bluuebunny/crossref_metadata_2025 huggingface dataset:
Search for three known mutations in the RYR1 gene in 48 Danish families with malignant hyperthermia
Authors: Fagerlund T. , Ørding H. , Bendixen D. , Berg K.
Published: July 2010

We have examined 48 Danish families in which malignant hyperthermia reactions have occurred, with respect to three of six published mutations in the gene for the calcium release channel of sarcoplasmic reticulum (the RYR1 gene) believed to cause malignant hyperthermia susceptibility in man. The mutations are Arg614Cys, also known as the “pig mutation”; Arg163Cys; and Ile403Met. The only mutation found was Arg163Cys, which was detected in only one family. The results of this study indicate that other mutations must underlie the disorder in most Danish malignant hyperthermia‐susceptible families, and that the “pig mutation” is not a frequent cause of malignant hyperthermia susceptibility in Denmark.
Clinical, ultrastructural and biochemical studies in two sibs with Ehlers‐Danlos syndrome type VI‐B‐like features
Authors: Oǧur Gönül , Baykan Nazan , De Paepe Anne , Steinmann Beat , Quatacker Jozef , Kuseyri Faik , Yüksel‐Apak Memnune
Published: July 2010

Two Turkish sibs with clinical features of Ehlers‐Danlos syndrome type VI‐B are presented. The hydroxylysine contents of dermis and gel electrophoresis of type I and type III collagen produced by fibroblasts were normal. Ultrastructural studies of skin collagen and elastic fibers showed discrete abnormalities. Other syndromes with similar clinical, biochemical and ultrastructural features are discussed.
Charcot‐Marie‐Tooth disease: molecular characterization of patients from Central and Southern Italy
Authors: Guzzetta V. , Santoro L. , Gasparo‐Rippa P. , Ragno M. , Vita G. , Caruso G. , Andria G.
Published: July 2010

The syndrome of peroneal muscular atrophy, or Charcot‐Marie‐Tooth (CMT), disease represents the most common inherited peripheral neuropathy, with a prevalence of about 1 per 2500. The disease is usually transmitted in an autosomal dominant fashion, although it can display all the mendelian patterns of inheritance. The chromosome 17‐linked form (CMT1a) appears to be the most common form of the disease in all the ethnic groups studied so far, Italians included, and is due to a tandem duplication in 17p11.2. In order to study the distribution of CMT types and to establish a genotype‐phenotype correlation in patients from Central and Southern Italy, we collected 19 CMT pedigrees diagnosed in the years 1992–1993. Simple tandem repeats (STR) polymorphism analysis with the marker RM11‐GT and Southern blotting with the probes pVAW409R3 and pVAW412 were performed, demonstrating a high prevalence (about 60%) or 17p duplication in the families studied. No clinical or electrophysiological differences were noted between CMT1 patients with or without 17p duplication, respectively. Two families affected by CMT2 showed no evidence of rearrangement at the D17S122 locus. These data are consistent with the hypothesis of a different molecular basis for CMT2.
Factors influencing whether or not couples seek genetic counselling: an explorative study in a paediatric surgical unit
Authors: Hobus Inge , Frets Petra G. , Duivenvoorden Hugo J. , Tibboel Dick , Niermeijer Martinus F.
Published: July 2010

To investigate the factors influencing whether or not couples seek genetic counselling, the parents of 37 children with a major congenital anomaly were interviewed at home. All the children had been admitted to the Intensive Care Unit (ICU) of the Department of Paediatric Surgery. After physical examination of the child, the consultant clinical geneticist stated that genetic counselling was indicated for the parents. Whether they sought genetic counselling was left to the parents to decide. Eighteen of the 37 parents had sought genetic counselling. Assessment of the joint influence of a number of factors revealed that two factors were separately paramount in distinguishing between couples who did seek genetic counselling and those who did not: whether parents considered genetic counselling useful in their case shortly after the birth of their affected child, and whether the couple was clearly and correctly informed about the indication for genetic counselling. The intention to have a subsequent pregnancy was not associated with whether or not couples sought genetic counselling. Loss of information was observed: 1/3 of the referrals for genetic counselling mentioned on the written consultation forms were not stated in the discharge letters. This loss of information could have been reduced by a) routinely including the indication for genetic counselling in the discharge letter and b) appointing a coordinating physician to ensure that the parents were informed clearly about the availability of genetic counselling. Resistance to genetic counselling needs to be respected by the physician. Exploring its background might help to reduce this resistance.
Psychosocial and sexual functioning in women with Turner syndrome
Authors: Pavlidis Karen , McCauley Elizabeth , Sybert Virginia P.
Published: July 2010

Survey data on the sexual and social functioning of 80 adult women with Turner syndrome are described, as well as data regarding health status and self‐concept. Each woman completed the Tennessee Self‐Concept Scale, sections of the Derogatis Sexual Functioning Inventory, and a questionnaire covering a wide range of demographic and medical information. The women with Turner syndrome reported lower self‐concept compared to a normative sample. Sexual attitudes, gender role identity, and body image were assessed. The women with Turner syndrome tended to exhibit more conservative sexual attitudes and a more negative body image. In contrast to a normative sample, the women with Turner syndrome were less likely to have been sexually active. In addition, those currently involved in a stable relationship reported a lower frequency of sexual intercourse compared to a normative sample, although they generally reported moderate to high levels of sexual satisfaction. Regression analyses revealed that health status was associated with self‐concept, and that sexual satisfaction was related to both a higher frequency of intercourse and a higher self‐reported health status.
Mild cystic fibrosis disease in three Mexican delta‐F508/G551S compound heterozygous siblings
Authors: Orozco Lorena , Lezana José Luis , Villarreal María Teresa , Chávez Margarita , Carnevale Alessandra
Published: July 2010

We describe three delta‐F508/G551S compound heterozygous siblings with a mild CF phenotype, characterized by mild chronic pulmonary disease, pancreatic sufficiency and increased sweat chloride levels. PCR‐mediated site‐directed mutagenesis detected the delta‐F508 mutation on one allele, and the G551S mutation was detected by SSCP and sequence analysis of exon 11. Two previously described sisters who were homozygous for the G551S mutation had a very mild phenotype with normal sweat chloride concentrations. In our patients the mild phenotype resulted from the combined effect of the mild G551S allele with the severe delta‐F508 allele.
Autosomal recessive retinitis pigmentosa locus maps on chromosome 1q in a large consanguineous family from Pakistan
Authors: Leutelt Jutta , Oehlmann Ralph , Younus Farah , van den Born L. Ingeborgh , Weber James L. , Denton Michael J. , Mehdi S. Qasim , Gal Andreas
Published: July 2010

A large Pakistani family with several consanguineous marriages is described, in which autosomal recessive retinitis pigmentosa is segregating. Linkage studies revealed close linkage between the disease locus and six loci on chromosome 1q (D1S158, F13B, D1S422, D1S412, D1S413, and D1S53) with maximum lod scores ranging from 0.988‐4.657 at Θ=0.065‐0.235. However, the analysis of individual nuclear families showed very close linkage without recombination in three branches and several recombinants and negative lod scores throughout in the fourth branch. These results strongly suggest that mutations of two different genes are responsible for the disease in the ‘linked’ and ‘unlinked’ branches. Parallel to the linkage heterogeneity, clear phenotypic differences have been observed among the ‘linked’ and ‘unlinked’ parts. Our findings demonstrate that in case of recessive disorders the possibility of non‐allelic genetic heterogeneity should always be considered, even within the same kindred and in genetic isolates if a largely extended pedigree is analysed.
Event‐related potentials (ERPs) and intelligence in neonatally identified 47, XXY males
Authors: Netley C. , Taylor M. J. , Moland M.
Published: July 2010

The event‐related potentials (ERPs) of 18 extra X males (mean age 18.1 years) were recorded during the course of phonemic and orthographic discrimination tasks. The N2 and P3 latencies and amplitudes of subjects were examined in relation to their verbal and nonverbal intelligence test scores based on assessments at three ages: prior to puberty, during puberty and at sexual maturity. The results indicated that verbal abilities at most test occasions were significantly related to P3 latencies. Nonverbal abilities were largely uncorrelated with ERPs. The findings suggest that the verbal deficits of extra X males are the result of unlateralized individual differences in neural cognitive processing
Confidentiality in counseling for X‐linked conditions
Authors: Schaap Tamar
Published: July 2010

Genetic counseling in a synthetic fragile‐X family is used to illustrate some dilemmas which may arise from the genetic counselor's wish to respect the patient's confidence. What is the counselor's obligation towards family members who are unaware that they are carriers? Should the counselor try to avoid disclosing information concerning such family members to the patient, and if so ‐ how? May the future father of an affected fetus be prevented from participating in the reproductive decisions concerning that fetus, out of respect for the mother's wishes?
Variable expression of the popliteal pterygium syndrome in two 3‐generation families
Authors: Soekarman D. , Cobben J. M. , Vogels A. , Spauwen P. H. , Fryns J. P.
Published: July 2010

Three successive generations in two families affected with the popliteal pterygium syndrome are reported. While expression of the syndrome was relatively mild in the first and second generation, the patients in the third generation showed the full‐blown syndrome. Differential diagnosis between mildly affected patients with the popliteal pterygium syndrome and those with Van der Woude syndrome is difficult and may even be impossible. The present observations further support the hypothesis that both syndromes may in fact represent variants of the same condition.
Problems arising in correlating clinical and molecular data in myotonic dystrophy
Authors: Giordano M. , De Angelis M. S. , Cantello R. , Abdirisak N. A. , Mutani R. , Richiardi P. Momigliano
Published: July 2010

The number of copies of CTG trinucleotide repeats in the myotonic dystrophy gene correlates to a certain degree with the clinical symptoms in the patient. Routine molecular analysis of myotonic dystrophy is performed on peripheral blood cells, detecting the size of the expansion in leukocytes. However, in some cases somatic mosaicism is responsible for the presence of differently sized myotonic dystrophy alleles in different tissues of the same affected individual, complicating diagnosis and prognosis. Here we report two cases in which the correlation between molecular and clinical analysis performed with standard procedures posed some interpretative problems. The first individual was affected by an atypical clinical picture of myotonic dystrophy, the severity of which was not correlated with the low number of triplet repeats detected in his leukocyte DNA. The second case illustrates a prognostic problem in the presence of a low degree expansion in leukocytes. These examples outline the limits of standard molecular and clinical analysis in myotonic dystrophy.
Identification of a breast tumor with microsatellite instability in a potential carrier of the hereditary non‐polyposis colon cancer trait
Authors: Bergthorsson Jon Thor , Egilsson Valgardur , Gudmundsson Julius , Arason Adalgeir , Ingvarsson Sigurdur
Published: July 2010

Allelic expansion at microsatellite loci in colorectal tumor DNA indicates a genomic instability caused by defects in DNA mismatch repair. This is observed in a high proportion of tumors from individuals affected by hereditary non‐polyposis colorectal carcinoma, but to a lesser extent in sporadic colorectal tumors. In this study we screened 46 colorectal tumors for replication errors (RER). Tumors from six patients were found to be RER positive, two of which had a marked family history of colon cancer. In both cases the RER+ phenotype was detected in colon tumors from other family members, suggesting a germline mutation in mismatch repair genes. Additionally, RER+ phenotype, distinct from that of the colon and sporadic breast tumors, was found in malignant breast tissue from the mother of one proband.
Retinoblastoma in association with the chromosome breakage syndromes Fanconi's anaemia and Bloom's syndrome: clinical and cytogenetic findings
Authors: Gibbons Barbara , Scott David , Hungerford John L. , Cheung Kan Luk , Harrison Christine , Attard‐Montalto Simon , Evans Miles , Birch Jillian M. , Kingston Judith E.
Published: July 2010

Two children presenting with sporadic unilateral retinoblastoma and exhibiting a high degree of chromosome breakage were noted to have unusual facies, microcephaly and abnormal skin pigmentation. In the first child the pattern of both spontaneous and mitomycin‐C‐induced chromosome breakage was characteristic of Fanconi's anaemia although the degree of breakage was extreme. She also exhibited a striking increase in X‐ray‐induced chromosomal damage in G0 lymphocytes as measured by dicentric formation and increase in chromatid‐type aberrations. She had a number of typical clinical features, including cafe‐au‐lait patches and abnormalities involving the kidney; however, she demonstrated neither the hypoplasia of radius and thumb nor the typical aplastic phase of this disorder. At age 22 months the child became anaemic with trilineage myelo‐dysplasia, which was rapidly followed by the development of acute myeloblastic leukaemia. The early onset (at age 4 months) of retinoblastoma may have been associated with the underlying genomic instability. The second child exhibited a pattern of chromosome breakage characteristic of Bloom's syndrome, in addition to a moderate increase in damage induced by mytomycin‐C. She had the typical stunted growth and malar hypoplasia of Bloom's syndrome although she did not demonstrate the frequently described erythematous ‘butterfly rash’. Although patients with Fanconi's anaemia and Bloom's syndrome are recognised to be at an increased risk of cancer, retinoblastoma has not previously been described in patients with either condition. We suggest that underlying recessive chromosome breakage syndromes may be underdiagnosed in paediatric cancer patients, with important implications for prognosis and genetic counselling.
A further report of Brachmann‐de Lange syndrome in two sibs with normal parents
Authors: Krajewska‐Walasek Matgorzata , Chrzanowska Krystyna , Tylki‐Szymańska Anna , Bialecka Magdalena
Published: July 2010

We report on a family in which a girl and a boy in the same sibship show variable manifestations of a less severe type of Brachmann‐de Lange syndrome without significant prenatal growth deficiency and reduction deformities of the forearms. Both parents are healthy and phenotypically normal, and no other family members are affected. All the affected sibs except one described so far with normal parents presented the severe type of Brachmann‐de Lange syndrome (now sometimes classified as type I: “classic” or “full” Brachmann‐de Lange syndrome), with major upper limb anomalies, severe growth and mental retardation and, frequently, early death. We discuss the possible role of genomic imprinting in the etiology of this syndrome.
Complexity of molecular genetics of dyslipidemia in a family highly susceptible to ischemic heart disease
Authors: Jensen H. K. , Hansen P. S. , Jensen L. G. , Kristensen M. J. , Klausen I. C. , Kjeldsen M. , Lemming L. , Bolund L. , Gregersen N. , Færgeman O.
Published: July 2010

In a Danish family highly susceptible to ischemic heart disease, hyperlipidemia did not simply cosegregate with a previously undescribed 10 bp deletion in the LDL receptor gene causing heterozygous familial hypercholesterolemia (FH). This mutation, designated as FH DK‐4, deletes 10 nucleotides from ex on 4 coding for the third cysteine‐rich repeat of the ligand‐binding domain. The resulting translational frameshift and stop codon corresponding to amino acid position 181 in the LDL receptor cDNA is predicted to result in a truncated LDL receptor protein. Several family members had hyperlipidemia and early onset of ischemic heart disease not due to the 10 bp deletion, and several family members had unexpectedly high serum lipoprotein(a) contributing to high concentrations of serum LDL cholesterol. The study illustrates important limitations and possibilities of molecular genetic diagnosis.
Clinical traits and molecular findings in 46,XX males
Authors: López Marisol , Torres Leda , Méndez Juan Pablo , Cervantes Alicia , Pérez‐Palacios Gregorio , Erickson Robert P. , Alfaro Guillermo , Kofman‐Alfaro Susana
Published: July 2010

46,XX maleness is characterized by the presence of testicular development in subjects who lack a Y chromosome. The majority of affected persons have normal external genitalia, but 10–15% show various degrees of hypospadias. Several hypotheses have been proposed to explain the etiology of this constitution: translocation of the testis‐determining factor (TDF) from the Y to the X chromosome, mutation in an autosomal or X chromosomal gene which permits testicular determination in the absence of TDF, and undetected mosaicism with a Y‐bearing cell line. We report the pheno‐typic data and results of molecular analyses performed in six sporadic Mexican males with 46,XX karyotype. Molecular studies revealed Yp sequences in two individuals (ZFY+SRY+) with different phenotypes, a third one presented with a smaller segment of Yp (ZFY–SRY+) and complete virilization, while the remaining three were Y‐negative and showed hypospadias. In all subjects a hidden mosaicism with a Y‐bearing cell line was ruled out due to the absence of Y‐centromeric sequences. Our data demonstrate that the phenotype does not always correlate with the presence or absence of Y‐sequences in the genome, and confirm that 46,XX maleness is a genetically heterogeneous condition.
Monozygotic twins concordant for Rubinstein‐Taybi syndrome: changing phenotype during infancy
Authors: Preis Sabine , Majewski F.
Published: July 2010

We describe monozygotic twin sisters concordant for Rubinstein‐Taybi syndrome diagnosed at the age of 10 weeks. The typical features of Rubinstein‐Taybi syndrome in early infancy increasingly developed towards the total “Gestalt” at the age of 2 years and 10 months.
Opitz BBBG syndrome: new family with late‐onset, serious complication
Authors: Schrander Jaap , Schrander‐Stumpel Connie , Berg Jelle , Frias Jaime L.
Published: July 2010

The Opitz BBBG syndrome is characterized by hypertelorism and (in male patients) hypospadias, in addition to a number of midline abnormalities: posterior laryngeal cleft, stridor, swallowing dysfunction, cardiac defects, imperforate anus, and urinary tract and CNS anomalies. Inheritance is autosomal dominant (McKusick number * 145410) with partial male sex limitation in most pedigrees. We report a Dutch family with Opitz BBBG syndrome in which the proband developed late‐onset symptoms of a structural laryngeal abnormality.
Southern analysis reveals a large deletion at the hypoxanthine phosphoribosyltransferase locus in a patient with Lesch‐Nyhan syndrome
Authors: Renwick P. J. , Birley A. J. , McKeown C. M. E. , Hultén M.
Published: July 2010

Whole genomic hprt clones were used in Southern analysis to screen the integrity of the hprt gene in a family that includes a patient with HPRT enzyme deficiency causal to Lesch‐Nyhan syndrome. A 5 kb DNA sequence deletion was found to have its endpoints in the first and third introns. The probes identified the carrier status of female family members, aided by an RFLP carried by the mother's normal X‐chromosome.
Congenital heart disease in the 48,XXYY syndrome
Authors: Meschede Dieter , Nekarda Torsten , Kececioglu Deniz , Löser Hermann , Vogt Johannes , Miny Peter , Horst Jürgen
Published: July 2010

We report on an infant with severe tetralogy of Fallot, bilateral preauricular pits, and a 48,XXYY chromosomal complement. This case and evidence collected from the literature suggest that congenital heart disease may occur in the 48.XXYY syndrome more frequently than currently appreciated.
Joint dislocation and cerebral anomalies are consistently associated with oral‐facial‐digital syndrome type IV
Authors: Digilio Maria Cristina , Giannotti Aldo , Pagnotta Gaetano , Mingarelli Rita , Dallapiccola Bruno
Published: July 2010

We present a female patient with the oral‐facial‐digital syndrome type IV. Our report, the tenth in the literature, describes the typical manifestations of the syndrome, combined with malformations and deformations which have not always been described in the previously reported cases. They include cerebral and renal anomalies, anal atresia and dislocation of elbows and knees.
Aplasia of the optic nerve in two cases of partial trisomy 10q24‐ter
Authors: Pfeiffer R. A. , Jünemann A. , Lorenz B. , Sieber E.
Published: July 2010

We report two cases with partial trisomy of 10q24.1‐ter with concomitant deficiency of 7pter and 4qter, which share aplasia of the optic nerve and malformation of the anterior chamber. A review of published observations of partial trisomies of 10q showed that abnormalities of the eye, and particularly of the orbital region, are frequent, but ophthalmological studies are lacking. We conclude that our findings demonstrate a major effect of this chromosomal imbalance.
Genetics in democratic societies ‐ the Nordic perspective
Authors: Berg K. , Pettersson Ulf , Riis Povl , Tranøy Knut Erik
Published: July 2010

This report, with its emphasis on consensus points in the deliberations of the First Bioethics Workshop under the auspices of the Nordic Genome Initiative (an activity under the Nordic Council through its Nordic Programme Committee for Biotechnology), presents a Nordic perspective on the international discussion of ethical and legal issues relating to genetic testing. The Nordic countries have important common denominators with respect to political structure, education, religion, languages, cultural traditions and attitudes towards human values. A comprehensive national health service exists in all Nordic countries and there are important common legal foundations with great similarities between countries. However, in areas related to biotechnology there are considerable legal differences, but these differences do not necessarily reflect differences in underlying principles. Important ethical principles relevant to genetic testing that are shared by the Nordic countries include the concept of social justice with great stress on equality of treatment, the right to autonomy, the right to full disclosure of test results, strict confidentiality with respect to test resulis, the requirement that participation in testing programs must always be voluntary and based on information, and a responsible balance between risks or inconveniences on one hand and benefits on the other.
Duplication Xp22.2 and pseudoisodicentric Yq detected by FISH and PCR in a sterile male
Authors: Palka G. , Calabrese G. , Mingarelli R. , Franchi P. Guanciali , Stuppia L. , Morizio E. , Peila R. , Antonucci A.
Published: July 2010

A chromosome mosaicism with two cell lines was diagnosed in a sterile man. One cell line had a 45,—Y, dup (X) (p22.2) karyotype and accounted for 83% of lymphocytes analyzed. Fluorescence in situ hybridization (FISH) analysis with specific X and Y probes excluded a translocation between the short arms of the X and Y chromosomes and showed that Xp duplication involved a region containing the DXS85 locus, distal to the ZFX and DSS sites. The other cell line consisted of a diploid karyotype with a rearranged Y chromosome, which was shown to be a pseudoisodicentric Yq by FISH. Moreover, FISH with a specific probe for the AZF locus and polymerase chain reaction using Yq SY108 and SY121 primers showed no signals for this region, possibly accounting for the azoospermia in this patient.
Muscle expression of glucose‐6‐phosphate dehydrogenase deficiency in different variants
Authors: Ninfali Paolino , Baronciani Luciano , Bardoni Alessandra , Bresolin Nereo
Published: July 2010

Muscle expression of G6PD deficiency has been investigated in Mediterranean, Seattle‐like and A‐variants. G6PD activity was detected in samples obtained from biopsies on the quadriceps muscle of seven males and one female. The type of genetic variant was determined by molecular analysis of DNA, extracted from blood samples. All variants showed the enzyme defect in muscle. A statistically significant relationship was found in the activity of G6PD between erythrocytes and muscle of the male subjects (r=0.968; p=0.00008). The equation for the best fit line was: Y=0.390X + 0.198. The results suggest that, for a given variant, the extent of the enzyme defect in muscle may be determined, using this equation, from the G6PD activity of erythrocytes.
Image quality in digital chromosome analysis systems
Authors: Nivall S. , Holmquist D. , Gustavsson T. , Wahlström J.
Published: July 2010

This paper reports on an investigation into the differences in image quality of different components used in a digital image processing system for chromosome analysis. As chromosome aberrations are important tools in the cloning of genes, it is important to know if the introduction of computerized analysis systems increases the risk of missing small aberrations. In this investigation the number of visible bands on a number of chromosomes has been used as a measure of quality. The images compared are microscope ocular images, photographs from a microscope builtin camera, digital images from a high and from a standard resolution camera, presented both on screen and print‐out on paper. The main conclusions are that: (1) the view in the microscope ocular gives the best resolution, (2) there are risks of losing vital information using the digital image processing system for chromosome analysis, and (3) this risk is significantly reduced when using a high resolution camera.
Apolipoprotein E allele frequencies in a South African Indian female population
Authors: Gounden Nirmala , Naidoo Jenisa , Pegoraro Rosemary J. , Berger G. Michael B.
Published: July 2010

Coronary heart disease is common amongst South Africans of Indian (Asian) ancestry. As part of an investigation into risk factors in premenopausal and post‐menopausal Indian nurses, we determined the apolipoprotein E genotype by means of restriction isotyping on 173 healthy nurses between the ages of 25–55 years. The apolipoprotein E allele frequencies on 346 chromosomes were: ε2, 1.2% (95% confidence interval 0.06‐2.66); ε3, 87.6% (95% confidence interval 84.1–91.1 and ε4, 11.3% (95% confidence interval 7.94‐14.60). No ε2/2 homozygotes were encountered. Our results demonstrate an extremely low frequency of the ε2 allele, a low‐normal apo ε4 and a high ε3 allele frequency. It is unlikely that apolipoprotein E polymorphism contributes to the high incidence of coronary heart disease in this population.
Pericentric inversions of chromosome 4: report of a new family and review of the literature
Authors: Villa A. , Urioste M. , Carrascosa M. C. , Vázquez S. , Martínez A. , Martínez‐Frías M. L.
Published: July 2010

A family was cytogenetically studied because of the birth of a male child with a multiple congenital anomaly pattern, in whom a dup (4q) recombinant was found. His phenotypically normal mother's karyotype showed an apparently balanced pericentric inversion in a chromosome 4. So as to analyze the occurrence of recombinants, the cytogenetic data from this family are compared with those of the 18 previously reported familial cases of pericentric inversions (PIs) of chromosome 4. The congenital anomalies observed in the child strongly suggest Wolf‐Hirschhorn syndrome but some of his clinical features seem to be pathogenetically related to the presence of lymphedema during the intrauterine period. In the multiple congenital anomaly pattern observed in this patient, the lymphedema could be the consequence of the large 4q duplication. The review of chromosome 4 PIs with 4q duplication suggests that the q3 region should be examined when edema is detected prenatally.
Increased frequency of apolipoprotein ε2 allele in non‐insulin dependent diabetic (NIDDM) patients with nephropathy
Authors: Eto M. , Horita K. , Morikawa A. , Nakata H. , Okada M. , Saito M. , Nomura M. , Abiko A. , Iwashima Y. , Ikoda A. , Makino I.
Published: July 2010

The genetic polymorphism of apolipoprotein E (ε2, ε3 and ε4) is associated with lipid abnormalities. It has been suggested that lipid abnormalities may contribute to the development and progression of kidney diseases, including diabetic nephropathy. Thus, in this study we compared the apo E allele frequencies among 146 non‐insulin‐dependent diabetic (NIDDM) patients with nephropathy, 135 NIDDM patients without nephropathy and 576 of the general Japanese population. The ε2 allele frequency was significantly higher in diabetic patients with nephropathy (7.2%) and with renal failure (9.7%) than in diabetic patients without nephropathy (2.6%) and in the general Japanese population (3.7%). It is concluded that there is a possibility that the ε2 allele is associated with nephropathy in NIDDM.
Increased and decreased relative risk for noninsulin‐dependent diabetes mellitus conferred by HLA class II and by CD4 alleles
Authors: Ghabanbasani Mahdi Zamani , Spaepen Marijke , Buyse Inge , Legius Eric , Decorte Ronny , Bex Maddy , Marynen Peter , Bouillon Roger , Cassiman Jean‐Jacques
Published: July 2010

Non‐insulin‐dependent diabetes mellitus has been recognized to be heterogeneous in etiology, with multiple subgroups. Several genes or chromosomal regions have been implicated in the development of the disease. In this study the association of HLA class II alleles and genotypes and the association of CD4 and CD3 polymorphisms were assessed in a large number of Belgian non‐insulin‐dependent diabetes mellitus patients. Furthermore, the importance of the DQα***Arg52/DQαlArg52 and the DQβlAsp57/DQβlAsp57 genotypes and the combination of both genotypes were examined. Our results show that in the HLA class II genes only the DQαlArg52+/DQαlArg52+ genotype was significantly associated with non‐insulin‐dependent diabetes mellitus compared with controls (p=0.011, RR=2.02). We also observed that the frequency of the CD4*A4/*A8 genotype and the CD4*A7 allele was significantly increased and decreased respectively in non‐insulin‐dependent diabetes mellitus patients as compared with the controls (p=0.018, RR=2.16 and p=0.0003, RR=0.49 respectively). These results therefore suggest that HLA class II and CD4 genes might independently contribute to the susceptibility for non‐insulin‐dependent diabetes mellitus and that these alleles and genotypes might identify subgroups of patients with different susceptibilities.
Clinical overlap of Beckwith‐Wiedemann, Perlman and Simpson‐Golabi‐Behmel syndromes: a diagnostic pitfall
Authors: Verloes Alan , Massart Brigitte , Dehalleux Isabelle , Langhendries Jean‐Paul , Koulischer Lucien
Published: July 2010

We report on a child who died in the neonatal period. Major external anomalies included foetal overgrowth, macroglossia, and ambiguous genitalia (micropenis and perineoscrotal hypospadias with cryptorchidism). Necropsy showed a large right diaphragmatic hernia, visceromegaly, multicystic kidney dysplasia, Langerhans islet hyperplasia, nephroblastomatosis, multiple adrenal adenomas, and dysplastic testicles. The child illustrates the difficulties of the differential diagnosis of overgrowth syndromes in the neonatal period, and the phenotypic overlap of Beckwith‐Wiedemann, Denys‐Drash, Simpson‐Golabi‐Behmel, Perlman and possibly Meacham‐Winn syndromes. Simpson‐Golabi‐Behmel syndrome was felt to be the most likely diagnosis. If this opinion is correct, genital ambiguity, hydramnios and nephroblastomatosis should be added to the clinical spectrum of Simpson‐Golabi‐Behmel syndrome. Differential diagnosis between the above‐mentioned syndromes is of major importance for accurate genetic counseling, considering the differences in recurrence risk. The present case underlines the need for longterm survey of patients suspected of having Simpson‐Golabi‐Behmel syndrome, who could be at risk for embryonic tumours.
Haspeslagh syndrome without severe mental retardation and pterygia?
Authors: van Bever Yolande , Hennekam Raoul C. M.
Published: July 2010

An adult female is described with mild developmental delay, typical facies, dental anomalies, arachnodactyly and camptodactyly. In many respects she resembles four other patients described earlier, but differs in not having multiple pterygia, nor severe mental retardation. We suggest that this entity should be named Haspeslagh syndrome. The differential diagnosis is discussed.
Gorlin‐Chaudhry‐Moss or Saethre‐Chotzen syndrome?
Authors: Preis Sabine , Kaewel E.‐V. , Majewski F.
Published: July 2010

We report a 2‐year‐old girl with craniosynostosis, an ossification defect of the cranial vault, midface hypoplasia, low frontal hairline, anti‐mongoloid slant of the palpebral fissures, ptosis of the lateral upper lids and high‐arched narrow palate. There are additional findings fitting the Gorlin‐Chaudhry‐Moss syndrome, such as hypoplasia of the labia majora, hypoplasia of the distal phalanges of fingers and toes and conductive hearing loss, but hypertrichosis and dental anomalies are missing, which were described in the four females previously reported with the probably autosomal recessive Gorlin‐Chaudhry‐Moss syndrome. Since the autosomal dominant Saethre‐Chotzen syndrome may show similar craniofacial features, short fingers with non‐obligatory cutaneous syndactyly, and ossification defects of the cranial vault, the Saethre‐Chotzen syndrome should also be considered in our patient.
A simple method to detect the RYR1 mutation G1021A, a cause of malignant hyperthermia susceptibility
Authors: Alestrøm A. , Fagerlund T. H. , Berg K.
Published: July 2010

To search for the mutations RYR1 G1021A in families where malignant hyperthermia (MH) episodes have occurred, we have used an amplificationcreated restriction sites (ACRS) technique to detect the mutation. The previously described single‐stranded conformation polymorphism (SSCP) technique was laborious and time consuming, but necessary to detect the mutation, whereas the method described here discriminates quickly and efficiently between homozygotes with the mutation, heterozygotes and homozygotes without the mutation.
Prenatal cystic fibrosis screening in a low‐risk population undergoing chorionic villus sampling for fetal karyotyping
Authors: Brambati B. , Anelli M. C. , Tului L.
Published: July 2010

Screening for cystic fibrosis (CF) has been offered to pregnant women seeking chorionic villus sampling (CVS) for prenatal chromosomal abnormality investigation. The mutation panel has increased over the years to include 8 mutations and can detect 65% of abnormal CF genes in the Italian population. Testing was offered to a total of 2214 consecutive pregnant women; 45 of them declined screening (take up rate: 98%). In 1055 of the 2169 pregnancies screened, the test was at first done on the fetus, while in the remaining cases both parents were investigated. Among parents 46 carriers were identified (2.1%), in 41 of whom the mutation was delta F508. In two couples both parents were heterozygous, and in one the fetus was affected and the pregnancy was terminated. Although CF testing offered to pregnant women undergoing invasive investigation such as CVS may not be the model for a mass screening, its very high effectiveness can represent an advantageous component of more comprehensive strategies.
Seven DNA polymorphisms in the LDL receptor gene: application to the study of familial hypercholesterolemia in Spain
Authors: Chaves F. Javier , Puig Oscar , Garcia‐Sogo Magdalena , Real José , Gil José V. , Ascaso Juan , Carmena Rafael , Armengod M. Eugenia
Published: July 2010

We have performed restriction fragment length polymorphism (RFLP) analysis at the low density lipoprotein receptor (LDLR) locus in order to investigate the molecular genetics of familial hypercholesterolemia (FH) in Spain. Firstly, a sample of 50 unrelated patients with a clinical diagnosis of FH was screened for the presence of major rearrangements at this locus by Southern blot analysis of BgtII digested genomic DNA. Four different mutations were detected, accounting for 8% of the mutant alleles in the Spanish FH sample. Then, we determined the relative allele frequency and estimated linkage disequilibrium between seven RFLPs of the LDLR gene in the remaining 46 FH patients and in 61 normolipidemic controls. Hindi, Avail, PvuII, MspI, and NcoI are the most polymorphic sites with individual PIC values higher than 0.28, whereas the TaqI and StuI sites display low levels of polymorphism. The usefulness of the seven RFLPs to confirm a clinical diagnosis of FH was investigated in 15 FH‐families, consisting of 118 individuals, in whom the presence of Familial Defective Apolipoprotein B‐100 (FDB) due to the apoB3500 mutation was excluded. Independent haplotypes were constructed for 71 chromosomes: 15 FH and 56 control haplotypes. A total of 14 different haplotypes was found. In 12 families, clinical diagnosis of FH was confirmed by cosegregation analysis, which makes these RFLPs useful for studying the inheritance of the LDLR gene in 80% of Spanish families with FH. Comparison of haplotypes found in the Spanish sample with those found in Swiss and Norwegians suggests heterogeneity of haplotypes among European populations.
High levels of Lp(a) lipoprotein in a family ith cases of severe pre‐eclampsia
Authors: Husby Henrik , Roald Borghild , Schjetlein Rune , Nesheim Britt‐Igjerd , Berg Kåre
Published: July 2010

We report a family with two cases of severe pre‐eclampsia/eclampsia in which very high levels of Lp(a) lipoprotein were found. The serum level of Lp(a) lipoprotein is genetically determined and the Lp(a) apolipoprotein has a close homology to plasminogen. Very high levels of Lp(a) lipoprotein might interfere with the fibrinolytic/thrombolytic process in man. A previous report suggested that a high maternal serum Lp(a) lipoprotein level can cause fetal growth retardation, and it is proposed that very high levels might lead to increased deposition of fibrin in the uterine spiral arteries in pregnancy, which is central in the pathogenesis of pre‐eclampsia. If confirmed, a very high Lp(a) lipoprotein level could be one risk factor for pre‐eclampsia that is genetically determined.
Two brothers with multiple congenital anomalies and mental retardation due to disomy (X)(q12 → q13.3) inherited from the mother
Authors: Apacik C. , Cohen M. , Jakobeit M. , Schmucker B. , Schuffenhauer S. , und Taxis E. Thurn , Genzel‐Boroviczeny O. , Stengel‐Rutkowski S.
Published: July 2010

We present the phenotypic, cytogenetic and molecular findings in two dysmorphic and mentally retarded brothers with disomy Xq12→q13.3. The mother and the grandmother carry the same rearrangement of the X chromosome, which was interpreted as an inverted insertion of the segment (X)(q12→q13.3) into Xq21.2. The X‐inactivation‐specific‐transcript (XIST) is expressed in the probands' mother but is absent in her son, confirming the hypothesis that X inactivation is realized only if two X inactivation centers reside on different X‐chromosomes (trans‐configuration). In the phenotypically normal mother the aberrant X chromosome was late replicating in all cells, indicating functional monosomy of the constitutional segment trisomy. The phenotype of the brothers is considered to be the consequence of a functional disomy Xq12→q13.3. The trait combination observed in the brothers was compared with the spectrum of clinical and anthropological traits for proximal Xq disomy in males, elaborated by phenotype analyses of the available literature cases.
Exclusion of Treacher Collins Franceschetti syndrome in a subject with tetralogy of Fallot and cryptorchidism
Authors: Bruni Lida , Angeletti Barbara , Pascale Esterina , Tozzi Maria Cristina , Giammaria Paola , Verna Roberto , D'Ambrosio Ettore
Published: July 2010

Genotyping with flanking DNA markers was used to ascertain Treacher Collins Franceschetti syndrome (TCOF1) in a subject affected by tetralogy of Fallot and cryptorchidism. The proband's family consisted of a father and sister who were affected by the disease, and a healthy mother. Since cardiac malformation and cryptorchidism have been associated with the TCOF1 syndrome, the proband was suspected to be a carrier of the mutated gene. Microsatellite markers D5S527, SPARC and D5S519, which previously mapped the TCOF1 gene within a 2.1‐cM interval on chromosome 5 (5q32–33.1), were used to follow the transmission of the TCOf 1 mutated locus. Flanking markers D5S519 and D5S527 were informative and enabled us to exclude inheritance of a TCOF1 mutation to the proband, while showing that cardiac malformation and cryptorchidism were unrelated in mis patient.
The evaluation of gonosomal mosaics: lymphocyte interphase nuclei analyzed by FISH
Authors: Schliephacke M. , Maier C. I. M. , Majlinger G. , Tomiuk J. , Leipoldt M. , Kaiser P.
Published: July 2010

The reliable evaluation of chromosomal mosaics is still considered to be difficult in clinical diagnosis if aberrant metaphases are only present at low frequencies. Classical cytogenetic findings cannot significantly exclude low mosaic levels, obviously, because of the relatively low number of analyzed metaphases. To study this problem, the number of gonosomes in lymphocyte interphase nuclei was determined by FISH (fluorescence in situ hybridization) application of two satellite DNA probes, DXZ1 and DYZ1. The results obtained with this method from lymphocytes of clinically and cytogenetically inconspicuous persons showed a high degree of reliability. The DNA probe yielded correct signals in more than 95% of the analyzed nuclei. Additionally, patients were examined who showed cytogenetically confirmed numerical gonosome aberrations. These results were compared with those obtained from the control group of inconspicuous patients and discussed with respect to the evaluation of gonosomal mosaics.
Molecular characterization of 21p‐variant chromosome
Authors: Conte Robert A. , Mathews Thomas , Kleyman Svetlana M. , Verma Ram S.
Published: July 2010

Fortuitously, within a 1‐month period, we were referred two individuals for routine cytogenetic amniocenteses involving one chromosome 21 from each patient, which had apparently lost the entire short arm and a major portion of the centromeric alphoid sequences in their amniocytes. Breakage may have occurred within alphoid sequences resulting in extreme variants. Variations of a similar nature were originally referred to as Christchurch (Ch1) chromosomes and have been wrongly determined to be abnormal. The 21p—chromosome variants were similar in both cases, though they are from unrelated individuals. These rare variants, whose origins were both maternal and have no clinical consequences, were characterized by the FISH‐technique to provide a greater degree of certainty.
Chromosome 22q11 deletion and other chromosome aberrations in cases with cleft palate, congenital heart defects and/or mental disability. A survey based on the Danish Facial Cleft Register
Authors: Brøndum‐Nielsen Karen , Christensen Kaare
Published: July 2010

Velo‐cardio‐facial syndrome (VCFS) is a syndrome associated with haploinsufficiency of genes at chromosome 22q 11. The syndrome has a broad phenotypic spectrum including multiple anomalies, of which cleft palate (CP), congenital heart defects (CHD), and mental disabilities are among the most common. Hence, a high prevalence of 22ql 1 deletions should be expected among cases with a combination of CP and CHD or/and mental disability. In Denmark a population‐based database comprising 2301 CP cases born 1936–1987 has been established. Cases with CP and CHD or/and mental disabilities were selected from the register. By using public registers 39 living cases were identified, among whom 15 agreed to blood sampling and testing for 22q11 deletion using FISH (fluorescence in situ hybridization) analysis. Four deletion cases were identified. Using a polymorphic microsatellite marker (D22S264), two cases were shown to be de novo deletions of maternal origin. The parental origin in the two other cases could not be determined. The patients ranged in age from 7 to 40 years. All patients had mental impairment, and one also showed signs of paranoid psychosis. Two cases had CHD. Furthermore, five cases previously karyotyped had other chromosomal aberrations. The study shows that facial cleft registers are an obvious source for identifying a group of patients with a high risk of VCFS and chromosome 22ql 1 microdeletion. These individuals as well as their families can benefit from genetic counselling.
Agenesis of the corpus callosum in Schinzel‐Giedion syndrome associated with 47, XXY karyotype
Authors: Özkinay F. Ferda , Akisü Mete , Kültürsay Nilgün , Oral Resmiye , Tansug Nermin , Sapmaz Gül
Published: July 2010

The Schinzel‐Giedion syndrome is a rare autosomal recessive condition with typical facial features, skeletal manifestations and congenital hydronephrosis and/or hydroureter. We report a male infant with Schinzel‐Giedion syndrome, also showing the karyotypic abnormality 47, XXY. Agenesis of the corpus callosum and laryngeal stenosis were determined at autopsy. Besides typical Schinzel‐Giedion syndrome, our propositus was found to be affected by Klinefelter syndrome. This represents a fortuitous anomaly, which is probably of no importance in the phenotype of the patient.
A concealed penis mimicking penile agenesis in an infant with trisomy 13
Authors: Chen Chih‐Ping , Liu Fen‐Fen , Jan Sheau‐Wen , Su Tsung‐Hsien , Lan Chung‐Chi
Published: July 2010

Penile agenesis results from failure in the development of the genital tubercle and is rarely associated with chromosomal abnormalities. We report on an echographic prenatal diagnosis of penile agenesis associated with trisomy 13. At birth, the contour of the penile shaft and the glans could not be seen. However, a careful palpation allowed us to determine that the penile shaft was concealed and normal in size, rather than penile agenesis being present. To our knowledge, a concealed penis associated with trisomy 13 has not previously been described.
Short rib‐polydactyly syndrome in twins: Beemer‐Langer type with poly dactyly
Authors: Elçioǧlu Nursel , Karatekin Güner , Sezgin Betül , Nuhoǧlu Asiye , Cenani Asim
Published: July 2010

We present premature female twin fetuses with concordant extremely shortened ribs, short limbs, macrocephaly, median cleft upper lip and facial dysmorphism. Based on radiological criteria and the pattern of associated abnormalities, a lethal short rib‐polydactyly syndrome (Beemer‐Langer type) was diagnosed. The differential diagnosis of this entity is discussed.