bluuebunny/crossref_metadata_2025 huggingface dataset:
Inbreeding and schizophrenia
Authors: Saugstad L. , ØDegård Ø.
Published: July 2010

The unique situation that the Norwegian 1891 census included information on consanguineous relation between spouses and that first admissions to psychiatric hospitals by diagnosis were available for the years 1921‐40, formed the basis for the present study. There are similarities between the pattern of inbreeding and admission rates in our rural communities, but we were unable to demonstrate any significant correlation. This is interpreted as due to selective avoidance in the choice of a marriage partner, particularly between near relatives. Good neighbourhood knowledge was an important factor in our sparsely populated communities with a marriage pattern distinguished by extreme geographical proximity of residence of spouses.

The considerably lower proportion of first cousin matings than expected among parents of psychiatric in‐patients 1926‐55, illustrates the lower psychiatric morbidity in offspring of consanguineous parentage.

Admissions 1921—40 comprised only functional psychoses with a predominance of schizophrenia (> 80%), which today is diagnosed in less than 10%. A decline in incidence rate is not likely, whereas changing diagnostic practice is probably a main factor. The near disappearance of catatonia and hebefrenia could be related to the introduction of psychotropic drugs and the accompanying improvement in hospital treatment. The epidemiology of schizophrenia is unchanged with a significant excess in lower social classes. This could in part be due to schizophrenic phenocopies related to the unchanged social differential in infant mortality and morbidity (including a particular season of birth effect), in part to the prevalence of adverse environment postnatally. The considerably greater male marital differential has probably a social cause, whereas male earlier onset of disease and more severe course of the disease are discussed in relation to the new concept of progressive sexual brain differentiation.
Recombination aneusomy of chromosome 5 associated with multiple severe congenital malformations
Authors: Schroeder H. W. , Forbes S. , Mack L. , Davis S. , Norwood T. H.
Published: July 2010

A male infant is described in whom congenital anomalies were recognized prenatally by ultrasound examination. The infant was delivered following spontaneous labor and died approximately 15 min after birth. An autopsy revealed major anomalies in the central nervous system (holoprosencephaly with premaxillary agenesis), the gastrointestinal system (esophageal atresia) and the heart (tetralogy of Fallot). Chromosomal studies revealed recombinant chromosome 5[46, XY, rec(5), dup q, inv(5)(p15q32)], resulting in partial trisomy 5q and partial monosomy 5p. Cytogenetic investigation of the family revealed a pericentric inversion of chromosome 5 in the father and paternal grandmother,46, XY (and XX, respectively,) inv(5)(p15q32). The congenital anomalies in this infant are more extensive and severe than previously reported in cases of recombination aneusomy involving chromosome 5.
A study into possible deviation from the Hardy‐Weinberg equilibrium by the alleles of the hypervariable sequence in the region of the human insulin gene
Authors: Hubbard A. L. , Clayton J. F.
Published: July 2010

A number of studies have reported on possible relationships between a hypervariable sequence near the 5′ end of the insulin gene and some common diseases. Control populations within these studies appear to disobey the Hardy‐Weinberg equilibrium. In this study we have ascertained the allele frequencies in 181 random individuals. The chi‐squared statistic comparing this population with a theoretical Hardy‐Weinberg population was 0.61. This makes it unlikely that in the general population the Hardy‐Weinberg rule is disobeyed. Possible reasons for the discrepancy between our study and the studies of others are discussed.
The arylsulphatases of chorionic villi: potential problems in the first‐trimester diagnosis of metachromatic leucodystrophy and Maroteaux‐Lamy disease
Authors: Sanguinetti N. , Marsh Jane , Jackson Marie , Fensom A. H. , Warren R. C. , Rodeck C. H.
Published: July 2010

Three pregnancies at risk for late infantile metachromatic leucodystrophy have been monitored using chorionic villus biopsies. In the first of these a false negative diagnosis was made following assay of arylsulphatase A in villi. Subsequent studies have shown that this error was probably due to interference from another sulphatase in the villi, although the possibility that maternal contamination was also partly responsible could not be excluded. For reliable prenatal diagnosis of metachromatic leucodystrophy using chorionic villi it is advisable that studies with the nitrocatechol substrate are carried out on fractionated homogenates, or that the natural substrate is used. Problems may also occur when chorionic villi are used for assay of arylsulphatase B for first trimester diagnosis of Maroteaux‐Lamy disease.
A genetic‐diagnostic survey in an institutionalized population of 173 severely mentally retarded patients
Authors: Fryns J. P. , Kleczkowska A. , Dereymaeker A. , Hoefnagels M. , Heremans G. , Marien J. , Berghe H. VAN DEN
Published: July 2010

In this report we summarize the findings in a genetic‐diagnostic survey of an institutionalized population of 173 severely mentally retarded patients. The etiological study was based on a clinical genetic approach with special attention for dysmorphology and neurological findings. A constitutional disorder, as the direct cause of the severe mental handicap, was found in 75 patients (43.35%). A detailed survey of the different data and findings are given, and compared with the results of previous studies.
Tapeto‐retinal degeneration in four Norwegian counties II
Authors: Gröndahl Jan
Published: July 2010

In four Norwegian counties (fylker) 89 probands with tapeto‐retinal degeneration have been traced and examined by the author. 407 of their nearest relatives (mostly first degree relatives) were also examined. A total of 63 of the relatives were found to be affected, of whom 42 had not been registered previously.

After completion of the examinations the mode of inheritance differed from that previously estimated in 50% of the families.

Of the 48 families with “classical” retinitis pigmentosa, 8% showed autosomal dominant, 50% autosomal recessive and 2% X‐linked recessive inheritance. The remaining 40% were families with solitary cases without consanguinity between the parents of the affected person.

Of five families with retinitis pigmentosa of pericentral type, four demonstrated an autosomal dominant pattern of inheritance.
Calvarial hyperostosis: a benign X‐linked recessive disorder
Authors: Pagon Roberta A. , Beckwith J. Bruce , Ward Byron H.
Published: July 2010

We report a family with what appears to be a unique X‐linked recessive disorder of isolated hyperostosis of the calvarium. Although irregularity of the calvarium and exophytic prominences of the frontoparietal bones were apparent in infancy, premature cranial suture closure did not occur and there was no evidence of increased intracranial pressure despite a Luckenshadel appearance of the skull. Other membranous bones and the tubular bones were not involved. Calvarial bone biopsy from one patient showed vacuolated histiocytes suggesting a storage disease; however, neurologic deterioration, hepatosplenomegaly, and dysostosis multiplex did not occur. The affected family members had normal stature, normal occipitofrontal circumference, and no other medical problems. The biochemical basis of this disorder is not known. Although storage of abnormal material is possible, the long‐term prognosis seems favorable.
Number of loci responsible for the inheritance of high and low activity of paraoxonase
Authors: Nielsen Arne , Eiberg Hans , Mohr Jan
Published: July 2010

On the basis of a Danish family material of Eiberg & Mohr (1981), especially 416 matings with 1595 children where the one parent has high activity of paraoxonase and the other low activity, and the 185 matings with 684 children where both parents have high activity, it is, by consideration of a two‐loci model and other alternatives besides the earlier suggested one‐locus model, confirmed that segregation into high and low activity is largely or exclusively due to a one‐locus system; in case any secondary locus is involved, its most common allele would probably have a frequency above 0.95.
Familial transmission of a non‐Robertsonian translocation dicentric
Authors: Howard P. J. , Berry A. C.
Published: July 2010

A second family showing transmission of a dicentric through three generations involving chromosomes 13 and 18 is presented. Features of non‐Robertsonian dicentric chromosomes are presented and discussed.
Clinical and genetic studies of muscular dystrophy in young girls
Authors: Yoshioka Mieko , Itagaki Yasuko , Saida Kyoko , Nishitani Yutaka
Published: July 2010

During the years 1971‐81, we treated 7 girls with clinical features suggestive of Duchenne dystrophy. Muscle weakness developed at 1.5 or at 5–8 years and progressed rapidly. Two girls were in wheel‐chairs in their teens. Muscle atrophy began in the proximal parts of the lower extremities and pseudohypertrophy of the calf occurred in all patients. Serum creatine phosphokinase (CPK) activity was moderately to highly elevated in all cases and EMG showed a moderate to marked myopathic pattern. Chromosomal studies showed normal finding in the five examined. Mental retardation (IQ 37–73) was present in four. Consanguinity was present in 3 out of the 7 cases. Two mothers showed elevated levels of CPK and myopathic patterns on EMG. In addition, one mother had slight muscle weakness at the age of 42 and another had prominent pseudohypertrophy of the calf. Sex‐linked recessive inheritance might be considered here, because carriers of autosomal recessive type never showed elevated levels of CPK or mild myopathic symptoms. The other five of our seven might be cases of autosomal recessive inheritance, because the mothers had normal serum CPK levels and in 2 families there was a consanguinity.
An infant with thanatophoric dwarfism surviving 169 days
Authors: Stensvold K. , Ek J. , Hovland A. R.
Published: July 2010

A female infant with thanatophoric dwarfism surviving 169 days is described. The genetics of the entity are briefly discussed.
Isolated congenital bowed long bones
Authors: Kapur Saroj , Vloten Ada Van
Published: July 2010

An infant with prenatal bowed long bones is reported. History of bowed leg bones in the mother during her infancy and improvement of the bowed bones in the child and mother support benign nature of the condition and probable A.D. inheritance.
Pierre Robin anomaly with an accessory metacarpal of the index fingers
Authors: Dignan P. St. J. , Martin L. W. , Zenni E. J.
Published: July 2010

A two‐year‐old female with the Pierre Robin anomaly and bilateral index finger malformations is described. Hypertelorism, full cheeks, posteriorly rotated ears with prominent antihelix, short neck, simian creases, bilateral fifth finger clinodactyly, and short toes with hypoplastic small nails were also present. Her mother had a subsequent pregnancy that resulted in the delivery at 26 weeks, of a stillborn female fetus with cleft palate, index finger anomalies and congenital heart disease. These two patients are the first females reported with this group of anomalies. The etiology of this combination of malformations, the Catel‐Manzke syndrome, is unknown.
Thymus deficiency in an infant with a chromosome t(18;22)(q12.2;p11.2)pat rearrangement
Authors: Bowen Peter , Pabst Henry , Berry David , Collins‐Nakai Ruth , Hoo Joe J.
Published: July 2010

The finding of an unbalanced t(18;22)pat chromosome rearrangement in a boy with multiple anomalies including apparent absence of the thymus is described. The observation is of interest because of the reported association of chromosome 22 rearrangements with the DiGeorge sequence. In contrast to previous reports of this association, the deletion involving chromosome 22 is confined to the short arm.
Congenital heart disease in supernumerary der(22), t(11;22) syndrome
Authors: Lin Angela E. , Bernar Juan , Chin Alvin J. , Sparkes Robert S. , Emanuel Beverly S. , Zackai Elaine H.
Published: July 2010

Congenital heart disease occurred in 62% of the reported cases of supernumerary der(22) syndrome. These were most commonly acyanotic lesions such as atrial septal defect, ventricular septal defect or patent ductus arteriosus. Heart disease did not, however, appear to be a major determinant of survival.
Deleted ring chromosome 22 in a mentally retarded boy
Authors: Gustavson K.‐H. , Arancibia W. , Eriksson U. , Svennerholm L.
Published: July 2010

A mentally retarded boy with a ring chromosome 22, where most of band q13 was deleted, is reported. The fact that the leucocyte β‐galactosidase and a‐galactosidase B activities were normal, but the arylsulphatase A activity only half of the normal is consistent with a gene dosage effect and that the arylsulphatase A locus is located more distally, than the gene loci for the other two enzymes, in the deleted part of 22q13.
Dominantly inherited craniodiaphyseal dysplasia: A new craniotubular dysplasia
Authors: Schaefer B. , Stein S. , Oshman D. , Rennert O. , Thurnau G. , Wall J. , Bodensteiner J. , Brown O.
Published: July 2010

We describe a mother and her male infant affected with a craniotubular dysplasia characterized by severe craniofacial hyperostosis and sclerosis with obliteration of paranasal sinuses and foramina of the skull base. Subsequent severe bilateral hearing loss and facial diplegia with relative sparing of the optic nerves were noted. The long bones show extreme asymmetric hyperostosis and sclerosis of the diaphyses and evidence of a modelling defect in the metaphyses. The spine, ribs, clavicles, and pelvis all show some degree of sclerosis and defective modelling, but are less severely involved. According to the definition by Gorlin, this disorder would best be classified as craniodiaphyseal dysplasia. Distinguishing features in these two patients as contrasted to previously described cases include a greater degree of hyperostosis and sclerosis than that described for other patients with craniodiaphyseal dysplasia, apparent dominant transmission, and significant metaphyseal involvement.
A postaxial Polydactyly and progressive myopia syndrome of autosomal dominant origin
Authors: Czeizel A. , Brooser G.
Published: July 2010

A new “postaxial polydactyly‐progressive myopia” syndrome of autosomal dominant inheritance is delineated on the basis of nine affected persons in four generations of one family.
Ring 21 chromosome: the mild end of the phenotypic spectrum
Authors: Gardner R. J. M. , Monk N. A. , Clarkson J. E. , Allen G. J.
Published: July 2010

The case is reported of a child with the karyotype 46, XY, r(21), who presented with linear growth retardation but who appears, at age 2 years 8 months, to be developing normally mentally. There is a small number of reports of mildly affected cases of r(21), and of some with an apparently completely normal phenotype. We presume a structural and functional cytogenetic heterogeneity underlies the observed phenotypic heterogeneity in the ring 21 spectrum.
Neurodevelopmental and psychological aspects in a child with 49XYYYY karyotype
Authors: Sirota L. , Shaghapour S. E. , Elitzur A. , Sirota P.
Published: July 2010

Neurodevelopmental and psychological aspects in a child with 49XYYYY karotype are described. The developmental examination revealed mild mental retardation (I.Q. = 50), disturbances in gross and fine motor development and speech disorders. The child was treated by developmental therapy which improved his abilities for a better social adjustment.
An evaluation of maternal cell contamination in cultures of chorionic villi for the prenatal diagnosis of chromosome abnormalities
Authors: Cooke Heather M. G. , Penketh Richard J. A. , Delhanty Joy D. A.
Published: July 2010

Culture of chorionic villus cells provides a method of obtaining chromosomes of excellent quality for first trimester prenatal diagnosis. Concern exists that maternal cells present in the biopsy may contaminate the culture and lead to misdiagnosis. This study has confirmed that karyotypes obtained from female villus cultures were non‐maternal by establishing the presence of paternal markers using Q‐ and C‐banding. Male cultures were harvested serially to investigate the possibility of maternal cell overgrowth. Of 82 successful cultures investigated, 37 were male and 45 female and of the males 4 contained a mixture of male and female cells. Thorough dissection of the material is essential if maternal cell contamination is to be mininimised. The use of heteromorphic chromosome markers to establish that fetal cells have grown provides valuable reassurance.
DNA polymorphism at the apolipoprotein B locus is associated with lipoprotein level
Authors: Berg Kåre
Published: July 2010

A strong association has been uncovered between DNA variation at the apolipoprotein B (apoB) locus (detectable with the restriction endonuclease Xbal) and apoB level. The findings are suggestive of associations also between this DNA polymorphism and total cholesterol as well as fasting triglyceride levels, confirming recent results reported by British workers. The data suggest that lipid/apolipoprotein associations with the Xbal polymorphism are primarily caused by an effect on apoB level.

In the present and in a previously reported study we found a strong association between the Xbal polymorphism and the homospecific Ag antigenic variation in low density lipoprotein (LDL) which had previously exhibited associations with lipid levels. The present data indicate that the apoB/lipid associations of the Ag and Xbal polymorphisms may reflect the same phenomenon.

The associations reported could reflect variation in an apoB domain close to Ag as well as to the Xbal restriction site that is of importance for lipid binding by apoB. Alternatively, the association of apoB level with the Xbal polymorphism (which reflects a silent third base mutation in a threonine codon) could reflect phenomena related to codon usage.
Genetic heterogeneity in X‐linked agammaglobulinemia complicates carrier detection and prenatal diagnosis
Authors: Mensink E. J. B. M. , Thompson A. , Schot J. D. L. , Kraakman M. E. M. , Sandkuyl L. A. , Schuurman R. K. B.
Published: July 2010

X‐linked agammaglobulinemia (XLA) is a severe antibody deficiency disease reflecting an arrest of B lymphocyte differentiation at the level of precursor B cells. The disease is inherited in an X‐linked recessive mode. In a single eight‐generation pedigree the XLA gene was mapped to the Xq21.3‐Xq22 area of the X chromosome. The data establish close linkage of the XLA locus to the DXS17 restriction fragment length polymorphic (RFLP) marker locus (the lodscore exceeding 6 at = 0). A series of RFLP markers around the DXS17 locus provided an RFLP haplotype of use in genetic counselling within this pedigree. In one other pedigree a phenotypically identical disease was inherited but was accompanied by a high frequency of recombination with the DXS17 locus, which made localisation of the gene at the DXS17 locus highly unlikely (lod score < –3). This genetic heterogeneity complicates genetic counselling within particular pedigrees, especially when the localization of the XLA gene involved in those pedigrees has not been established.
Mental retardation in a patient with Maroteaux‐Lamy
Authors: Vestermark S. , Tønnesen T. , Andersen M. Schultz , Güttler F.
Published: July 2010

An 8‐year‐old boy with Hurler‐like traits including severe mental retardation excreted in his urine a pathognomonic amount of dermatan sulfate. Less than 10% residual activity of arylsulfatase B was found in his leucocytes and fibroblasts. Hurler fibroblasts corrected an abnormally high “SCVincorporation into acid mucopolysaccharides (MPS) in cultured fibroblasts, whereas Maroteaux‐Lamy fibroblasts did not. The patient thus has a rare combination of Maroteaux‐Lamy and severe mental retardation.
Cardiovascular complications in the Ehlers‐Danlos syndrome with minimal external findings
Authors: Shohet I. , Rosenbaum I. , Frand M. , Duksin D. , Engelberg S. , Goodman R. M.
Published: July 2010

Ehlers‐Danlos syndrome (EDS) is clinically and genetically a heterogeneous disorder of connective tissue. Eleven different types of EDS have been documented, several of which have major cardiovascular complications as part of their clinical manifestations. The purpose of this report is to call attention to a form of EDS with minimal external features but severe internal vascular complications.
Cerebellar ataxia and total albinism
Authors: Bamezai R. , Husajn S. A. , Misra S. , Thacker A. K.
Published: July 2010

In this report a family is described where cerebellar ataxia occurred along with total albinism. A possibility of syntenic condition of the two genes responsible for the traits could explain the occurrence of the two conditions. The presence of two traits singly in the sibs reflects a recombinant event and suggests that the linkage is not absolute. Chromosomal study did not show any structural or numerical anomalies except in 1/30 metaphase plates scored in the proband (with cerebellar ataxia) where in chromosome No. 14 proximal intense band (21) seemed to be shifted, inv. (14) (q13q23?). The affected sibs with ataxia and albinism or ataxia alone depicted relatively a lower sister chromatid exchange (SCE) rate than their parents and age matched controls.
Estimation of prognosis and prevalence of retinitis pigmentosa and Usher syndrome in Norway
Authors: GRøNDAHL J.
Published: July 2010

Retinitis pigmentosa was diagnosed in 101 persons from 53 families. The prognosis for visual function was most favourable for the autosomal dominant group (38 patients from 8 families). The autosomal recessive group (40 patients from 25 families) and the 19 solitary cases were very heterogeneous, with prognosis ranging from favourable to very bad. There was a higher intrafamiliar correlation in the autosomal recessive than in the autosomal dominant group. In 28 patients from 18 families with Usher syndrome, almost all had good visual function until 30 years of age, and few had useful visual function after the age of 50. The age when the patients were registered varied between the different genetic types of retinitis pigmentosa, reflecting differences in prognosis. Therefore, ascertainment probability and prevalence were calculated for each genetic group separately. The prevalence of retinitis pigmentosa in Norway, all genetic groups included, was calculated to be 1/4440, the autosomal dominant type of the disease being the most frequent. The prevalence of Usher syndrome was calculated to be 3.6/ 100000. Both retinitis pigmentosa and Usher syndrome were more prevalent in Laps.
How do carriers of hemophilia experience prenatal diagnosis by fetal blood s ampling?
Authors: Ljung R. , Tedgård U. , McNeil T. , Tedgård E.
Published: July 2010

A semistructured personal interview was performed with 29 carriers of hemophilia A or B, 1–4 years after a pregnancy in which prenatal diagnosis (PND) of hemophilia was performed by fetal blood sampling. The carriers had received different recommendations regarding future pregnancies, and 14/29 did not know before they became pregnant that PND by fetal blood sampling was possible. One third of the women felt that important information was lacking in the consultations that preceded the PND.

The conclusions regarding future genetic counselling are that more attention should be paid to improving education of all female carriers before a pregnancy, to motivating fathers‐to‐be to attend counselling sessions with the carriers, and to emphasizing the importance of the emotional support given by the family doctor and by other females who have experienced PND.
Syndrome of microcephaly, deafness/ malformed ears, mental retardation and peculiar facies in a mother and son
Authors: Kawashima H. , Tsuji N.
Published: July 2010

We report a mother and son who have a microcephaly with a characteristic dysmorphic face. Prominent manifestations include facial asymmetry, prominent glabella, deafness, low‐set, cup‐shaped ears, thick, protruding lower lip, micrognathia, and mental retardation.

We conclude that these patients have a previously undescribed type of genetic microcephaly. The mother has become normocephalic and we would not have been able to diagnose her condition without her childhood photographs. Such photographs are essential in the recognition of familial syndromes.
Fragile sites are unrelated to reciprocal translocation breakpoints
Authors: Davis J. R. , Hagaman R. M.
Published: July 2010

In 492 cases of reciprocal translocations in balanced carriers, the 984 breakpoints were studied for a possible relationship to the 45 fragile sites. Random coincidence was predicted at 14% and the observed coincidence was 14.3%, indicating that the two events are unrelated. However, chromosomes 1,11 and 14 were exceptions and did show a statistically significant relationship.
The Angelman (Happy Puppet) syndrome: is it autosomal recessive?
Authors: Baraitser M. , Patton M. , Lam S. T. S. , Brett E. M. , Wilson J.
Published: July 2010

We report seven cases of Angelman's syndrome from three families. Recurrence risks are not small, as previously suggested.
Single maxillary central incisor and coloboma in hypomelanosis of Ko
Authors: Bartholomew D. W. , Jabs E. W. , Levin L. S. , Ribovich R.
Published: July 2010

Incontinentia Pigmenti Achromians is a neurocutaneous disorder of uncertain etiology that has been associated with other systemic manifestations including ophthalmologic, musculoskeletal, neurologic and dental abnormalities. Chromosome abnormalities have been documented in some cases but may be coincidental.

We describe a 16‐month‐old black female with an iris coloboma and single central deciduous maxillary incisor in addition to the hypopigmented skin lesions of hypomelanosis of Ito. The combination has not been previously described.
A patient with onychotrichodysplasia, neutropenia and normal intelligence
Authors: Verhage J. , Habbema L. , Vrensen G. F. J. M. , Roord J. J. , Bleeker‐Wagemakers E. M.
Published: July 2010

A 9‐year‐old boy with onychotrichodysplasia and chronic neutropenia is presented. In contrast to cases described earlier, our patient has normal intelligence. The typical features of trichorrhexis nodosa are shown by electronmicroscopic photography. The chronic neutropenia is discussed and supposed to be part of the so‐called lazy leucocyte syndrome.
Centric fission, centromere‐telomere fusion and isochromosome formation: a possible origin of a de novo 12p trisomy
Authors: Rivera H. , García‐Esquivel L. , Jiménez‐Sáinz M. , Vaca G. , Ibarra B. , Cantú J. M.
Published: July 2010

A 5‐month‐old girl had a typical 12p trisomy syndrome due to a monocentric i(12p) present in a 46‐chromosome complement that also included the translocation of all 12q onto the 8p telomere; i.e., her complex karyotype could be written as 46.XX, – 8,–12,+ der(8),t(8;12)(p23.3;cen), + i(12p). The present concurrence of a whole‐arm q translocation and an i(p) for a single chromocome, along with six previous similar instances involving chromosomes 4, 5 and 9, suggests the following origin for such a special rearrangement: a centric fission in Gl initially yielding two telocentrics; at the next replication, the tel(q) translocates onto a nonhomologous telomere (centromere‐telomere fusion), whereas the tel(p) becomes an i(p). This mechanism can be either meiotic or postzygotic and surmises that the translocated long arm retains a partial centromere, which subsequently is inactivated and loses its staining properties.
Deletion of the short arm of chromosome 20
Authors: VIANNA‐MORGANTE A. M. , RICHIERI‐COSTA A. , ROSENBERG C.
Published: July 2010

A de novo deletion of the short arm of chromosome 20 ‐ del (20) (pi 1) or (pllp13) ‐ is described in a child with psychomotor retardation and multiple congenital anomalies.
Distal symphalangism with involvement of the thumbs and great toes
Authors: Matthews S. , Farnish S. , Young I. D.
Published: July 2010

A family is presented in which five individuals in four generations have shown variable expression of distal symphalangism in hands and feet. The mode of inheritance is autosomal dominant. Two individuals show involvement of the thumbs and halluces; this has not been noted previously in true distal symphalangism.
Isolated autosomal recessive renal magnesium loss in two sisters
Authors: Geven W. B. , Monnens L. A. H. , Willems J. L. , Buijs W. , Hamel C. J.
Published: July 2010

A familial autosomal recessive form of isolated renal magnesium loss is presented. Two children in this family suffered from convulsions unrelated to hypomagnesemia. Magnesium infusion studies revealed a lowered threshold but a normal tubular maximum for magnesium. In contrast to two families with the autosomal dominant form of isolated renal magnesium wasting, the calcium excretion in the urine was normal.
Gamma‐glutamyl transferase activity in the amniotic fluid of fetuses with chromosomal aberrations and inborn errors of metabolism
Authors: Macek M. , Annerén G. , Gustavson K. H. , Held K. , Tomášová H. , Hronková J. , Burjanková J. , Hrycejová I.
Published: July 2010

The activity of gamma‐glutamyl transferase (GGT) was measured in amniotic fluid collected between the 16th and 30th weeks of gestation from 81 pregnancies with fetuses affected by chromosomal aberrations, nine with different types of inborn errors of metabolism, two with hemophilia A and one with fragile X syndrome. The GGT activity was compared with that from 1000 normal pregnancies and deliveries resulting in healthy newborns. Contamination of amniotic fluid by blood did not affect the GGT activity. Pathologically decreased activity was found in 25 of 56 amniotic samples from pregnancies with fetal autosomal chromosomal aberrations (44.6%). It was decreased in 15 of 35 pregnancies with fetal trisomy 21 (43%), in 11 of 19 pregnancies with fetal trisomy 18 (58%), in one of three pregnancies with fetal trisomy 13 and in two pregnancies with fetal trisomy 8 and triploidy, respectively. In only three of 16 pregnancies with fetal sex chromosomal aberrations was the GGT activity low. Increased GGT activity was found in three of six pregnancies with unbalanced structurally rearranged karyotypes of the fetuses. Normal GGT activity was observed in all nine amniotic fluid samples from pregnancies with fetuses affected with different forms of inborn errors of metabolism diseases, in the two pregnancies with hemophilia A and in the pregnancy with a male fetus with fragile X syndrome. These and earlier findings indicate that the GGT activity in amniotic fluid is mostly decreased in pregnancies with severe fetal developmental abnormalities, such as autosomal chromosomal aberrations, which could possibly be secondary to an alteration of the microvillar transport system of GGT to the amniotic fluid. GGT testing could thus be a valuable screening method for routine use in prenatal diagnosis of second‐trimester pregnancy.
A rapid and efficient screening method for DNA restriction fragment length polymorphisms
Authors: Boehm Thomas L. J. , Werle Andreas , Drahovsky Dusan
Published: July 2010

Genomic loci displaying DNA sequence polymorphisms represent useful landmarks on the genetic linkage map. We describe an integrated experimental approach to facilitate the detection of DNA restriction fragment length polymorphisms (RFLP) with useful allelic frequencies at loci covered by cloned DNA sequences. The essential feature of the screening method presented is the pooling of DNA from unrelated individuals for Southern blot hybridization analyses using non‐repetitive DNA sequences identified in and preparatively isolated from genomic X phage clones. This procedure results in the detection of RFLP with maximal values of hetero‐zygosity while counterselecting for RFLP with unfavourable allelic frequencies. The described experimental protocol should therefore facilitate the identification and characterization of polymorphic loci with frequent heterozygosity.
Introduction of genomic diagnosis of classical phenylketonuria to the health care system of the German Democratic Republic
Authors: Riess O. , Michel A. , Speer A. , Cobet G. , Coutelle Ch.
Published: July 2010

The phenylketonuria (PKU) dispensary of the Children's Hospital of the Charite, Berlin, GDR, cares for about 140 affected families, representing about one‐third of all PKU families in the GDR. Of these families, 15 expressed their desire for an additional child given the availability of a reasonably reliable prenatal diagnosis procedure. They were investigated by linked RFLP analysis applying a phenylalanine‐hydroxylase‐cDNA probe. Full genetic predictability for prospective fetuses could be obtained for all of them. In eight cases this was possible by the use of one restriction enzyme, and in the remaining seven by a combination of the information from two restriction‐enzyme patterns. No recombination between linked RFLP and the PKU phenotype could be observed in 40 meioses from the investigation of eight families with two affected children each.
Difficulties encountered in a randomization trial of CVS versus amniocentesis for prenatal diagnosis
Authors: Muggah Henry , Hunter Alasdair G. W. , Ivey Brian , Cox David M.
Published: July 2010

In April 1985, having completed a study of the short‐term complications of chorionic villus sampling (CVS), we began a randomized comparison of CVS versus amniocentesis. Our study continued over a 15‐month period, and during that time we had difficulty recruiting patients, with only 10.6% of 1254 women referred for prenatal diagnosis fully participating in this study. However, 30.2% of those eligible by dates and indication chose to enter the study. CVS was available in our province only through this study, and the two most common reasons for such a low rate of recruitment were reporting too late in pregnancy and the concern about the potential risks of CVS. Patients continued to seek counselling too late for CVS despite direct and continuous contact with regional physicians. Our patients' concern about risk might well vary with the attitude of their physicians towards CVS, and with the information provided at the time of pre‐test counselling.

The small number of patients actually enrolled did not permit any meaningful comparison of amniocentesis to CVS. However, our experience with pregnancies lost post‐CVS suggests that a pregnancy with an apparent low implantation at the time of sampling may be at a higher risk of loss.
An aminopterin‐like syndrome without aminopterin (ASSAS)
Authors: Fraser F. C. , Anderson R. A. , Mulvihill J. I. , Preus M.
Published: July 2010

In two patients that closely resembled the phenotype of the syndrome produced by aminopterin in early pregnancy, no evidence of maternal exposure could be elicited. These, plus two similar cases from the literature, suggest the existence of an “aminopterin‐like syndrome sine aminopterin” (ASSA) syndrome. Characteristic traits are: ossification defects of the cranium, temporal recession of hairline with upswept frontal hair pattern, ocular hypertelorism, prominent nose root, low set posteriorly rotated ears, limited elbow movement, variable digital defects, simian creases, short stature, and mild to moderate psychomotor retardation. Autoso‐mal recessive inheritance is a possibility.
Trisomy of the short arm of chromosome 5: autopsy data in a malformed newborn with inv dup (5)(p13.1 → p15.3)
Authors: Kleczkowska A. , Fryns J. P. , Moerman Ph. , Vandenberghe K. , Berghe H. Van den
Published: July 2010

In this paper we report detailed autopsy data of a malformed male newborn with Sp trisomy due to a de novo inverted 5p duplication, inv dup (5Xpl3.1→ pl5.3), and we compare these data with the findings in previous reports on 5p trisomy. Cerebral malformations, i.e. agenesis of corpus caliosum, and Dandy‐Walker cyst malformations, seem to be another characteristic finding in this partial autosomal duplication syndrome.
Microcephalic osteodysplastic dwarfism (Type ll‐like) in siblings
Authors: Verloes Alain , Lambrechts Lucien , Senterre Jacques , Lambotte Claude
Published: July 2010

We report about two sibs showing a common pattern of birth defects, with a pedigree suggestive of autosomal recessive heredity. The main fcatures are intrauterine growth failure with very low birthweight; disproportionate dwarfism with predominantly distal shortening of limbs; small cubitally inclined clenched hands; microcephaly with Seckel‐like faciès and delayed psychomotor development. X‐ray findings include metaphysal flare, V‐shaped femoral meta‐physes and bowing of forearms. Primordial microcephalic osteodysplastic dwarfism Type II is discussed. Metabolic and nutritional data are presented and discussed.
X‐linked myotubular myopathy: intrafamilial variability and normal muscle biopsy in a heterozygous female
Authors: Keppen Laura Davis , Husain Muhammad M. , Woody Robert C.
Published: July 2010

The myotubular myopathies are a heterogeneous group of muscle disorders in which x‐linked, autosomal recessive, and autosomal dominant inheritance hâve been reported. Female carriers of x‐linked myotubular myopathy have been reported to have abnormal muscle biopsies. We report a woman who had a normal muscle biopsy but who had 2 sons with myotubular myopathy by different fathers, indicating that a normal muscle biopsy of the mother cannot exclude x‐linked inheritance. The quantity of fetal activity correlated with the severity of the disorder in this pedigree.
Heterogeneity of pseudoxanthoma elasticum: delineation of a new form?
Authors: Viljoen D. L. , Pope F. M. , Beighton P.
Published: July 2010

Sixty‐four patients with pseudoxanthoma elasticum (PXE) were investigated in a nationwide study within South Africa and Zimbabwe. Thirty‐nine individuals formed a distinct clinical subgroup. Thèse persons were found exclusively among people of Afrikaner descent, whose origins are mainly derived from Dutch and French‐Huguenot stock. This disorder was inherited as an autosomal recessive trait and presented mild to moderate cutaneous and cardiovascular manifestations. However, after the third decade of life severe visual impairment developed and culminated in blindness in 8 people by the age of 50. The cause of the visual defect was progressive extension of angioid streaks into the macula with neovascularization and haemor‐rhage. Laser therapy may have prevented further bleeding in 4 instances. The severity of ocular involvcment contrasted with the mildness of the skin changes, and in this respect the condition seems to differ from previously delineated autosomal recessive forms of PXE.
Effect of combinations of antioxidants on oxygen radical‐induced sister chromatid exchanges
Authors: Weitberg Alan B.
Published: July 2010

Oxygen radical scavengers significantly reduced the number of sister chromatid exchanges in Chinese hamster ovary cells exposed to an oxygen radical‐generating enzyme System. When vitamin E was combined with these antioxidants, no genetic toxicity was observed.
Suggestion of linkage of a major locus for nonsyndromic orofacial cleft with F13A and tentative assignment to chromosome 6
Authors: Eiberg H. , Bixler D. , Nielsen L. S. , Conneally P. M. , Mohr J.
Published: July 2010

A Danish material of 58 pedigrees with nonsyndromic orofacial cleft, selected out of a compre‐hensive Danish material for suggestiveness of autosomal dominant inheritance, was studied for linkage with 42 non‐DNA polymorphic marker Systems. Both cleft lip with or without cleft palate (CL(P)) and cleft lip alone (CP) were, for the purpose of linkage analysis, scored as if they were due to an autosomal dominant gène with complete penetrance. The highest lod score was with the blood clotting factor XIIIA (F 13A): for maies alone z=3.40 at theta = 0.00, for females alone z=0.30 at theta=0.21, and for these together z = 3.66 at theta=0.00 for males and 0.26 for females. Since F13A is known to be located distally on chromosome 6, we tentatively assign a major locus for orofacial cleft to this region. Since both CL(P) and CP pedigrees contribute to the positive score, the question arises whether this locus carries two cleft alleles.
Familial absence of the trapezius muscle with associated shoulder girdle abnormalities
Authors: Gross‐Kieselstein E. , Shalev R. S.
Published: July 2010

Two brothers with congenital absence of the trapezius, pectoralis, supraspinatus and serratus anterior are reported and the relevant literature reviewed.
Clinical anophthalmos in a family
Authors: Sensi A. , Incorvaia C. , Sebastiani A. , Calzolari E.
Published: July 2010

Monolateral or bilateral anophthalmos recurring in the absence of other associated defects in six members of a family is reported. The malformation appears to be inherited as a dominant (autosomal or X‐linked) trait with incomplete penetrance. Implications for genetic counselling are briefly discussed.
Monosomy and trisomy of 15q24→qter in a family with a translocation t(6;15)(P25;q24)
Authors: Kristoffersson Ulf , Heim Sverre , Mandahl Nils , Sundkvist Lennart , Szelest Jan , Hägerstrand Inga
Published: July 2010

A child with multiple anomalies, including growth retardation, a left‐sided diaphragmatic hernia with lung hypoplasia, and cerebral malformations is described. Cytogenetic investigation demonstrated a deletion of the distal part of one chromosome 15, del(15)(q24qter), an aberration not previously described. Family studies revealed that the mother had a balanced translocation, t(6;15)(p25;q24). Two of her subsequent pregnancies resulted in abortions after prenatal diagnosis: one fetus was trisomic for 15q24→qter, while the other had monosomy 15q24→qter and a left‐sided diaphragmatic hernia similar to the first child.
Evidence for a sperm mutation resulting in Duchenne muscular dystrophy
Authors: Børresen A. L. , Heiberg A. , Møller P. , Berg K.
Published: July 2010

DNA analysis of Xp21 markers in a family with two brothers affected with Duchenne muscular dystrophy (DMD) revealed that the mutation most likely had occurred in a grandpaternal sperm. There is therefore a low risk that the maternal aunts and their daughters are carriers of the DMD gene.
X‐linked retinoschisis is closely linked to DXS41 and DXS16 but not DXS85
Authors: Alitalo Tiina , Kärnä Jussi , Forsius Henjik , de la Chapelle Albert
Published: July 2010

A linkage study was carried out in nine families with 24 males affected by X‐linked recessive retinoschisis (RS), using three polymorphic DNA probes from the distal segment of Xp. Close linkage of the disease locus with markers DXS41 (probe p99–6) and DXS16 (pXUT23) was found, confirming the location of the RS gene on the distal short arm of the X chromosome. Lod scores for linkage with DXS85 (probe 782) were negative.
Ehlers‐Danlos syndrome: yet another type?
Authors: Viljoen Denis , Goldblatt Jack , Thompson Dave , Beighton Peter
Published: July 2010

A mother and her four children had gross generalized joint laxity, with multiple dislocations and subluxations, moderate skin hyperextensibility and mild connective tissue fragility. Their condition could be categorized in the Ehlers‐Danlos syndrome Type III or the familial undiffer‐entiated hypermobility group of disorders, but differed from these conditions by virtue of the severity of articular complications and the presence of wormian bones in the skulls. We consider that these patients have an undelineated connective tissue disorder; attempts at characterization at the molecular level are underway.
Postaxial polydactyly in association with neurofibromatosis
Authors: Merlob Paul , Levy Yizhak , Shuper Avinoam
Published: July 2010

Von Recklinghausen neurofibromatosis may present many skeletal abnormalities as common features. We describe a family with postaxial polydactyly and neurofibromatosis, an association which has not been previously reported. The special characteristics of postaxial polydactyly of this family were its bilateral and symmetrical appearance, its limitation only to males, simultaneous presence of types A and B in the same patient, and its occurrence in both hands and feet. Postaxial polydactyly type A appeared only in the affected neurofibromatotic members of this family.
Unstable translocation t(14;21) in a man, inherited as a t(13;14) in one of his daughters
Authors: Siffroi J. P. , Viguie F. , Romani F.
Published: July 2010

The transmission of a Robertsonian translocation was studied in a family after diagnosis of a t rob. (13;14) in a foetus, in the course of a prenatal diagnosis for maternal age. The father was found to be a carrier of a balanced t rob.(14;21) in mosaicism with a normal karyotype. The t rob(14;21) was inherited from the paternal grandfather. A second prenatal diagnosis, 1 year later, revealed a girl with the paternal t rob(14;21). Mitotic and germinal instability of the paternal t rob.(14;21) is discussed, with relation to the long period of drug addiction.
Linkage studies of Best's macular dystrophy
Authors: Yoder Freda E. , Cross Harold E. , Chase Gary A. , Fine Stuart L. , Freidhoff Linda , Machan Carol H. , Bias Wilma B.
Published: July 2010

Genetic linkage studies are presented for nine kindreds with Best's vitelliform macular dystrophy (BVMD). This condition is an autosomal dominant macular dystrophy with reduced penetrance and highly variable expressivity. Asymptomatic carriers were identified with electrooculography, fundus photographs and fluorescein angiography. Blood and saliva specimens were obtained from informative family members and genotyped for 26 polymorphic genetic traits. No firm evidence was found for linkage between BVMD and 18 informative markers; the highest positive lod score was z=0.57 for GPT1 at a recombination fraction of θ=0.30. An atypical form of vitelliform macular dystrophy (VMD‐1) is linked to GPT1 (θ<0.05) and is provisionally assigned to chromosome 16pter‐p11. Our data are not sufficient to rule out loose linkage for GPT1 and BVMD. Thus we were not able to determine whether BVMD and VMD‐1 are allelic mutations or separate genetic disorders. Additional linkage and gene mapping studies of these loci and BVMD (as well as other atypical forms of macular dystrophy) would be useful to further delineate these disorders.
X/Y translocation in a family with X‐linked ichthyosis, chondrodysplasia punctata, and mental retardation: DNA analysis reveals deletion of the steroid sulphatase gene and translocation of its Y pseudogene
Authors: Ballabio A. , Parenti G. , Carrozzo R. , Coppa G. , Felici L. , Migliori V. , Silengo M. , Franceschini P. , Andria G.
Published: July 2010

We describe a family with two male members showing an X/Y translocation (karyotype: 46, Y, der(X)t(X;Y)(p22;q11)). At physical examination both patients showed ichthyosis, mental retardation and dysmorphic features. Chondrodysplasia punctata and short stature were present in one case. Direct DNA analysis, using a steroid sulphatase cDNA probe, was performed in one patient, his mother and sister, both carriers of the translocation. We found that the translocated region of the Y chromosome includes the steroid sulphatase pseudogene. These results suggest that in our patients the X/Y translocation may be derived from a recombinational event between homologous regions located on the short arm of the X chromosome and the long arm of the Y chromosome. Clinical and molecular studies on the present family add further information for the construction of a tentative physical map of the distal Xp.