bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma lipids in two indigenous Arctic populations with low risk for cardiovascular diseases
Authors: Young T. Kue , Nikitin Yuri P. , Shubnikov Eugene V. , Astakhova Tamara I. , Moffatt Michael E. K. , O'Neil John D.
Published: June 2005

The distribution of plasma lipids and their sociodemographic and metabolic correlates were investigated in two Arctic indigenous populations based on two health surveys conducted during 1990–1991 among adults in eight Inuit communities in the Keewatin region of the Northwest Territories, Canada (n = 387), and in four communities in the Chukotka region in the Russian Far North (n = 362). For comparison, data from the Canadian Heart Health Survey were used. The age‐sex‐specific mean total and low‐density lipoprotein (LDL)‐cholesterol levels among Inuit in northern Canada either do not differ significantly from the Canadian national population, or, in the case of younger Inuit women, are higher than in Canadians. This represents a temporal change from the results of earlier studies. Chukotka Natives tend to have the lowest total cholesterol (TC) and LDL values of the three populations. The two indigenous populations still enjoy considerably lower levels of triglycerides (TG) and higher levels of high density lipoprotein (HDL) cholesterol than observed in Canada, with the exception of younger Inuit women whose mean TG levels are not significantly different from those of Canadians. The proportion of individuals at risk for ischemic heart disease because of high TG (≥2.3 mmol/L) is 20% among Canadian men but only 2% and 0% among the Arctic Natives, and 11% among Canadian women compared to 6% and 3% in the Keewatin and Chukotka regions, respectively. Such sociodemographic factors as education and marital status do not have a substantial and consistent effect on plasma lipid levels. Women with higher education have lower HDL (in Keewatin) and higher TG (in Chukotka), significant only at the 0.10 level. Among Chukotka men those who reported a lineage without nonindigenous admixture have a higher HDL level (P = 0.048). No difference between the admixed and nonadmixed can be found in the Keewatin. Smoking status has no significant effect on any of the lipid fractions in either population. The two Arctic populations demonstrate an association of some plasma lipids with blood pressure and indices of obesity and central fat patterning commonly observed in other populations. However, plasma glucose does not increase in tandem with increasing levels of lipids, contrary to that observed in the general Canadian population. © 1995 Wiley‐Liss, Inc.
Use of cortisol as a stress marker: Practical and theoretical problems
Authors: Pollard Tessa M.
Published: June 2005

Human biologists have shown increasing interest in the use of cortisol as an objective marker of stress in recent years. This paper reviews both practical and theoretical problems raised by this approach. The methodology of cortisol assessment using urine, saliva, and plasma is considered. There are many practical problems involved in obtaining good measures of cortisol, although the availability of salivary assays offers a promising way forward. Theoretical issues are of greater concern. Results of laboratory studies led to the hypothesis that cortisol is elevated when an individual is distressed. However, relatively little work has been done on cortisol variation in “real life,” and the results of such studies do not, in general, conform to this hypothesis. It is concluded that the determinants of cortisol variation are not well understood. For example, cortisol level may be as much influenced by positive emotions as by negative emotions usually identified with stress. Further documentation of cortisol variation in everyday life is needed, and at present it is premature to use cortisol level as a marker of stress. © 1995 Wiley‐Liss, Inc.
Impact of seasonal variation in food availability and disease stress on the health status of nomadic Turkana children: A longitudinal analysis of morbidity, immunity, and nutritional status
Authors: Shell‐Duncan Bettina
Published: June 2005

The possible influence of seasonal variations in rainfall, resource availability, and morbidity on immune function and nutritional status was examined in a longitudinal study of 54 nomadic Turkana children, 6 months to 10 years of age. The highly seasonal nature of rainfall in the arid semidesert environment of the Turkana District, northwestern Kenya, was associated with varying levels of animal milk production and meat and blood consumption. Despite significant seasonal variation in rainfall and food availability, the nutritional status of Turkana children, assessed through various anthropometric indicators, showed only moderate, if any, decline in the dry season. Rather, the data indicated that Turkana Children suffer from chronic mild‐to‐moderate malnutrition. In addition, analyses of cellular immunocompetence of the children, recognized to be a functional index of nutritional status, revealed extremely high levels of immunosuppression Year‐round. Significant monthly variation in the levels of acute respiratory and gastrointestinal infections among children were found, although averages across seasons were not significantly different and did not correspond with fluctuations in rainfall or resources availability. Instead, periodic spikes in the prevalence of morbidity occurred against an already high level of infectious endemicity. The results indicate that food availability is not likely to be the sole determinant of nutritional status and that infection may be an important contribtor to the high levels of nutritional and immunological stress among nomadic Turkana Children. © 1995 Wiley‐Liss, Inc.
Estimates of aging and secular changes using total arm length
Authors: Sethi Harinder K. , Sidhu L. S. , Singal Pushpa
Published: June 2005

Stature, total arm length, and subischial length were studied in a cross‐sectional sample of 387 working (career women) and 460 nonworking women (housewives), 20–75 years of age, from one endogamous group, the Khatris. Statural decrease due to aging was separated from secular effects by using total arm length, which was least affected by aging. The rate of loss in stature due to aging was 0.142 cm/year in the working women and 0.140 cm/year in the nonworking women. Both estimates are significantly different from zero. After adjusting stature for estimated aging effects, the resulting secular estimates were 0.004 cm/year in working women and 0.01 cm/year for nonworking women, both of which do not significantly differ from zero. © 1995 Wiley‐Liss, Inc.
Demography in biological anthropology: Human population structure and evolution
Authors: Lasker G. W. , Kaplan Bernice A.
Published: June 2005

The fact of human evolution is evident in the biological variation caused by the pattern of lines of descent. Theories of human evolution are the explanations of the fertility and mortality differentials that determine patterns of variation at the subspecific level. Migrations also influence the patterns. Because human beings plan migrations and marriages, theories relying solely on selective advantage and gene diffusion do not fully account for the observed patterns. These patterns can be interpreted through time and space as dense thickets of descent lines, often clustered into local fascicles held together by inbreeding. The patterns of descent lines are thus punctuated by births, sometimes ended by extinction of lines, but marked also by rich interconnections of the fascicles by filaments that represent marital migration. The patterns are neither solely of racial isolates nor of simple diffusion, but are the result of the complex sociocultural events that influence genetic demography, a field of study that some of Ed Hunt's work foreshadowed. © 1995 Wiley‐Liss, Inc.
Age at menarche as an indicator of the socioeconomic situation of rural girls in Poland in 1967, 1977, and 1987
Authors: Łaska‐Mierzejewska Teresa
Published: June 2005

Village girls, 9.5–18.5 years of age, inhabiting various regions of Poland, were surveyed in 1967 (n = 7,886), 1977 (n = 7,771), and 1987 (n = 11,479). Based on the source of income of the families, three groups were identified: farmers, farmer‐workers, and nonfarmers. The girls were also divided on the basis of the number of children in the family and education of their fathers. In all three surveys, the earliest age at menarche was observed in girls from the nonfarmer group and the latest in girls from the farmer group. In 1987 the ages at menarche were 13.27 ± 0.03 years and 13.58 ± 0.04 years, respectively. The rapid acceleration of menarcheal age (0.64 year) between 1967 and 1977 was halted, and perhaps, reversed from 1977 to 1987 (−0.06 year), reflecting the severe social and economic crisis in Poland. The later menarcheal ages observed in the last decade occur mainly among girls from families with four and five children. Girls from better educated rural families were more affected by the crisis than girls from families in which fathers have only an elementary or vocational training education. © 1995 Wiley‐Liss, Inc.
Basal metabolic rate of inuit
Authors: Rode Andris , Shephard Roy J.
Published: June 2005

Basal metabolic rates (BMR) at the end of the winter of 1981–1982 were determined in both Inuit and subjects of European ancestry resident in Igloolik, N.W.T. (69°40'N, 81°W). Values for the Inuit sample (22 females, 14–53 years, and 30 males, 14–70 years) exceeded published body surface area norms by some 16–18%; they also exceeded the body mass norms of Schofield (1985) by 9–10%. In contrast, readings on the six subjects of European ancestry, obtained by the same observer, using the same Douglas bag technique, agreed closely with both sets of published norms. When data were expressed per unit of lean body mass, values were again 10–12% higher in the Inuit. Concomitant recordings of heart rate did not suggest that the BMRs of the Inuit subjects were increased by anxiety. Contrary to findings in the subjects of European ancestry, BMRs appeared to be higher in the elderly than in young and middle‐age Inuit. This could reflect two consequences of a more traditional lifestyle among the older members of the Igloolik population: greater exposure to a very cold external environment, and greater consumption of “country” foods rich in protein and fat. © 1995 Wiley‐Liss, Inc.
An etiological survey of the severely retarded Hertfordshire children who were born between January 1, 1965 and December 31, 1967
Authors: Laxova Renata , Ridler M. A. C. , Bowen‐Bravery Marry , Opitz J. M.
Published: June 2005

An etiological survey is presented of all severely retarded children living in Hertfordshire, at home and in residential care, born between January 1, 1965, and December 31, 1967. One hundred and forty‐six children (87 boys and 59 girls) were ascertained, out of a total population of 46,960, with a prevalence of 1 in 320 or 3.1 per 1,000. Approximately 1/3 (47) had the Down syndrome, 1 per 1,000 population.

It was possible to establish a diagnosis in a further 45 cases, which included 1 additional case of autosomal chromosome abnormality and 7 each of autosomal dominant, recessive and X‐linked conditions; 17 were associated with presumed multifactorial etiological factors; in 6 the condition was thought to have been caused by an environmental agent. It was not possible to establish a cause in the remaining 54 cases.

Recurrence risks of severe mental retardation in cases where it is impossible to establish a definite diagnosis are discussed and the potential value, for genetic counseling purposes, of categorizing such patients into broad symptomatological groups, is suggested.
Duplication 2q33→2q37 due to paternal ins (12;2) translocation
Authors: Dennis N. R. , Neu R. L. , Bannerman R. M. , Francke U.
Published: June 2005

An 18 month‐old boy with partial duplication of the long arm of chromosome 2, based on a paternal balanced translocation, 46,XY,ins (12,2)(q23;q33q37), is described and compared with five previously reported cases. These children have in common a short nose with broad flat bridge and small anteverted nostrils, long upper lip, low‐set ears, and minor digital anomalies.
Dyslexia: Search for phenotypic and genetic heterogeneity
Authors: Omenn Gilbert S. , Weber Bruce A. , Hall Judith G.
Published: June 2005

Dyslexia, or specific reading disability, has been shown in many studies to be familial, though no simple mode of inheritance accounts for all pedigrees. It is likely that the difficulties of genetic analysis are due to heterogeneity within the phenotype. We have undertaken a series of studies of normally intelligent children with dyslexia and their families in a search for phenotypic and genetic evidence of heterogeneity. Family histories with specific attention to difficulties in learning to read and spell were taken for 21 families. School test results were available for probands. Spelling was analyzed and anecdotal information assessed to determine whether visual or auditory difficulties predominated. Among the probands, 11 had predominantly visual problems (with preference for orally presented material) and phonetic spelling errors; 7 had predominantly auditory problems (with preference for visually presented materials), mispronunciations, and dysphonetic spelling errors; and 3 had mixed features. Visual and auditory evoked responses were measured on all the probands and some of the family members, in a search for neurophysiological evidence of abnormality or asymmetry of response. No significant differences were found between hemispheres, between those with visual‐ and those with auditorypredominant dyslexia, or between left‐handed and right‐handed individuals. Both anecdotal family histories and spelling performances provide suggestive evidence that dyslexic patients may be delineated into subgroups with predominantly visual or predominantly auditory impairment and that these subtypes may be under separate genetic predisposition. Further neurophysiological investigation will be required to devise ways of identifying cases before learning disability becomes an educational problem.
The syndromology of anorectal malformation (atresia, stenosis, ectopia)
Authors: Pinsky Leonard , Opitz John M.
Published: June 2005

The syndromes, associations, and developmental field defects that include anorectal dysgenesis (atresia, stenosis, ectopia) as a principal or facultative sign are discussed. Most of these disorders are identifiable by their genetic or teratogenic etiology, their distinctive phenotype, or both. Their precise diagnosis is crucial for estimation of recurrence risk and other aspects of reproductive counseling, and it is essential for classificatory progress. The “VACTERL association” should not be used to label a patient with anorectal malformation and other anomalies except by exclusion; this rule is particularly relevant when the patient lacks tracheoesophageal malformation. The degree (or variety) of anorectal malformation that occurs in a given pattern of multiple congenital anomalies may be inconstant. Furthermore, anorectal malformation may be a solitary expression of a familial syndrome.
α‐L‐fucosidase in cultured bone marrow fibroblasts from fucosidosis patients
Authors: Beratis Nicholas G. , Hirschhorn Kurt , Opitz John M.
Published: June 2005

Bone marrow fibroblasts were cultured from two patients with fucosidosis type 2, six control subjects, and three patients with other lysosomal disorders. Optimal conditions for measuring α‐L‐fucosidase activity in lysates of these cells with the fluorogenic substrate 4‐methylumbelliferyl‐α‐L‐fucoside were established. The pH profile of normal bone marrow fibroblasts showed three peaks and a shoulder of enzymatic activity, with maximum activity at pH 4.75. In cells derived from fucosidosis patients two peaks of apparent α‐L‐fucosidase activity were obtained; the pH optimum was 4.5. α‐L‐Fucosidase activity (mean ± SD) in the fucosidosis and control bone marrow fibroblasts was 2.5 and 312.4 ± 10.9 nmoles 4‐methylumbelliferone per milligram protein per hour, respectively. A reduction in the apparent specific enzymatic activity in the fucosidosis cells was observed by using increasing concentrations of cellular protein in the assay system. Mixing experiments between normal and fucosidosis cells gave the expected activities. These findings indicate that cultured bone marrow fibroblasts can be used for the diagnosis and study of fucosidosis.
Analysis of the gross anatomical variations found in four cases of trisomy 13
Authors: Colacino Sharon C. , Pettersen James C. , Opitz John M.
Published: June 2005

The variations and defects observed during detailed gross anatomical dissections of four cases of trisomy 13 are described. Emphasis is on the muscular system where previously undocumented variations, absences, and supernumerary elements were observed. A muscle phenotype which includes absence of palmaris longus, palmaris brevis, plantaris, and peroneus tertius, the presence of pectorodorsalis muscles and muscles from the central tendon of the diaphragm to the pericardium near the pulmonary veins, and variations in the extensor indicis, extensor carpi radialis longus and brevis, biceps, and suprahyoid muscles is discussed. The brain defects which include absent olfactory bulbs and tracts and hypoplastic commissures are compared to those defects seen in cases of alobar holoprosencephaly wherein severe defects of the ethmoid bone are concomitants. Previously well‐documented defects of the viscera are included.
Genetic and evolutionary fitness
Authors: Murphy Edmond A. , Elston Robert C.
Published: June 2005

The advantages and disadvantages of evolutionary fitness (probability that a single mutant line will not become extinct) and genetic fitness (mean fecundity) are compared. For deterministic processes the two are equivalent, but for stochastic branching processes they may be totally unrelated except that an absolute genetic fitness of unity or less implies an evolutionary fitness of zero. To know the variance as well as the mean family size does not in general uniquely determine the evolutionary fitness.

Except where genetic fitness is close to unity, the impact of selection is shown to be rapid for the binomial, Poisson, negative binomial, and truncated negative binomial distributions.

Evolutionary fitness, though somewhat cumbersome, has greater relevance to evolution, genetic counseling, and voluntary population control; but genetic fitness which is much easier to handle is the more appropriate measure where a large number of mutants is involved.

Some empirical data on the transmission of various types of characters from parent to child are analyzed to allow comparison of genetic fitness, Crow's index, and a Malthusian parameter, with evolutionary fitness. There is a fair, but far from perfect, agreement among them. Multiple correlation of evolutionary fitness with mean and variance of family size taken jointly suggests a much more satisfactory approximation. It thus appears that, at the least, the population geneticist cannot afford to ignore the variance (which is not adequately represented in Crow's index). These relationsips, based on two sets of data only may be accidental and should be invoked with caution. It seems more than likely that other aspects of the distribution of family size (eg, even higher moments) may contain relevant information in certain cases.
Familial correlations of longevity: An isolate‐based study
Authors: Philippe Pierre , Opitz John M.
Published: June 2005

Familial correlations for age at time of death have been computed in a French Canadian isolate. We show that parent‐offspring correlations as well as sib correlations are of the same order of magnitude as that between spouses for various age groups at death. It is suggested that heritability of survival is nearly zero. Observed variability in survival is interpreted as the effect of environmental differences acting upon age‐dependent genes.
A genetic analysis of the papillon‐lefèvre syndrome in a Jewish family from Cochin
Authors: Hacham‐Zadeh S. , Schaap T. , Cohen M. M. , Opitz John M.
Published: June 2005

The Papillon‐Lefèvre syndrome (PLS) is segregating in a large kindred of a Jewish isolate originating from Cochin, India. The frequency of the gene responsible for PLS among the Cochin Jews, 0.1, was estimated from the number of unrelated carriers in the isolate who married into the kindred. The obvious discrepancy between this apparently high gene frequency and the total absence of PLS in other kindreds of the isolate suggests that the syndrome may not behave as a simple autosomal recessive trait.
Cystinuria genotypes predicted from excretion patterns
Authors: Kelly Sally , Scriver Charles E.
Published: June 2005

Genotypes of 17 patients with cystinuria were predicted from data based on excretion rates of the families' obligate carriers. The methodology differed from that used by other investigators as it did not employ intestinal biopsy studies or loading dose measurements. The Type I form was more common than either Type II or Type III and frequently occurred in combination to give compound heterozygous genotypes with the Type III form.
Normal intelligence in two children with carpenter syndrome
Authors: Frias J. L. , Felman A. H. , Rosenbloom A. L. , Finkelstein S. N. , Hoyt W. F. , Hall B. D. , Opitz John M.
Published: June 2005

Previous reports have noted a constant association between the Carpenter syndrome (acrocephalopolysyndactyly, type II) and mental retardation. We report two patients with this condition with normal intelligence. These observations indicate that mental deficiency is not necessarily a component of the Carpenter syndrome and that early surgical correction of the craniosynostoses may improve the chances of normal mentality.
Cerebral gigantism and primary hypothyroidism: Pleiotropy or incidental concurrence
Authors: Sotos Juan F. , Romshe Carolyn A. , Cutler Edward A. , Opitz John M.
Published: June 2005

An 8.5‐month‐old baby girl had cerebral gigantism and primary hypothyroidism with generalized large muscles (the Kocher‐Debré‐Semelaigne syndrome). The significance of this association remains to be determined.
The Rieger syndrome
Authors: Jorgenson Ronald J. , Levin L. Stefan , Cross Harold E. , Yoder Freda , Kelly Thaddeus E. , Fraser Clarke
Published: June 2005

Fourteen patients with hypodontia and the ocular features of the Rieger syndrome were examined for the presence of systemic anomalies. A periumbilical defect that consisted of failure of the periumbilical skin to involute was seen in ten of the thirteen evaluated for the defect. Three others had scars over the umbilical area and had a history of surgery for herniation. In addition, four males in one family and one male from another family had hypospadias. None of several other anomalies reported to be components of the Rieger syndrome by other authors was detected in the fourteen patients. The mode of inheritance in the familial cases studied was compatible with autosomal dominance.

The results of this study indicate that the Rieger syndrome is an autosomal dominant syndrome whose cardinal features are hypodontia, goniodysgenesis, and failure of the periumbilical skin to involute properly.
Size and pericentric inversion heteromorphisms of secondary constriction regions (h) of chromosomes 1, 9, and 16 as detected by CBG technique in Caucasians: Classification, frequencies, and incidence
Authors: Verma Ram S. , Dosik Harvey , Lubs Herbert A. , Francke Uta
Published: June 2005

Eighty normal Caucasians were studied by CBG technique for estimation of size and inversion heteromorphisms of chromosomes 1, 9, and 16. Size heteromorphisms were classified into one of five sizes using 16p as a reference standard: very small, small, intermediate, large, and very large. Inversion heteromorphisms were also classified into 5 categories – eg, no inversion; partial inversion – minor; half inversion; partial inversion – major; and complete inversion. The frequencies of size heteromorphisms for chromosomes 1, 9, and 16 were 11.3%, 47.5%, and 7.5%, respectively. Thirty‐four chromosomes were found to have inversions. Of these, 16 were in chromosome 1, and 18 were in chromosome 9. No inversions were found in chromosome 16. An increase in the size of the h region was more frequently associated with inversion, suggesting that there is a possible relationship between size and inversion. For example, there were 118 chromosomes that were classified as “intermediate” by size; 23 (19.5%) had inversions. In contrast, there were 225 that were “small” in size, and only 10 (4.4%) had inversions. There was no significant difference between males and females for size and position heteromorphisms.
Kaufman oculocerebrofacial syndrome: Case report
Authors: Jurenka Stanislava B. , Evans Jane , Optiz John M.
Published: June 2005

The oculocerebrofacial syndrome was described from siblings of both sexes in 1971 by Kaufman. A 12‐year‐old child with a set of corresponding malformations is described. This would suggest that the original report did not describe a “private” syndrome.
Mutations affecting pigmentation in man: I. Neuroectodermal melanolysosomal disease
Authors: Elejalde B. Rafael , Holguin Jorge , Valencia Aurora , Gilbert Enid F. , Molina Jaime , Marin Gabriel , Arango Luis A. , Witkop Carl J.
Published: June 2005

We describe a syndrome identified in three consanguineous families who had two and probably four common ancestors five generations ago. The syndrome is characterized by profound dysfunction of the central nervous system, silver‐leaden colored hair, abnormal melanosomes and melanocytes, and abnormal inclusion bodies in fibroblasts, bone marrow histiocytes and lymphocytes which appear to represent abnormal lysosomal bodies.

Because of the biochemical relationships between melanin‐melanosomes and neuromelanin, we think that all the manifestations of the condition are related to and represent pleiotropic effects of a newly identified gene in man in its homozygous state.

Biochemical reactions of the cells of these patients indicate presence of tyrosinase in the melanosomes and show that the substance accumulated in cultured fibroblasts and in the bone marrow histiocytes is a PAS and Oil‐red‐O positive material but is Oil‐red‐O negative after extraction; it has the typical reactions of melanin with the Masson and Fontana stain, but cannot be considered typical melanin, since without stain it is colorless. The ultrastructural studies showed round granules with variable matrix, similar in fibroblast and bone marrow, and with variable intensity of reaction to osmium.

This mutation principally affects the neuroectoderm, but also the mesoderm.
Cytogenetic studies of a male with sporadic intestinal lymphangiectasia: 45,X/46,XY mosaicism with pseudo‐ and hyperdiploid subpopulations in cultured tissues
Authors: White Beverly J. , Crandall Clare , Flier Jeffrey S. , Raveché Elizabeth S. , Tjio Joe‐Hin , Summitt Robert L.
Published: June 2005

45,X/46,XY mosaicism was found in peripheral blood, bone marrow, and tissue cultures of an adult male with intestinal lymphangiectasia (IL). Turner phenotype was not present; his meiotic metaphase analysis was normal, and his dermatoglyphics resembled those of his family.

Ten separate tissue culture lines from three biopsies of skin and thyroid gland contained 45,X cells (14.8 to 78.3%). Autosomal aneuploidy, resulting in pseudo‐ or hyperdiploidy, was also present in 4.3 to 41.6% of the cells. A hyperdiploid clone with a 47,X,+10,+18 karyotype was found in 22.6% of cells in one line. A second hyperdiploid clone with a 48,X,+2,+18,+18 karyotype occurred in 7.6% of cells from another line containing a total of 41.6% pseudo‐ and hyperdiploid cells. Such clonal abnormalities were not typical of tissue cultures from other patients done in our laboratory.

Growth of our patient's tissue cultures was subnormal, and none proliferated beyond the fourth subculture. The significance of this observation remains to be determined. Our results do not allow us to conclude whether our patient's mosaicism of somatic tissues arose during embryogenesis, or whether it originated post‐natally. The secondary immunodeficiency which occurs in IL may explain persistence of cells with unusual combinations of autosomal aneuploidy in our patient's tissues.
Christ‐Siemens‐Touraine syndrome—a clinical and genetic analysis of a large Brazilian kindred: I. Affected females
Authors: Pinheiro M. , Freire‐Maia N.
Published: June 2005

A total of 27 women of a Brazilian kindred are described as having one or more signs of the Christ‐Siemens‐Touraine syndrome. The history and physical examination were supplemented by four sweat tests and dermatoglyphic analysis. It is suggested that this syndrome has two forms – a major form (in males) and a minor one (in females). Two signs verified in some of our patients (mosaic patchy distribution of body hair and radial deviation of distal phalanges of index fingers) seem to be here described for the first time. A review of the literature shows a corrected sex ration between 1M:1.21F and 1M:2.38F among affecteds. Since the manifestation rate of the gene among carriers was estimated at about 0.70, the actual sex ratio is expected to be not lower than 1M:1.40F. Contrary to a general opinion, affected females outnumber affected males.
Christ‐Siemens‐Touraine syndrom—a clinical and genetic analysis of a large Brazilian kindred: III. Carrier detection
Authors: Pinheiro M. , Freire‐Maia N.
Published: June 2005

Detection of carriers of the Christ‐Siemens‐Touraine syndrome on the basis of data of physical examination has been possible in about 60–70% of the cases reported in 44 papers, including a large Brazilian kindred studied by the authors. Partial data, however, showed detection values ranging from 42% to 84%.
4p trisomy syndrome: Report of 4 additional cases and segregation analysis of 21 families with different translocations
Authors: Crane James , Sujansky Eva , Smith Ann
Published: June 2005

Thirty reports of partial 4p trisomy have been published. The manifestations and cytogenetic findings in four additional cases from two families are described in the present paper. Segregation analysis has been performed on the 21 families reported to date. The risk of having unbalanced offspring was the same in carrier mothers and carrier fathers. The risk of trisomic offspring was 14%. Among phenotypically normal progeny, normal karyotypes and balanced translocation states occurred with about equal frequency.
Inborn errors of lysosomal catabolism—principles of heterozygote detection
Authors: Jolly R. D. , Desnick R. J.
Published: June 2005

Carriers of an inborn error of lysosomal catabolism can be recognized, as they have enzyme levels approximately half those of normal individuals. Of the various tissues readily available for assay, plasma and leuk ocytes and, in some situations, tears are preferred. Although mixed leuk ocytes have proved satisfactory in Tay‐Sachs screening programs, purified preparations of granulocytes or lymphocytes will allow better discrimination in most situations. Enzymes are assayed relative to some other reference parameter which must be a constant or highly correlated with test enzyme activity. In the two mass screening programs in operation, β‐hexosaminidase A and α‐mannosidase have both been assayed relative to total β‐hexosaminidase activity. Carrier detection is particularly important in X‐linked diseases. The techniques used mostly involve hair roots or fibroblasts and depend on random inactivation of the X chromosome. In the mucolipid oses II and III, in which there are a number of deficient enzymes in cells, carriers may be identified on the basis of the ratio of β‐hexosaminidase I1 and I2 to total hexosaminidase.
Pentasomy X with multiple dislocations
Authors: Dryer Randall F. , Patil Shivanand R. , Zellweger Hans U. , Simpson Jane M. , Hanson James W. , Aschenbrenner Carol , Weinstein Stuart L.
Published: June 2005

We describe a pentasomy X (49,XXXXX) patient whose multiple dislocations led to a consideration of the Larsen syndrome. Review of the 11 reported cases of pentasomy X showed that elbow dislocations are known to occur in this syndrome. Our patient is the first to present hypoplasia of the glenoid process with consequent shoulder dislocation. Clinical and radiologic findings of previously reported cases of pentasomy X are reviewed.
Partial trisomy 20 confirmed by gene dosage studies
Authors: Rudd Noreen L. , Bain Harry W. , Giblett Eloise , Chen Shin‐Han , Worton Ronald G.
Published: June 2005

We describe a female infant with multiple congenital anomalies and mental retardation, pre‐ and postnatal growth failure, microcephaly, unusual facial appearance, and minor skeletal anomalies, all very suggestive of the partial trisomy 20(p) syndorme. Although she was born to karyotypically normal parents, she had an extra small metacentric chromosome. Analysis of metaphase and prometaphase chromosomes by GTG banding and Giemsa 11 staining showed that the extra chromosome was a number 20 with a deletion of the distal end of the long arm. Gene dose studies of adenosine deaminase (ADA) and inosine triphosphatase (ITP) supported the cytogenetic interpretation.
Analysis of a large pedigree with elliptocytosis, multiple lipomatosis, and biological false‐positive serological test for syphilis
Authors: Weinberg J. B. , Hasstedt S. J. , Skolnick M. H. , Kimberling W. J. , Baty B.
Published: June 2005

Elliptocytosis, multiple lipomatosis, and biological false‐positive serological test for syphilis (BFPSTS) were found in a single individual. One hundred eighty relatives were tested for the three diseases: 74 were typed for seven blood group antigens, and 58 were typed for four electrophoretic enzyme markers. Likelihood analysis of the pedigree data confirmed independent dominant inheritance for elliptocytosis and lipomatosis. BFPSTS appears dominant, but the analysis was inconclusive. No linkages were found between any disease gene and any marker gene. Two female pedigree members with BFPSTS developed systemic lupus erythematosus, a finding in agreement with the previously described association. The analysis did not lead to any conclusions about the causal relationship between the two traits.
Investigation of acephalus
Authors: Deacon J. S. , Machin G. A. , Martin J. M. E. , Nicholson S. , Nwankwo D. C. , Wintemute R.
Published: June 2005

We report twins, one of whom was diagnosed as grossly abnormal by ultrasound at 28 weeks' gestation. Postmortem angiographic investigation of this acardiac twin and of the inter‐fetal placental anastomoses are reported. The acardiac fetus had a 45,X chromosome constitution, while the other twin had apparently normal chromosomes (46,XX). The association of chromosome anomaly with holoacardius acephalus is discussed.
Sex chromosome aneuploidy and anthropometry: A new proportionality assessment using the phantom stratagem
Authors: Miller R. , Ross W. D. , Rapp A. , Roede M. , Opitz John M.
Published: June 2005

Reported anthropometric data on 121 subjects with 47, XYY, 47,XXY, 47,XXX, and 45,X aneuploidies were compared to those from 578 male and female control subjects by use of a single, unisex reference person (“phantom”). Subjects and controls were geometrically scaled to a standard stature of 170.18 cm, thus eliminating variance due to height. Deviations of anthropometric variables from specified phantom values were expressed as standard z‐scores. By comparing z‐scores of individual aneuploidy classes with those of their controls, further differences in proportionality came to light. The stratagem disclosed a systematic proportionality pattern between subjects and controls which appeared to be related to each specific sex chromosome aneuploidy. The phantom stratagem for proportional growth assessment appears to merit further use in genetic investigations where individual differences in size and shape confound the analysis of anthropometric data.
Huntington disease: Linkage analysis with age‐of‐onset corrections
Authors: Hodge Susan E. , Spence M. Anne , Crandall Barbara F. , Sparkes Robert S. , Sparkes Maryellen C. , Crist Michol , Tideman Susan
Published: June 2005

Eleven extended pedigrees segregating autosomal dominant Huntington disease (HD) were analyzed for linkage with 15 gene markers. A straight‐line age correction (STLN), fitted roughly to published age‐of‐onset data but excluding the oldest and youngest ages, was used. The results failed to confirm a positive lod score reported by Brackenridge et al [1978] between HD and haptoglobin (Hp); our lod scores, taken alone, would rule out this linkage. No lod score in our study exceeded 0.40. Three informative markers, adenosine deaminase (ADA), Hp, and MNSs, were used to compare results obtained by employing different age corrections during lod score calculation. In addition to STLN, a least‐squares line (LSQR) and a cumulative normal curve (CUMN) were used. CUMN was assumed to be the most accurate, since it fitted the data most closely. For comparison, two methods involving no age correction were also examined: one in which all unaffected persons were uniformly assigned a 50% penetrance (NONE) and one in which all younger at‐risk persons were removed from the analysis (REMV). NONE and REMV distorted lod scores, in some cases strikingly. More importantly, they also sometimes biased the estimate of the recombination fraction. In contrast, STLN and LSQR gave results generally very similar to those found using CUMN. Thus, it was concluded that the exact shape of the age correction used is not critical to linkage analyses, but that failure to use any correction may lead to unacceptable results.
Utility and limitations of chromosome banding in pre‐ and postnatal service cytogenetics
Authors: Fisher N. L. , Starr E. D. , Greene T. , Hoehn H. , Kaye Celia
Published: June 2005

This report analyzes detection rates of chromosome aberrations as a function of staining technique. Of 1,717 peripheral lymphocyte cultures processed by a midsize service cytogenetics laboratory, 23 chromosomal aberrations (1.3%) would not have been detected without the use of either R‐banding or G‐banding. These 23 cases comprise 21 of 64 non‐Robertsonian structural autosomal changes and two of 68 gonosomal aberrations. In contrast, in 1,634 amniotic fluid cell cultures only one balanced rearrangement (0.06% of all cases) would not have been detected without banding. Combined with incidence rates from newborn cytogentic screenings, these figures suggest that among 10,000 prenatal diagnoses for advanced maternal age, at most one chromosomally unbalanced fetus would be missed if banding were not routinely applied. Because of savings in time and possible automation, it is estimated that discretionary rather than routine use of chromosome banding in prenatal cytogenetics would allow for detection of at least twice as many age‐related aneuploidies. In view of sharply rising demand for prenatal cytogenetic services, a discretionary approach might therefore assure a more equitable distribution of limited cytogenetic resources.
Characteristics of births in each cycle of the bimodal monthly distribution in cystic fibrosis
Authors: Brackenridge C. J. , Miller James R.
Published: June 2005

The bimodal monthly birth distribution of patients with cystic fibrosis (CF) in Victoria, Australia, is shown to be similar within and among sibships, so that intrafamilial concentration of births around March (mode 1) or September (mode 2) cannot explain the observed periodic pattern. Mode 2 children are subject to a higher stillbirth rate and have younger maternal ages than mode 1 children. A sample of persons dying with CF in England and Wales displaying a similar bimodal birth pattern is shown to have a reduced infant survival rate for males of mode 2. These findings suggest that two annual cycles are a more appropriate model than a six‐monthly cycle. An attempt is made to equate mode 1 in the northern hemisphere with mode 2 in the southern hemisphere by pointing out the high perinatal death rate in the former and the high still‐birth rate in the latter.
Invited editorial essay: The legal implications of refusing to provide prenatal diagnosis in low‐risk pregnancies or solely for sex selection
Authors: Wright Ellen E. , Shaw Margery
Published: June 2005

As more people learn about prenatal diagnosis, medical personnel are increasingly being asked to perform these procedures in both low‐risk pregnancies and for purposes of sex selection. Analysis of present legal rules illustrates that it is highly unlikely genetic counselors will be subjected to legal liability for refusing to provide prenatal diagnosis in these situations. This freedom from liability will probably continue into the foreseeable future, despite recent developments in the areas of informed consent and allocation of scarce medical resources that tend to limit the traditionally broad deference given to medical personnel.
Stimulation of amniotic fluid cell growth by cartilage growth factor
Authors: Golbus Mitchell S. , Djalali Mahmoud , Klagsbrun Michael , Kaback Michael M. , Levenson Richard M. , Epstein Charles J.
Published: June 2005

Cartilage growth factor (CGF) stimulates the growth of primary and secondary cultures of human amniotic fluid cells. Over a 14–16‐day period there is an approximately 70% enhancement in the number of cells in primary cultures and a 170% increase in secondary cultures. Neither the karyotype nor the specific activities of lysosomal enzymes are altered by the presence of CGF in the medium.
Autosomal‐dominant inheritance of distal arthrogryposis
Authors: McCormack Michael K. , Coppola‐McCormack Patricia J. , Lee Ming‐Liang , Hall Judith G.
Published: June 2005

We report on a 32‐year‐old Italian man, his 5‐year‐old daughter, and his 3 1/2‐year‐old son, all of whom had congenital joint contractures. Each has severe ulnar deviation of fingers and soft‐tissue contractures of both hands; and each had bilateral clubfeet at birth. The father is short in stature, as are the children, who also have delayed carpal ossification. The findings in this family suggest autosomal‐dominant inheritance of the condition. The clinical features are consistent with the condition currently referred to as “distal” arthrogryposis.
Assessment of prospective genetic counseling in the Ferrara area
Authors: Barrai I. , Vullo C. , Opitz John M.
Published: June 2005

A group of 613 heterozygotes for beta thalassemia (267 married, 346 unmarried) who were screened mostly at elementary school age, were identified and interviewed at the average age of 23.7 years to assess their knowledge of the heterozygous state and its implications.

It was found that 83% recalled some information about their heterozygous state; only 60% had some information about the meaning of being heterozygous, and only 26% said they knew of some relationship between Cooley's anemia and the heterozygous state for beta thalassemia.

In the married group, the proportion of those having married another carrier was in agreement with random mating expectations. It was concluded that there is ample room for improvement in the procedures of delivery of prospective genetic counseling at the population level in this area.
Genetic analysis of von Willebrand's disease in two large pedigrees: A multivariate approach
Authors: Goldin Lynn R. , Elston Robert C. , Graham John B. , Miller Connie H. , Murphy Edmond A.
Published: June 2005

Clinical and laboratory data, including polymorphic marker traits for linkage analysis, were collected from two large multigenerational families segregating for von Willebrand disease. A new approach to the identification of gene carriers in these families, combining pedigree segregation analysis with multivariate discriminant analysis, is applied. Whereas individually the clinical symptoms and the factor VIII related activities could not distinguish between hypotheses, it was possible to find a discriminant function showing consistency of the data with a dominant gene hypothesis, but not with a recessive gene or an environmental hypothesis. This function is estimated to lead to 3.2% and 5.5% minimum misclassification of the genotypes, respectively, in the two families. The discriminant function could be used for other families, but is should be calibrated for the specific population in which it is used.

Among the markers investigated, GPT is the most likely to be linked to von Willbrand's disease, with a maximum lod score of about unity at 15% recombination.
Application of benefit‐to‐cost analysis to an X‐linked recessive cardiac and humeroperoneal neuromuscular disease
Authors: Wright M. L. , Elsas L. J.
Published: June 2005

Benefit‐to‐cost analysis (using standard economic methods) and the predictive tools of genetics are important in the assessment of genetic services for high burden, single gene disorders. We have studied 6 generations of a 167‐member, stable, North Georgia kindred at risk for X‐linked recessive humeroperoneal neuromuscular disease with cardiac conduction defects. This disorder began in affected males in the teen years, with total disability expected by the 3rd decade and death by age 50. Using known fecundity rates and Mendelian probabilities, 26.6 heterozygous females and 9.4 hemizygous affected males were expected in the currently developing generation. We compared the compensatory costs for families with affected males against costs of genetic intervention for this disorder. All costs and benefits were discounted to present values at 6% and 10% and a benefit‐to‐cost ratio was derived. At a 6% discount rate the benefit‐to‐cost ratio was 21 to 1 while at a 10% discount rate the benefit‐to‐cost ratio was 14 to 1.

We conclude that although this is an unusual X‐linked muscular dystrophy, it constitutes a prototypic public and private expense which is largely preventable. The method of cost accounting within pedigrees has wide applicability. The results reemphasize the economic benefit of comprehensive public health programs in genetics, particularly in areas with stable, high risk‐populations.
The quantitative genetics of disease: Ambiguities
Authors: Murphy Edmond A. , Optiz John M.
Published: June 2005

Here I review briefly some terms appropriate to the formal discussion of the genetics of disease. The motive for writing is that at least three kinds of participating experts are involved: pathologists, geneticists, and statisticians. Not only may some of the terms used in one field be unfamiliar to experts from another, the same term may be used in diverse ways among, or even within, fields. Such ambiguity may create illusory understanding or even frank confusion.
GENFILES: A computerized medical genetics information network. III. CHROMO: The cytogenetics database
Authors: Loughman William D. , Mosher Douglas C. , Epstein Charles J.
Published: June 2005

The computer database CHROMO is the cytogenetic branch of the GENFILES medical genetics information system. Complete cytogenetic laboratory data are maintained in a format that allows detailed searches of client records. Both the standard and extended Paris nomenclature are used.
Partial 3q trisomy due to an unbalanced 3/10 translocation
Authors: Blumberg Bruce , Moore Robin , Mohandas T. , Francke Uta
Published: June 2005

A newborn with partial 3q trisomy is reported. This female, small for gestational age, had multiple dysmorphic features, including turricephaly, microcephaly, broad and flat nasal bridge, anteverted nares, small ears, short limbs, bilateral transverse palmar creases, and fifth finger clinodactyly. The patient expired at 20 hours of age. An autopsy demonstrated duplication of the vagina and cervix, a bicornuate uterus, and streak ovaries. Cytogenetic studies revealed the patient to be trisomic for the portion of 3q distal to band 21 [46,XX,‐10,t(3;10) (q21;p15)]. The father was found to carry a balanced 3/10 translocation [46,XY,t(3;10) (q21;p15)].