bluuebunny/crossref_metadata_2025 huggingface dataset:
The motivation of at‐risk individuals and their partners in deciding for or against predictive testing for Huntington's disease
Authors: Evers‐Kiebooms G. , Swerts A. , Cassiman J. J. , Berghe H. Van Den
Published: July 2010

Sixty‐six percent of the at‐risk persons and 74% of the partners in a large survey in Belgium have the intention of making use of predictive testing for Huntington's disease. One third of them, however, have expressed the intention of postponing the final decision for various reasons. The intention to be tested is not at all related to sociodemographic characteristics. A thorough exploration of the reasons for being in favour of or against taking the test reveals that the motivation inspiring this very personal decision is very complex. In the group of at‐risk persons, less than half of the variation in the intention to be tested is explained by the role of a series of specific reasons as predictor variables in a regression analysis. The proportion of explained variation is slightly higher in the group of partners. ‘To have certainty about my own future’ and ‘to make arrangements for the future’ play a major part in the decision of the total group. ‘Making decisions concerning children’ and to a larger extent ‘informing children about their risk status’ are important factors in deciding in favour of the test.
Alpha‐fetoprotein findings in a case of cystic adenomatoid malformation of the lung
Authors: Albright Susan G. , Katz Vern L.
Published: July 2010

Cystic adenomatoid lesion of the lung is a rare and variable malformation of unknown etiology, which may be detected prenatally. This report details the prenatal ultrasound and amniotic fluid alpha‐fetoprotein findings in a 19‐week fetus with this malformation.
Ehlers‐Danlos syndrome: a new oculo‐scoliotic type with associated polyneuropathy?
Authors: Farag Talaat I. , Schimke R. Neil
Published: July 2010

Two siblings born to consanguineous Bedouin parents and grandparents are reported with the phenotypic features of Ehlers‐Danlos Syndrome (EDS), type VI. In addition, the affected individuals have a polyneuropathy as confirmed by nerve conduction velocity, electromyographic and muscle biopsy studies. We propose that this clinical combination represents a distinct type of EDS.
Genetic linkage between Huntington's disease and D4S10(G8) in Scottish families
Authors: Holloway Susan , Millan F. A. , Curtis Ann , Mennie Moira , Brock D. J. H.
Published: July 2010

Genetic linkage between Huntington's disease (HD) and polymorphic DNA markers at the D4S10 locus has been investigated in 16 Scottish families. A maximum lod score of 3.499 at a recombination fraction of 0.07 was found, with 95% confidence limits of 0.02 and 0.22. Only one obvious recombinant was detected, and the wide confidence limits probably reflect the large number of unaffected individuals whose risk could only be estimated empirically.
Chromosomal abnormalities in amniotic fluid cell cultures: a comparison of apparent pseudomosaicism in Chang and RPMI‐1640 media
Authors: Krawczun Michael S. , Jenkins Edmund C. , Masia Annette , Kunaporn Suphat , Stark Sandra L. , Duncan Charlotte J. , Sklower Susan L. , Rudelli Raoul D.
Published: July 2010

The finding of chromosome mosaicism is one of the most difficult problems in fetal chromosome analysis. Whether the finding indicates true mosaicism or pseudomosaicism must be investigated. Studies detailing the incidence of true mosaicism and pseudomosaicism have been reported (Hsu & Perlis 1984, Bui et al. 1984, Worton & Stern 1984) but do not correlate pseudomosaicism with any particular type of culture media. Benn & Hsu (1985) compared cell growth and chromosome abnormalities in amniotic fluid cell cultures grown in Chang medium and RPMI‐1640 medium and found no statistically significant difference in the rate of abnormalities in the two media. We have previously shown that Chang medium exhibited more abnormalities which were not verified in second and third cultures (Masia et al. 1986). In the current study we examined 212 cases grown in both Chang and RPMI‐1640 media, and compared apparent single and multiple cell pseudomosaic abnormalities to medium type. The number of observed abnormalities was 22, occurring in 19 of the cases studied. Apparent pseudomosaic chromosome anomalies were observed in 18 Chang cultures and in 4 RPMI‐1640 cultures. Statistical analysis found significant correlation between medium type and the degree of observed pseudomosaic cells. We conclude that the rate at which pseudomosaic cells are observed is partly a function of medium type, and in our laboratory Chang medium caused apparent pseudomosaicism at a greater level than RPMI‐1640 medium.
Phenotype variability in the Miller acrofacial dysostosis syndrome. Report of two further patients
Authors: Chrzanowska K. H. , Fryns J. P. , Krajewska‐Walasek M. , Wisniewski L. , Van den Berghe H.
Published: July 2010

In this report we present two unrelated patients with the postaxial dysostosis syndrome (Miller syndrome) and document further the phenotypic variability of the craniofacial stigmata and of the postaxial (and preaxial) upper and lower limb reduction anomalies.
Chorionic villi sampling for early prenatal diagnosis: an option for the Jewish orthodox community
Authors: Zakut H. , Zamir R. , Yemini O. , Sindel L. , Kohn G.
Published: July 2010

The Jewish religion permits abortion up to 40 days after conception. To accommodate the Jewish orthodox community, prenatal diagnosis in the eighth gestational week may be a feasible goal with clear benefits. We present our experience with chorionic villus sampling (CVS), wherein out of 144 patients requesting CVS, 125 were found to be suitable for the procedure. Excluding patients with fundal placenta and cervical or uterine myoma, chorionic sampling was successfully performed on 102 out of 106 patients (96.2%) and a chromosome result was available for 98 of those patients (96%). Fetal losses, within 14 days following procedure, were 2 out of 125 (1.6%). No complications were encountered following the procedure. The cytogenetic analysis was improved by culturing CVS fragments for 48 h, after which clearer banding patterns could be observed. One of the CVS preparations, from a 7.2/7‐week‐old embryo was successfully examined. Short‐term (6 days) cultures were used as an additional method for chromosome analysis, to extend and confirm results obtained by the direct method.
Phenotypical features of an unique Irish family with severe autosomal recessive Osteogenesis imperfecta
Authors: Williams E. Mair , Nicholls Alan C. , Daw Sara C. M. , Mitchell Nan , Levin L. Stefan , Green Bryan , MacKenzie Janet , Evans Dewi‐R. , Chudleigh Patricia A. , Pope F. Michael
Published: July 2010

Severe Sillence type II/III Osteogenesis imperfecta (OI) is a lethal or severely crippling disease with either autosomal dominant or recessively inherited type I collagen mutations. Here we describe the detailed clinical features of a thin‐ribbed OI variant with deformed limbs. The three consecutively affected children showed no genetic linkage with either of the two type I collagen genes, which implies that a novel mechanism causes this clinical phenotype. It can be prevented using ultrasound to diagnose affected foetuses.
Variant nucleolus organizing regions and the risk of Down syndrome
Authors: Green Jeffrey E. , Rosenbaum Kenneth N. , Rapoport Stanley I. , Schapiro Mark B. , White Beverly J.
Published: July 2010

In order to determine whether nucleolus organizing region (NOR) heteromorphisms of the acrocentric chromosomes could identify individuals at risk for having offspring with trisomy 21, a comparison was made between 43 parents of individuals with Down syndrome and 39 controls. NORs, as visualized by silver staining, were analyzed by mean number per cell, average size, total NOR “mass” per cell (designated mean score per cell) and by mean number of acrocentric chromosome satellite associations per cell. No “double NOR” variants (dNOR) were found in either the control or study group in contrast to observations of others (Jackson‐Cook et al. 1985). The risk for having a child with trisomy correlated with a higher frequency of associations and number of NORs per cell, but slightly lower average NOR size. Although these group differences were statistically significant, specific types of NOR variants such as enlarged or dNORs were not associated with the risk of having trisomy 21 offspring. The constancy of NOR mass per cell in our control and study groups indicates that NOR activity remains constant, even though distribution of the rRNA genes (variation in number and size of NORs on the 10 acrocentrics) may vary.
Retinitis pigmentosa, hearing loss and vitiligo: report of two patients
Authors: Dereymaeker A. M. , Fryns J. P. , Ars J. , Andresescu J. , van den Berche H.
Published: July 2010

In this report we describe the association of retinitis pigmentosa, hearing loss and vitiligo in two non‐related patients. The second patient developed, in addition, an axonal polyneuritis after the age of 30. Previous reports dealing with this unusual combination of symptoms are discussed.
Linkage in a family with X‐linked Charcot‐Marie‐Tooth disease
Authors: Haites N. , Fairweather N. , Clark C. , Kelly K. F. , Simpson S. , Johnston A. W.
Published: July 2010

The gene for the X‐linked form of Charcot‐Marie‐Tooth disease (CMT Peroneal Muscular Atrophy, X‐linked: McKusick No. 30280) has been shown in a single family to be linked to DXYSI with a lod score of 4.55 at a recombination fraction of 0.03 and to PGK1 with a lod score of 3.34 at zero recombination. This is in agreement with previous work based on several families. Pooled data from this family and 7 previously reported families give a maximum lod score of 12.04 at θmax of 0.05 for linkage between CMTX and DXYS1 loci.
Unique inheritance of streptomycininduced deafness
Authors: Higashi Koichiro
Published: July 2010

Analysis of reported families which include two or more members with streptomycin‐induced hearing loss reveals that the trait of high susceptibility of cochlea to streptomycin is transmitted primarily through females. This is not explained by ordinary Mendelian inheritance; rather it is best understood by extranuclear inheritance.
Chromosome studies and fertility treatment in women with ovarian failure
Authors: Hens L. , Devroey P. , Waesberghe L. Van , Bonduelle M. , Steirteghem A. C. Van , Liebaers I.
Published: July 2010

In vitro fertilization and embryo transfer or gamete (or zygote) intra‐Fallopian transfer after ovum donation were performed in 16 patients with primary or secondary amenorrhea, associated with chromosome abnormalities. The patients showed the wide range of (mostly X) chromosome abnormalities characteristic for women with primary or premature ovarian failure. Four of these patients became pregnant and three of them have delivered healthy infants with a normal karyotype. This pregnancy rate is far superior to the accepted fertility figure in these patients. When these results were compared with the fertility treatment results of three other groups of women with absent ovarian function (1. ovarian dysgenesis; 2. surgical castration; 3. premature menopause) but with a normal 46.XX karyotype, no difference in treatment efficiency could be detected. These results offer a promising approach for the treatment of infertility in agonadal patients with chromosome aberrations.
A genetic epidemiologic investigation of breast cancer in families with bilateral breast cancer. II. Linkage analysis
Authors: Goldstein Ausa M. , Haile Robert W. , Spence M. Anne , Sparkes Robert S. , Paganini‐Hill Annlia
Published: July 2010

We conducted genetic linkage analyses of breast cancer in 20 pedigrees, each having at least one case of bilateral breast cancer diagnosed before 50 years of age. We tested for linkage using inheritance models from previous segregation analyses, incorporating differences in risk based on menopausal status into the analyses. We tested for heterogeneity by predividing the data set based on the interval between diagnoses of the proband's two primaries (less than 1 year (synchronous) versus at least 2 years (asynchronous)), and on the histological types of breast cancer in the pedigrees. Very tight linkage could be excluded between breast cancer and ABO, GC, GPT, MNS, and PGM1 for some of the different linkage analyses. A maximum lod score of +1.01 (at θ=0.001) between ACPI and a breast cancer susceptibility locus was seen in the asynchronous all‐cases subsample.
Osteogenesis imperfecta with congenital joint contractures (Bruck Syndrome)
Authors: Viljoen Denis , Versfeld Gerry , Beighton Peter
Published: July 2010

Five children from three unrelated families were bom with symmetrical contractures of the knees, ankles and feet. An initial diagnosis of arthrogryposis multiplex was made, but frequent fracturing occurred after walking commenced and it was then recognised that the children had osteogenesis imperfecta. The pathogenesis of the congenital contractures is unknown, but the symmetry and lack of evidence of prior fracturing is suggestive of articular immobility during early intra‐uterine development. The consistency of the anatomical distribution of the contractures, in the setting of a uniform 01 phenotype, is suggestive of syndromic identity. A similar case was documented by Alfred Bruck in 1897 and we propose that the eponymous designation “Bruck syndrome” should be applied to the disorder.
Pena‐Shokeir phenotype with major CNS‐malformations: clinicopathological report of two siblings
Authors: Erdl R. , Schmidtke K. , Jakobeit M. , Nerlich A. , Schramm T.
Published: July 2010

Clinical and pathological features of two siblings of opposite sex with the Pena‐Shokeir phenotype are reported. A detailed account of the prenatal and dysmorphological findings is given in one case. A broad range of deformations regarded as secondary to fetal hypokinesia was present, including a number of yet unreported findings. One case showed additional endocrine hyperplasia and left lung trilobation. Both siblings displayed extensive, highly similar CNS‐abnormalities. The type and convergence of these malformations differ from previously reported cases and characterize a new familial subtype of the Pena‐Shokeir phenotype.
Familial steatocystoma multiplex: HLA, Gm, Km genotyping and chromosomal analysis in two unrelated families
Authors: Cuccia‐Belvedere M. , Brazzelli V. , Martinetti M. , Berardesca E. , Dugoujon J. M. , Paoli F. De , Borroni G. , Rabbiosi G.
Published: July 2010

Steatocystoma Multiplex (S.M.) is an inherited condition characterized by the appearance of cysts during the first or second decade of life. Familial cases have occasionally been reported. We studied 13 patients affected by S.M. from two unrelated families, focusing our attention on HLA, Gm and Km genotypes and on chromosomal analyses. Although we failed to correlate the syndrome with a particular HLA, Gm or Km haplotype, we report some peculiarities and differences between these two families and the healthy Italian population.
Application of the anthropometric discriminant functions in estimation of carrier probabilities in Martin‐Bell syndrome
Authors: Loesch Danuta Z. , Scott David
Published: July 2010

A method of estimating the likelihood ratio and the risk of an individual being affected with Martin Bell syndrome (MBS) from anthropometric measurements is described. The procedure is based on the discriminant functions (one for each sex), generated in our previous study in order to separate the individuals with MBS from the normal individuals. The procedure is illustrated by the examples of estimating the likelihood and the likelihood ratio in four individuals of either sex, belonging to MBS families, where the discriminant score value obtained from each individual is compared with the empirical (normalized) distribution of discriminant scores from the known MBS and normal subjects of a corresponding sex. The ways in which the risk of an individual being MBS is estimated in the general population or in members of the MBS families are indicated. The limitations of the discriminant diagnosis based on body measurements, as well as its particular applications in studies of the Martin‐Bell syndrome, are discussed.
Macrosomia, microphthalmia, ± cleft palate and early infant death: a new autosomal recessive syndrome
Authors: Tebi Ahmad S. , Al‐Saleh Qusay A. , Hassoon Mohammed M. , Farag Talaat I. , Al‐Awadi Sadika A.
Published: July 2010

An Arab girl with macrosomia, severe microphthalmia and early infant death is reported. Four other sibs were similarly affected; three of them had median cleft palate. All five sibs showed respiratory infections in early life and died either unexpectedly or because of a documented overwhelming infection. Parental consanguinity and affected sibs of both sexes strongly suggest autosomal recessive inheritance in this apparently new syndrome.
Spondylocostal dysostosis: an example of autosomal dominant transmission in a large family
Authors: Floor E. , Jong R. O. De , Fryns J. P. , Smulders C. , Vles J. S. H.
Published: July 2010

This report gives a description of a three‐generation family in which spondylocostal dysostosis associated with previously unreported neurological complaints occurred in five family members, suggesting autosomal dominant inheritance. A review of the literature is presented and previously unreported neurological complaints, e.g. neurogenic claudicatio, are emphasized.
Fabry's disease
Authors: Hasholt Lis , Wandall Annelise , Sørensen Sven Asger
Published: July 2010

Fifteen hemizygotes and 30 heterozygotes have been diagnosed since our investigations of Fabry's disease were started 10 years ago. They belong mainly to three Danish families. Genetic counseling and prenatal diagnoses have been performed, and in vitro studies of cultured fibroblasts and endothelial cells have been made with special reference to enzyme therapy.
Impact of medical genetics on environmental medicine
Authors: Beckman Lars
Published: July 2010

Medical genetics as a discipline has contributed basic knowledge of great applicability in environmental medicine, e.g. 1) the demonstration that environmental agents may cause chromosomal damage, 2) that chromosome aberrations are correlated with increased risks for cancer and spontaneous abortion, and 3) that the susceptibility to cyto‐ and genotoxic damage may be influenced by genetic factors. This paper discusses examples of applications of genetic knowledge in environmental medicine and areas for future research.
Impact, logistics and prospects of traditional prenatal diagnosis
Authors: Furhmann W.
Published: July 2010

Traditional second trimester prenatal diagnosis (PD)‐by amniocentesis was introduced about 20 years ago. It is still the most frequently used procedure for this purpose. About 85% of all requests for PD are based on maternal age alone. The commonest indication is a maternal age of 35 or higher at delivery. Attempts are being made to improve utilization of the limited laboratory capacity by evaluating the indication for PD by combining age and other indicators, ie. maternal‐serum‐alpha‐fetoprotein and unconjugated estriol. Chorionic villus sampling so far has appealed to an additional group of pregnant women rather than being a replacement for the older procedure. While the impact of PD on the individual woman and her family is great, it has limited impact on the prevalence of Down syndrome patients in the society. Of major concern is the impact of PD on the attitude to a pregnancy with a possibly affected child, on the attitude to induced abortion in general and on the acceptance of disabled individuals. The importance of proper genetic counseling including ethical issues is stressed.
Automated cytogenetic analysis: accomplishments, present status and practical future possibilities
Authors: Lundsteen Claes , Philip John
Published: July 2010

During the past 25 years, much research has been put into the development of systems for automated cytogenetic analysis. Currently more than 10 chromosome analysis systems are commercially available at prices from USD 50000–200000.

The Magiscan chromosome system (Joyce‐Loebl Ltd.) was the first system to be integrated into a clinical cytogenetic laboratory at Rigshospitalet in Copenhagen. From 1983–1987, 6752 cases were analysed with two systems which can do both metaphase finding and karyotyping, and 7036 karyotypes were produced with one “karyotyping‐only” system. The development of automated cytogenetics systems is continuing in order to improve their performance further.
Impact of complex genetic conditions on public health
Authors: Vogel F.
Published: July 2010

Complex genetic diseases are often common; in most common diseases liability is influenced by genetic variation. The ways in which this variation is analyzed are discussed using diabetes, affective disorders and schizophrenia as examples. Molecular biology has opened new paths for a more incisive analysis of genetic heterogeneity and biological mechanisms. However, important population genetic aspects such as mutation and selection are largely unexplored. Therefore, predictions regarding possible increases or decreases in frequencies of susceptibility genes are hardly feasible. In many cases, however, the public health impact of such diseases can be alleviated and the quality of life of the individual can be improved, by appropriate adaptation of relevant environmental factors.
X‐linked myotubular myopathy: clinical and pathological findings in a family
Authors: Oldfors A. , Kyllerman M. , Wahlström J. , Darnfors C. , Henriksson K. G.
Published: July 2010

A five‐generation family with recessively inherited X‐linked myotubular myopathy was investigated. Two of the affected boys, who were siblings and were verified by muscle biopsy to have the disease, died 3 days and 3 months, respectively, after birth. They showed marked hypotonus from birth, general muscle weakness and asphyxia. Three other boys, who were probably affected by the disease, had severe asphyxia and died shortly after birth. In three of the five cases there was polyhydramnios. The muscle biopsies of the two siblings revealed predominance of small fibres with central nuclei and accumulation of mitochondria in the central parts of the fibres. In one of the boys mainly the type 1 fibres were hypotrophic. The postmortem examination revealed variation in the involvement of different muscles, the anterior tibial muscle being the most severely affected. Intrafusal muscle fibres and myocardium were apparently unaffected. There was no involvement of the spinal cord. The clinical examination of two obligate carriers in the family revealed no muscle weakness but the muscle biopsy showed pathological changes including greatly increased variability of fibre size, and many fibres with central nuclei. The findings indicate that muscle biopsy is of value in genetic counselling to detect carriers although the observed changes were unspecific.
Leukocyte and plasma N‐laurylsphingosine deacylase (ceramidase) in Farber disease
Authors: Ben‐Yoseph Y. , Gagné R. , Parvathy M. R. , Mitchell D. A. , Momoi T.
Published: July 2010

Severe deficiency of acid ceramidase activity (4–5% of normal) was demonstrated in cultured skin fibroblasts, leukocytes and plasma from a 1‐year‐old boy who was diagnosed as being affected with Farber disease. Determination of ceramidase activity in plasma was achieved by a highly sensitive assay employing a ceramide substrate containing radiolabeled C12 N‐acyl moiety (N‐lauryl). The enzyme activity in the parents' leukocytes and plasma was found to be reduced to 18–47% of the respective normal values, and that determined in a plasma specimen from a patient with I‐cell disease was about 4 times elevated above the normal level.
An aetiological study of isochromosome‐X Turner's syndrome
Authors: Carothers Andrew D. , Mey Rhona De , Daker Michael , Boyd Elizabeth , Connor Michael , Ellis Patricia M. , Stevenson David
Published: July 2010

In an attempt to resolve conflicting evidence from the literature concerning the existence of a paternal age effect in 46,X,i(Xq) Turner's syndrome, we have analysed data on all known cases ascertained in the main population centres of Scotland and on others ascertained in England, using population controls matched for year of birth. There was a significant (P = 0.02) increase of 2.3 years in the mean paternal age of the Scottish cases, and a smaller and non‐significant increase in their mean maternal age. Logistic regression analysis confirmed that the primary association was with paternal, rather than maternal, age. For the English cases, however, there were small and non‐significant decreases in their mean maternal and paternal ages. The differences between the two groups were also significant, but cannot be explained by any likely source of ascertainment bias. We therefore conclude that there is no evidence for a universal paternal age effect in this condition, but that at least one mechanism of origin, occurring with variable frequency, may be associated with increased paternal age. Using data from this and earlier published studies, we estimate the incidence of individuals with a 46,X,i(Xq) cell line to be between 3.3 and 13 per 105 female livebirths.
Angiokeratoma corporis diffusum in GM1 gangliosidosis, Type 1
Authors: Beratis Nicholas G. , Varvarigou‐Frimas Anastasia , Beratis Stavroula , Sklower Susan L.
Published: July 2010

A patient with severe deficiency of β‐galactosidase, who developed skin lesions of angiokeratoma corporis diffusum between the 3rd and 10th month of life, is described. The activity of other lysosomal enzymes, including α‐neuraminidase, was normal. The first signs of the disease were noticed during the first month of life. By 3 months coarseness of the face and psychomotor retardation were present. In addition to angiokeratoma, he had large mongolian spots and several scattered slate‐blue spots of pigmentation over his body. With the exception of the skin lesions, the other clinical signs and the course of the psychomotor deterioration were within the clinical picture of GM1, gangliosidosis, Type 1.
Holt‐Oram syndrome associated with the hypoplastic left heart syndrome
Authors: Glauser Tracy A. , Zackai Elaine , Weinberg Paul , Clancy Robert
Published: July 2010

We present the first case of Holt‐Oram syndrome associated with the lethal congenital heart defect of hypoplastic left heart syndrome. The possible pathophysiological link is explored and the need for careful genetic and cardiologic evaluation in these patients is reiterated.
A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family
Authors: Boehme D. H. , Shotar Ali Oqleh
Published: July 2010

A sibship is reported of three generations of a Jordanian family of normal intelligence with a complex malformation of upper extremity, shoulder and thorax, which is combined with variously expressed congenital heart disease. The deformity consists of a flat glenoid fossa, a hypoplastic scapula, aplasia of the humerus and/or radius, bony spurs of the elbow joint and in the shoulder region, hypoplasia of the carpal joints and hypodactyly with aplasia of the thumb. The claviculae are short, thick and abnormally curved and there are kyphoscoliosis and pectus excavatum. Four siblings show congenital heart disease. Pelvis and lower extremity are normal. The condition is inherited as a Mendelian autosomal dominant.
An apparently new autosomal recessive syndrome with facial dysmorphism, macrocephaly, myopia and Dandy‐Walker malformation
Authors: Buttiens M. , Fryns J. P. , Berghe H. van den
Published: July 2010

In this report we describe an apparently new MCA‐MR syndrome with Dandy‐Walker malformation in three severely mentally retarded siblings born to normal, non‐consanguineous parents. In addition, they presented macrocephaly, facial dysmorphism, extreme myopia and brachytelephalangy with short and broad finger‐nails.
A new syndrome of familial short stature, small hands, valvular heart disease and a characteristic facies
Authors: Collins F. A. , Partington M. W. , Mulcahy D. , Turner G.
Published: July 2010

A mother and two daughters are presented with severe short stature with disproportionately short limbs, small hands, clinodactyly, valvular heart disease and a distinctive facies with ptosis, high‐arched palate and crowded dentition. This appears to be a previously undescribed syndrome, probably inherited as an autosomal dominant trait.
Metachromatic leukodystrophy in Greece: observations on 4 cases
Authors: Michelakakis Helen , Dimitriou Evagelia , Bartsocas Ch. , Skardoutsou Angeliki , Giouroukos S.
Published: July 2010

We report our findings in four cases of metachromatic leukodystrophy diagnosed in Greece during the last 4 years. The age of onset and the clinical symptoms were those described for the late infantile form of the disease. However, one patient retained his speech and mental abilities despite his pronounced motor regression and neurological involvement. This was combined with high residual arylsulphatase A activity in white blood cell homogenates even in the 0°C incubation assay.
Clinical considerations in Buschke‐Ollendorff syndrome
Authors: Walpole Ian R. , Manners Prudence J.
Published: July 2010

This brief report describes a mother and two daughters with the rare Buschke‐Ollendorff syndrome. That the typical dermal connective tissue naevi lesions may become less obvious with time and that the condition is not always so “benign” are important clinical features not well recognised. Incorrect diagnosis may lead to embarkation upon hazardous management.
The phakomatoses as paracrine growth disorders (paracrinopathies)
Authors: Kousseff Boris G.
Published: July 2010

A microcomputer database management system retrieved all 170 probands with phakomatoses evaluated through the genetic clinics at the University of South Florida between January 2, 1982 and December 31, 1987. Neurofibromatosis (NF) was the diagnosis of 118 of them; 42 had other phakomatoses and 10 had transitional phenotypes difficult to classify. The analysis of the hamartomas of all probands indicated disorganized differentiation and overgrowth of cell species characteristic for the involved tissue and location. Abundance of extracellular fibrillary components was also evident in most hamartomas. Adequate blood suppy was a conditio sine qua non. This was seen in monogenic, sporadic, transitional and combined phakomatoses alike and implied a common pathogenesis. The paracrine growth factors and their regulation emerged as the most plausible common denominator for the pathogenesis. A unitary pathogenetic hypothesis is proposed that the phakomatoses represent paracrine growth regulation disorders (paracrinopathies). Conditions such as fibromatoses, lipomatoses, lipody‐strophies, hemihyper/hypotrophies, including Russell‐Silver and Beckwith‐Wiedemann syndromes may be proven to be paracrinopathies as well.
The common fragile site in band q27 of the human X chromosome is not coincident with the fragile X
Authors: Sutherland Grant R. , Baker Elizabeth
Published: July 2010

The common fragile site on the end of the long arm of the human X chromosome has been shown to be at a different location from the rare fragile site which produces the fragile X syndrome of intellectual handicap. The different locations can be clearly seen in chromosomes at about the 550 band level of resolution. This finding should help resolve difficulties in fragile X cytogenetics where expression of the common fragile site can lead to false positive diagnoses.
Comparison of anatomical location of squamous cell carcinoma within the oral cavity and oropharynx with the incidence of in vitro hyperdiploidy
Authors: Danes B. Shannon , Angelis Paula De , Traganos Frank , Ringborg Ulrik , Nielsen Lars Holme , Melamed Myron R.
Published: July 2010

The anatomical location of the squamous cell carcinoma (SCCA) within the oral cavity and oropharynx influenced the association of SCCA with the biomarker in vitro hyperdiploidy in human dermal fibroblast cultures (IVH). There was a strong association of IVH with the occurrence of SCCA in the anterior 2/3 of the tongue, floor of the mouth and lower alveolar ridge of the oral cavity and in the base of the tongue and pharyngeal wall of the oropharynx. There was a lower association of SCCA with IVH in the tonsillar region of the oropharynx. IVH showed no association with SCCA located in other anatomical parts of the oral region. The patient group whose diagnosis of SCCA in the anterior 2/3 of the tongue occurred prior to the age of 50 years were invariably IVH‐, whereas those diagnosed after the age of 50 years were IVH+, providing evidence for heterogeneity. There was no such correlation of biomarker subgrouping with age of diagnosis demonstrated for SCCA at any other anatomical location within the oral cavity or oropharynx.
X‐linked myotubular myopathy: a linkage study
Authors: Darnfors Catarina , Larsson H. E. Börje , Oldfors Anders , Kyllerman Mårten , Gustavson Karl‐Henrik , Bjursell Gunnar , Wahlström Jan
Published: July 2010

Two families with the congenital X‐linked infantile form of myotubular myopathy have been investigated by linkage analysis using markers from the X‐chromosome. Linkage was found at the locus Xq28 (with DXS52). The analysis gave a peak lod score of 2.41 at the recombination fraction zero. Free recombinations (θ=0.50) were seen using the markers DXS84, DXS14 and DXS146 from the p arm of the X‐chromosome. Since the disorder is very rare, it is important to add cumulative linkage data from the few families that do exist.
Dominant branchial cleft syndrome with characteristics of both branchio‐oto‐renal and branchio‐oculo‐facial syndrome
Authors: Legius E. , Fryns J. P. , Van Den Berghe H.
Published: July 2010

A father and son are described with an autosomal dominant branchial cleft syndrome resembling both the branchio‐oto‐renal and the branchio‐oculo‐facial syndrome. Both syndromes may represent variant expressions of the same autosomal dominant gene.
How necessary is a chromosomal analysis in growth‐retarded girls?
Authors: Eggert P. , Pankau R. , Oldigs H. D.
Published: July 2010

In growth‐retarded girls, shortness may be the only clinical sign of Turner syndrome. Therefore recommendations have been published that a chromosomal analysis should be carried out in every girl showing growth retardation. The present study was carried out to examine whether the head circumference of small girls can serve as a criterion and hence limit the need for expensive chromosomal analysis. The head circumferences of 45 girls with Turner syndrome were compared with those of 41 growth‐retarded girls. It could be shown that the heads of the patients with Turner syndrome had a normal circumference, whereas the heads of the control group were significantly smaller. In view of this result, the risk of overlooking Turner syndrome in diagnosing growth retardation without a chromosomal analysis could be estimated to be 1:9000. The conclusion is drawn that a chromosomal analysis is not necessary in girls whose growth retardation is combined with a small head circumference and who do not show other malformations.
Trisomy 20q. A new case and further phenotypic delineation
Authors: Herens C. , Verloes A. , Laloux F. , Maldergem L. Van
Published: July 2010

The present report concerns the clinical and cytogenetic findings in a liveborn girl with trisomy for the long arm of chromosome 20. She was the unbalanced product of a maternal t(18;20)(q23.2;q13.1) translocation. Our case is compared to the 3 previous reports of trisomy 20q associated with telomeric translocation. Adenosine deaminase dosage falls in the normal range and confirms the exclusion of the ADA locus from the region extending distally to 20q13.1.
Monozygotic twins concordant for Rubinstein‐Taybi syndrome
Authors: Ghanem Qais , Dawod Saleh
Published: July 2010

Monozygotic twin sisters from Qatar, concordant for the Rubinstein‐Taybi syndrome, are described. Skeletal anomalies not previously seen in this syndrome are described. The mode of inheritance is reviewed.
Frequency and effects of the apolipoprotein A‐IV polymorphism
Authors: Visvikis Sophia , Steinmetz Josiane , Boerwinkle Eric , Gueguen René , Galteau Marie‐Madeleine , Siest Gérard
Published: July 2010

Plasma from 158 presumed healthy nuclear families has been analyzed by high‐resolution, two‐dimensional electrophoresis to study the frequency and effects of the genetic polymorphism in human apolipoprotein A‐IV. Two common alleles, apo A‐IV 1 and apo A‐IV 2 were detected with relative frequencies of 0.943 and 0.057, respectively. Autosomal codominant transmission of these two alleles coded for by a single structural locus was demonstrated. Furthermore, we studied the effects of this apo A‐IV variability on total plasma cholesterol, triglyceride, glucose levels and gamma‐glutamyltransferase activity. Statistically significant differences among apo A‐IV genotypes for the average glucose level were detected. The average effect of the apo A‐IV 1 allele was to lower plasma glucose levels by 0.013 mmol/l, whereas the average effect of the apo A‐IV 2 allele was to raise glucose levels by 0.213 mmol/l.
In situ hybridization analysis of isodicentric X‐chromosomes with short arm fusion
Authors: Koch Jørn E. , Kølvraa Steen , Hertz Jens M. , Rasmussen Kirsten , Gregersen Niels , Fly Gerner F. , Bolund Lars A.
Published: July 2010

We present here an alternative approach to the study of mosaic cell lines containing dicentric chromosomes. The approach is based on chromosome‐specific non‐radioactive in situ hybridization with centromere (alpha satellite DNA) probes. The hybridization analysis may be used as an alternative to the C‐band analysis, while at the same time to some extent replacing the Q‐band analysis as well. The advantage of using in situ hybridization is mainly that it allows the very fast screening of a large number of metaphases. We illustrate this new application of the technique by using it for the analysis of two cases of isodicentric X‐chromosomes. The approach is expected to be generally applicable, so that it may be applied to the scoring of other types of chromosomal mosaicism as well.
Intragenic deletions in 164 boys with Duchenne muscular dystrophy (DMD) studied with dystrophin cDNA
Authors: Upadhyaya M. , Smith R. A. , Thomas N. S. T. , Norman A. M. , Harper P. S.
Published: July 2010

DNA from 164 unrelated Duchenne muscular dystrophy patients was screened with cDNA probes from the dystrophin gene. Molecular deletions were demonstrated in 82 (50%) subjects. Sixty‐two deletions (76%) were detected using cDNA probes Cf56a (cDNA 8) and Cf56b (cDNA 6–7) which map to the centre of the gene, while 22 deletions (27%) mapped to the 5′ end of the gene. In three subjects, the deletion extended from the 5′ end to the centre of the gene. One deletion was identified by probe 47–4 (cDNA 5b‐7) alone. In six of the deletions, junction fragments of altered size were observed. Using the three cDNA probes, RW2kb, Cf56a (cDNA 8) and Cf56b (cDNA 6–7), 99% of the deletions were detected. This will have implications for prenatal diagnosis in deletion families. Unlike Becker muscular dystrophy, where the deletions are more homogeneous, the deletions in the present study were heterogeneous both in size and position. No correlation between intelligence and either site or extent of deletion was found.
High urinary excretion of N‐(pyrrole‐2‐carboxyl) glycine in type II hyperprolinemia
Authors: Wajner Moacir , Wannmacher Clóvis M. D. , Purkiss Paul
Published: July 2010

A case report of type II hyperprolinemia in a 5‐year‐old boy and its biochemical investigation is presented. The child has mild developmental delay, recurrent seizures of the grand mal type and EEG alterations. Although this disorder has been recently considered a benign condition, variants accompanied by characteristic symptomatology cannot be fully ruled out. The urinary excretion of high concentrations of N‐(pyrrole‐2‐carboxylic acid)‐glycine conjugate is stressed, since it appears that only one previous report in the literature described this compound in the urine of two patients affected by this disturbance.
Pseudoinflammatory fundus dystrophy: a follow‐up study
Authors: Eriksson Aldur W. , Suvanto Erkki A. , Frants R. R. , Forsius Henrik R.
Published: July 2010

We have performed a reinvestigation of a family with a presumably autosomal recessive form of pseudoinflammatory dystrophy, which we have followed for 25 years. The symptoms in this family are subretinal haemorrhages appearing at age 13–40 years in the central fundus, resulting in glial cicatrication in the outer retinal layers, progressive myopia and profound choroidal atrophy in the advanced stages of the disease. During the follow‐up study, a new affected subject was found in the younger generation, and two collateral cases, who had earlier been considered as probably affected subjects, were now considered to have other fundus affections. The new case is the daughter of an affected female. The possibilities of an autosomal dominant mode of inheritance or pseudodominance are discussed. Extended genealogical studies showed that the parents of all the affected subjects, with the exception of the new case, have their origin in an area which was isolated until recently and have several common ancestors within the last 8–10 generations. Recessive inheritance also logically explains the appearance of the disease in so few other members in the vertical line of the family. To this fundus dystrophy, the rule of Lenz seems to apply: If more or less the same phenotype can be caused by both a recessive and a dominant gene, the phenotype caused by the recessive gene is generally manifested earlier and by more severe symptoms.
Chromosome breakage in lymphocytes from members of cancer families showing autosomal dominant inheritance
Authors: Khouzam M. N. , Tsioupra K. , Delhanty J. D. A.
Published: July 2010

We have conducted investigations on members of three families with increased predisposition to cancer which appears to be inherited as an autosomal dominant trait. The aim of our studies overall is to provide markers for the mutant genes involved, so that gene carriers may be monitored closely for signs of malignant disease. This paper reports on studies of chromosome breakage in lymphocytes from affected and at‐risk family members and control subjects. No increase in spontaneous chromosome breakage was observed in family members compared with controls. An increased sensitivity to chromosome damage induced by the alkylating agent, N‐methyl‐N1‐nitro‐N‐nitrosoguanidine (MNNG), was observed in three members from two families; one person was affected, the others at risk. These families included cases of osteosarcoma, in addition to various types of cancer of epithelial origin. Two members (one affected, one at‐risk) of a third family showed increased sensitivity to the radio‐mimetic agent, bleomycin. This family appeared to represent the cancer family syndrome. Whilst not conclusive at present, our results appear to justify investigation of members of cancer families with respect to sensitivity to chromosome breaking agents.
A male patient with 48,XXYY syndrome: importance of distinction from Klinefelter's syndrome
Authors: Grammatico Paola , Bottoni Ugo , De Sanctis Stefania , Sulli Nicoletta , Tonanzi Tiziano , Onorio Antonio Carlesimo , Del Porto Giuseppe
Published: July 2010

The authors report a patient affected with mental retardation, dysarthria, bilateral testicular hypoplasia and extensive ulcers of the lower limbs. Clinical study and laboratory tests revealed 48,XXYY syndrome. The authors confirm the importance of differential diagnosis from Klinefelter syndrome, illustrating the parameters and the pathology of both syndromes. They discuss the hypotheses concerning the pathogenesis of the ulcerations, and stress the importance of clinical and genetic characterization, leading to a differentiated prognosis of social capacity and prospect of working.
An evaluation of 75 terminations of pregnancy based on abnormal laboratory findings at first trimester CVS
Authors: Leschot N. J. , Kanhai H. H. H. , van Asperen C. J. , Wolf H. , Boer K. , van Prooijen‐Knegt A. C. , Christiaens G. C. M. L. , Verjaal M. , Briet E.
Published: July 2010

Seventy‐five selective terminations, based on abnormal laboratory findings at first‐trimester CVS, were performed in 1581 consecutive pregnancies. In all cases a (semi‐) direct method of cytogenetic analysis was used. The 75 abortions were analysed in number of ways. Confirmatory studies showed that three cases had to be considered as false‐positive findings, and in one other case the results were inconclusive. Based on literature data, it was estimated that 41 of the 75 pregnancies would have resulted in seriously handicapped children, surviving beyond the age of 1 year, if no termination of pregnancy had taken place. Negative side‐effects of the procedure include: spontaneous abortion of chromosomally normal fetuses due to the CVS procedure itself and the need for a number of secondary amniocenteses (5.1%). The advantage of DNA diagnosis in X‐linked diseases is illustrated by comparing the CVS results with a previously published amniocentesis study.
Autosomal dominant osteopetrosis type II with “malignant” presentation: further support for heterogeneity?
Authors: Walpole Ian R. , Nicoll Alan , Goldblatt Jack
Published: July 2010

The osteopetroses are a heterogeneous group of disorders characterised by generalised bony sclerosis. The autosomal dominant form usually has a “benign” prognosis, in contrast to the “malignant” course of the autosomal recessive variety. In this paper we describe a kindred in which the phenotypic spectrum varied from an asymptomatic condition in adults to a severely affected infant, presenting with anaemia, hepatosplenomegaly, hydrocephalus and blindness. The findings in this family are reported and discussed to elucidate further the possible genetic heterogeneity in autosomal dominant osteopetrosis.
Association of hypercholesterolemia and apolipoprotein E4 in school children
Authors: Yanagi Hisako , Shimakura Yae , Yamanouchi Yasuko , Watanabe Yuka , Tsuchiya Shigeru , Hamaguchi Hideo
Published: July 2010

To investigate the association of apolipoprotein (APO) E4 and hypercholesterolemia in children, we studied the APOE phenotypes of 51 school‐age children with hypercholesterolemia and of 51 age, sex and obesity index‐matched controls with normocholesterolemia by two‐dimensional gel electrophoresis. APOE4 was present in 21 of 51 hypercholesterolemic children (41.2%), and in nine of 51 control subjects (17.6%). The difference was significant (p<0.01). This finding indicates that APOE4 is associated with hypercholesterolemia in children.
Phenylalanine hydroxylase gene: silent mutation uncovers evolutionary origin of different alleles
Authors: Dworniczak Bernd , Aulehla‐Scholz Christa , Horst Jürgen
Published: July 2010

Analyzing a panel of 94 phenylketonuria (PKU) alleles for mutations within the phenylalanine hydroxylase (PAH) gene, we identified a G to A transition in exon 7 corresponding to nucleotide 957 in the cDNA sequence. This nucleotide substitution generates a new Alu I site (…GTGGCT…→…GTAGCT…), but does not change the encoded amino acid (GTG245→GTA245= VAL). In our panel of patients the Alu I polymorphism is exclusively associated with haplotypes 4 (mutant or normal alleles) and 3, 16, 17, 28 (normal alleles).
X‐linked myopia: Bornholm Eye Disease
Authors: Schwartz Marianne , Haim Marianne , Skarsholm Dina
Published: July 2010

Linkage analysis in a family with X‐linked myopia gave a positive LOD score (z=4.8 at theta = 0) for linkage to F8C. These results suggest a provisional assignment for the locus of this syndrome to the distal part of the X chromosome at Xq28. Based on the clinical and genetic evidence, a redefinition of this clinical syndrome, named Bornholm Eye Disease (BED), was made to include amblyopia, myopia, and deuteranopia. Facultative signs were optic nerve hypoplasia, reduced electroretinographic flicker function, and non‐specific retinal pigment abnormalities.