 affected and 43 unaffected family members. No association was found with any of the markers studied. Linkage could be excluded at the distance of 0–15% recombination with 14 markers. Linkage could not be excluded with 5 other markers. These results exclude the FMF gene from those portions of the human gene map that are at least 0.5% recombination distance from these 14 genetic markers, and represent the first comprehensive step in the eventual localization and isolation of the FMF gene.
Primordial osteodysplastic dwarfism type I in association with corneal clouding: evidence for autosomal recessive inheritance
Authors: van Maldergem L. , Gillerot Y. , Godhaird M. , Nemec E. , Koulischer L.
Published: July 2010

A newborn male, born to Turkish first cousins, presented with severe pre‐ and postnatal growth retardation. Weight was 800 g at term. Salient clinical features were dwarfism with moderate limb shortening, microcephaly, hirsutism, facial dysmorphism including prominent small cloudy eyes, large nose with high nasal root, retrognathism and low‐set ears. Radiologic abnormalities included huge clavicles, dysplastic vertebrae and enlargement of proximal metaphyses with medial spurs.