bluuebunny/crossref_metadata_2025 huggingface dataset:
Assortative mating by body height and BMI: Finnish Twins and their spouses
Authors: Silventoinen Karri , Kaprio Jaakko , Lahelma Eero , Viken Richard J. , Rose Richard J.
Published: September 2003

Assortative mating by body height and weight is well established in various populations, but its causal mechanisms remain poorly understood. We analyzed the effect of phenotypic assortment and social homogamy on spousal correlations for body height and body mass index (BMI, kg/m2). Our data derived from a questionnaire administered to the adult Finnish Twin Cohort in 1990 (response rate 77%) yielding results from 922 monozygotic and 1,697 dizygotic adult twin pairs who reported information about their body height and weight and that of their spouses. Assortative mating was evident for body height and BMI. For body height, the effects of social homogamy (0.24 in men and 0.29 in women) and phenotypic assortment (0.27 and 0.28, respectively) were about the same. For BMI, the effect of social homogamy was stronger (0.31 in men and 0.28 in women) than the effect of phenotypic assortment (0.13 in both men and women). When assortative mating was taken into account, shared environmental factors had no effect on phenotypic variation in body height or BMI. Our results show that assortative mating needs to be considered in population genetic studies of body height and weight. Am. J. Hum. Biol. 15:620–627, 2003. © 2003 Wiley‐Liss, Inc.
Quantifying trabecular orientation in the pelvic cancellous bone of modern humans, chimpanzees, and the Kebara 2 Neanderthal
Authors: Martinón‐Torres María
Published: September 2003

The adaptive nature of bone lies in its ability to respond to the environment by conforming and reshaping itself constantly to accommodate life‐time stresses experienced throughout daily activities. In order to keep strains within the bone as uniform and isotropic as possible, the trabecular orientation is determined by forces acting on the bone through adaptive remodeling. Hence, the preserved structure of bones may contain direct information about the forces they may have undergone. Some authors (Correnti [1952], Atti Acc Naz Lincei 12:518–523, [1955] Riv Antrop 42:289–336; Macchiarelli et al. [1999] J Hum Evol 36:211–232, [2001] Cambridge, UK: Cambridge University Press) have described in detail the trabecular systems of the hip bone in different primate species and have identified a gait‐related system above the acetabulum with substantial differences across species (Macchiarelli et al. [1999]; Rook et al. [1999] Proc Natl Acad Sci USA 96:8875–8879). The aim of this study was to quantify trabecular orientation above the acetabulum to test the hypothesis that hominoid biomechanical behavior is recorded in the cancellous bone. The pelvic bones of 23 archaeological adult modern humans (12 females, 11 males), 20 adult Pan troglodytes (10 females, 10 males), and one adult male Neanderthal were radiographed and digitized. Fast Fourier transforms (FFTs) of the regions of interest in the corpus of the ilium were performed, with the angular distribution of the trabeculae quantified. All species displayed a constant and periodic orthogonal arrangement in the trabeculae with differences in the pattern of dominance between the arcades oriented along the 0° or the 90° axes. The variation in the FFT spectrum between species is discussed in the light of distinctive biomechanical features. Am. J. Hum. Biol. 15:647–661, 2003. © 2003 Wiley‐Liss, Inc.
Inbreeding coefficients and degree of consanguineous marriages in Spain: A review
Authors: Fuster Vicente , Colantonio Sonia Edith
Published: September 2003

The contribution of consanguineous marriages corresponding to uncle–niece or aunt–nephew (C12), first cousin (C22), first cousin once removed (C23), and second cousin (C33) to the inbreeding coefficient (α) was analyzed from a sample of Spanish areas and periods. Multiple regressions were performed taking as independent variables the different degrees of consanguinity previously selected (C12, C22, C23, and C33) and as dependent variable the inbreeding coefficient (α). According to the results obtained for any degree and period, rural frequencies always surpass urban. However, the pattern is similar in both areas. In the period where consanguinity was more elevated (1890–1929) the C22/C33 ratio increased. Its variation is not due to C22 and C33 changes in the same way. In rural areas, this ratio surpasses the expected value by a factor of 2–3, but in urban areas it was 7–10 times larger, in some cases due to migration. While in rural Spain the C33 frequency was ∼1.5 times C22, in cities C22 was 1.5 times C33. The best fit among the various types of consanguineous matings and α involves a lineal relationship. Regardless of the number of variables contributing significantly to α, C22 matings are always present. Moreover, their standardized (β) coefficients are the highest. The above indicates that this consanguineous relationship conditions the inbreeding coefficient the most. In the period of greater consanguinity, close relationships, uncle–niece C12, and first cousin once removed (C23) make a significant contribution to α. In rural Spain second cousins (C33) always significantly determined α; however, in cities the inbreeding variation was mainly due to C12 and C23. Am. J. Hum. Biol. 15:709–716, 2003. © 2003 Wiley‐Liss, Inc.
Effects of oral zinc supplementation on serum leptin levels in Ache males of eastern Paraguay
Authors: BRIBIESCAS RICHARD G.
Published: September 2003

Significant population variation has been demonstrated in serum leptin levels, independent of adiposity. Included within these populations, Ache males have significantly lower leptin levels compared to American subjects with comparable adiposity. The underlying causes of these differences are not understood but zinc has been shown to be an important regulator of leptin in humans and rodents. Zinc deficiency is associated with somatic wasting and significant declines in circulating leptin levels. Zinc deficiency is common in underdeveloped regions and may therefore contribute to low leptin levels among Ache men. To ascertain the potential role of zinc on Ache male leptin profiles, zinc supplementation was conducted to observe leptin responsiveness. Ache males were given daily oral zinc supplementation (50mg zinc gluconate) (n = 8) or placebo (n = 6) for 10 days. Serum leptin levels were measured on the first and last days of the treatment/placebo period. Despite supplementation exceeding triple the USDA recommended daily requirements, serum leptin levels did not change in the zinc‐supplemented group (P = 0.61) and were not significantly different from males receiving placebo (P = 0.72). It is concluded that zinc is not likely to be a contributing factor in male Ache leptin profiles and that other sources of variation such as chronic energetic stresses affecting leptin production and perhaps receptor number or sensitivity should be considered. Am. J. Hum. Biol. 15:681–687, 2003. © 2003 Wiley‐Liss, Inc.
Atherogenic lipid profiles in Filipino adolescents with low body mass index and low dietary fat intake
Authors: Kuzawa Christopher W. , Adair Linda S. , Avila Joesphine L. , Cadungog Joseph H.C. , Le Ngoc‐anh
Published: September 2003

This study reports mean lipid levels and their association with body composition, diet, and activity level in 300 male and 308 female adolescents (14–16 years) living in Cebu City, the Philippines. Participants were selected from the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a 1‐year birth cohort study begun in 1982–83. Lipid profiles suggest high cardiovascular disease (CVD) risk in this sample, despite low intake of dietary fat (22% for both sexes) and an absence of obesity (0.3% of sample). Mean lipid levels for males and females were, respectively, 153.2 mg/dl and 182.5 mg/dl for total cholesterol (TC), 91.9 mg/dl and 104.6 mg/dl for low‐density lipoprotein cholesterol (LDL‐C), 38.3 mg/dl and 41.3 mg/dl for high‐density lipoprotein cholesterol (HDL‐C, geometric mean), and 73.9 mg/dl and 79.6 mg/dl for triglycerides (TG, geometric mean). The atherogenic ratio of TC/HDL‐C was high at 4.16 and 4.55 for males and females. Adjusting for maturational changes, the body mass index (BMI) and skinfold measures were positively associated with most lipids in males. Among females, BMI and skinfolds related positively to LDL‐C and TG, and inversely to HDL‐C. Although males had a higher waist hip ratio (WHR), WHR only predicted lipid profiles in females. Activity level had a beneficial association with lipid profiles in both sexes, while dietary fat intake was positively associated with LDL‐C in males and with HDL‐C in females. In sum, diet, adiposity, and physical activity predict variability in lipid profiles in this adolescent Filipino population. However, the low fat intake and near‐absence of obesity raise questions about the causes of the high apparent risk for future CVD in this young population. Am. J. Hum. Biol. 15:688–696, 2003. © 2003 Wiley‐Liss, Inc.
Effects of developmental and adult androgens on male abdominal adiposity
Authors: McIntyre Matthew H. , Lipson Susan F. , Ellison Peter T.
Published: September 2003

We present results from 42 gay men who completed a survey including self‐measurement of waist circumference, height, and weight, in addition to providing saliva samples for the assay of testosterone, and a photocopy of the right hand for the measure of second‐to‐fourth digit length ratio (2D:4D), proposed as a means of approximating androgenic effects during development. The analyses were conducted as a test of the recent hypothesis, proposed by Abbott et al. ([2002] J Endocrinol 174:1–5), that high prenatal androgen exposure causes greater deposition of fat on the abdomen relative to other depots. We found support for this hypothesis in men, albeit in a limited sample and with self‐reported and self‐collected data. Am. J. Hum. Biol. 15:662–666, 2003. © 2003 Wiley‐Liss, Inc.
Impact of breastfeeding on anthropometric changes in peri‐urban Toba women (Argentina)
Authors: Valeggia Claudia R. , Ellison Peter T.
Published: September 2003

We present an analysis of the effect of lactation on average maternal anthropometric and body composition measures in a population of Toba women in Formosa, Argentina. This indigenous population is undergoing a continuing transition from a seminomadic hunter–gatherer lifestyle to a sedentary, peri‐urban one. Using a mixed‐longitudinal design, we measured monthly maternal body mass index (BMI), body fat percentage, and triceps and subscapular skinfold thickness between birth and the 18th month postpartum in 113 breastfeeding women. The pattern of change in postpartum body composition varied with maternal age. Adult women (20 years old and older) did not show significant changes in any of the anthropometric measures during the entire study. Older adult women (30 years old and older) consistently had the highest values in measures of BMI and percentage fat, and tended to retain weight postpartum. Adolescent subjects (19 years old and younger) tended to lose weight during the first 6 months postpartum but regain their prepregnancy weight by 12 months postpartum. The same patterns were observed for changes in body fat percentage and in skinfold thickness. We conclude that in this population the energetic stress of lactation does not pose a serious challenge to the maintenance of long‐term maternal energy balance or to short‐term energy balance in women over 20 years of age. From a public health perspective, postpartum weight retention in older women may represent a more serious health threat. The low level of energetic stress associated with lactation may also contribute to the relatively short duration of lactational amenorrhea in this population despite a cultural pattern of intensive breastfeeding. Am. J. Hum. Biol. 15:717–724, 2003. © 2003 Wiley‐Liss, Inc.
Salivary testosterone and body composition among Ariaal males
Authors: Campbell Benjamin , O'Rourke Mary T. , Lipson Susan F.
Published: September 2003

To determine if testosterone is negatively related to acute and/or chronic nutritional status among men in a subsistence society, saliva samples and anthropometric measures were compared among nomadic and settled Ariaal pastoralists of northern Kenya. Fifty‐six nomadic men and 62 settled men facing drought conditions, estimated ages 22–96 years, were sampled. Measures included height, weight, four skinfolds, and %body fat by bioelectric impedance (BIA). Saliva samples were assayed for testosterone using radioimmunoassay. Overall, both body mass index (BMI) (avg. = 17.8 ± 6.0 kg/m2) and salivary testosterone (T) levels (avg. am value = 176.8 ± 74.8 pmol/l) were low compared to values from Western populations. Comparison of the two subpopulations revealed no significant difference in height, weight, BMI, or lean body mass. However, nomadic males exhibited significantly smaller skinfolds. Evening, but not morning, salivary T values differed between the subpopulations. Age‐related changes in body composition included a significant decline in BMI with age, related to loss of body fat, but with little change in lean body mass. Age‐related declines in BMI and %body fat were more pronounced among the nomadic males. am salivary T values declined with age; again, the decline was significantly greater among nomadic males. pm salivary T levels showed no significant decline with age. When controlled for residence and age, salivary T was positively related to %body fat and WHR ratio, but not lean body mass. These results provide evidence that salivary T is related to acute nutritional status among males in an energetically stressed subsistence population, in accordance with life history theories of somatic allocation. Am. J. Hum. Biol. 15:697–708, 2003. © 2003 Wiley‐Liss, Inc.
Timing is everything: A reconsideration of fetal growth velocity patterns identifies the importance of individual and sex differences
Authors: Lampl Michelle , Jeanty Philippe
Published: September 2003

Fetal growth has been posited to follow a “timing hypothesis” sequence in which the second trimester favors a single growth velocity peak in body length and the third trimester accommodates a single growth velocity peak in weight accrual. To our knowledge, this proposition has never been tested with high‐frequency longitudinal ultrasound data from normally growing human fetuses. The present study examined whether fetal growth in leg length had its peak velocity at or about 20–26 gestational weeks and declined subsequently and whether estimated fetal weight velocity was maximal at or about 33 weeks and declined subsequently; if the greatest acquisition of leg length occurred in the second trimester and weight in the third trimester; and if birth outcomes reflected these relationships. The data in this study included approximately weekly longitudinal ultrasound data collected from 44 maternal/fetal pairs in Brussels, Belgium. Diaphyseal lengths of the femur and tibia provided information on leg growth and estimated fetal weight was assessed from the biparietal and occipital‐frontal head diameters and transverse and anterior–posterior diameters of the abdomen. Growth patterns were investigated from individual growth curves derived from daily growth velocity z‐scores. Paired t‐tests compared individuals' trimestral increments in leg length and fetal weight. Least‐squares regression models employing the robust procedure for repeated measurements were used to test for relationships between trimester, size, growth rates, and birth outcome, controlling for day of measurement, sex, maternal smoking, and gestational age at birth. The normal fetuses in this study grew by pulsatile patterns of leg and estimated weight acquisition, not a single peak and decline process. Greater incremental growth in estimated fetal weight occurred during the second trimester and leg length in the third trimester. Individual and sex effects were significant in growth velocity patterns. Girls grew with greater synchrony between leg and weight growth and were accelerated by comparison with boys, with faster leg growth predicting lower ponderal index by the second trimester. Birth outcomes were sex‐specific in timing effects and predictive variables. These results support the importance of sex‐specific analyses, reemphasize the common notion that girls grow faster than boys, and direct attention to cross‐talk between energy resources and growth. Am. J. Hum. Biol. 15:667–680, 2003. © 2003 Wiley‐Liss, Inc.
Laryngeal malformation in the Richieri‐Costa‐Pereira acrofacial dysostosis: Description of two new patients
Authors: Tabith Alfredo , Guedes de Azevedo Bento‐Gonçalves Cristina
Published: September 2003

We describe laryngeal malformations and voice disorders in two new patients with the autosomal recessive Richieri‐Costa and Pereira form of acrofacial dysostosis. This report confirms the data on the first five patients we had already presented in 1996. © 2003 Wiley‐Liss, Inc.
Identification of an autosomal recessive mode of inheritance in paediatric Behçet's families by segregation analysis
Authors: Molinari N. , Paut I. Koné , Manna R. , Demaille J. , Daures J.P. , Touitou I.
Published: September 2003

We have conducted a segregation analysis in order to characterise the transmission of Behçet Disease (BD), a multifactorial condition with a strong genetic component. Complete information about BD status and pedigree was obtained on 104 probands from our database. We used the criteria of the International Study Group for BD (ISBD) to delineate the clinical status of the sibs: possible BD (patients meeting two criteria), or ascertained BD (patients meeting at least three criteria). A proband was defined as “paediatric” when he/she completed ISBD criteria before/by the age of 16 years. Families were distinguished as paediatric (n = 67) (ascertained through a paediatric proband), and non‐paediatric (n = 37) ones. An Expectation Maximization (EM) algorithm was used to estimate the Mendelian segregation ratio P in nuclear families (two parents and their offspring). The maximum likelihood estimate: P̂ = 0.248, calculated in the paediatric data set, was consistent with the theoretical value of P = ¼ for autosomal recessive inheritance, whereas the P̂ value was 0.08 when using the non‐paediatric data set. Our work provides the first evidence of genetic heterogeneity in BD, and of the existence of a Mendelian entity in the paediatric BD subgroup. Previous studies failed to show any simple mode of inheritance in BD, probably because they were performed on the whole BD population. © 2003 Wiley‐Liss, Inc.
Fragile‐X syndrome and skewed X‐chromosome inactivation within a family: A female member with complete inactivation of the functional X chromosome
Authors: Heine‐Suñer D. , Torres‐Juan L. , Morlà M. , Busquets X. , Barceló F. , Picó G. , Bonilla L. , Govea N. , Bernués M. , Rosell J.
Published: September 2003

Fragile X syndrome is the most common form of inherited mental retardation. It is caused by the increase in length of a stretch of CGG triplet repeats within the FMR1 gene. A full mutation (> 200 repeats) leads to methylation of the CpG island and silencing of the FMR1 gene. We present here two sisters that are compound heterozygotes for a full mutation and a 53 repeat intermediate allele, one of them showing mental retardation and clinical features of an affected male (speech delay, hyperactivity, large ears, prominent jaw, gaze aversion), while the other is borderline normal (mild delay). Southern blot and FMRP expression analysis showed that the sister with mental retardation had the normal FMR1 gene totally methylated and no detectable protein, while her sister had 70% of her cells with the normal FMR1 gene unmethylated and normal FMRP levels. We found that the observed phenotypic differences between both sisters who are cytogenetically normal, are caused by extreme skewed X‐chromosome inactivation. Analysis of the extended family showed that most of the other female family members that carry a pre‐mutation or a full mutation showed some degree of skewing in their X‐chromosome inactivation. The presence of several family members with skewed X inactivation and the direction and degree of skewing is inconsistent with a mere selection during development, and suggests a genetic origin for this phenomenon. © 2003 Wiley‐Liss, Inc.
Multiple supernumerary ring chromosomes of different origin in a patient: A clinical report and review of the literature
Authors: Beverstock Geoff C. , Bezrookove Vladimir , Mollevanger Paul , van de Kamp Jacques J.P. , Pearson Peter , Kouwenberg Jan M. , Rosenberg Carla
Published: September 2003

We describe a patient with multiple congenital abnormalities exhibiting 2–5 supernumerary chromosomes per cells. A variety of FISH techniques were used to demonstrate that the markers are probably rings, lack detectable telomere sequences, and originate from different non‐acrocentric chromosomes, namely 6, 7, 10, 12, and 19. Such cases are extremely rare and this is only the 8th published report of an individual presenting three or more supernumerary chromosomes. We reviewed all available cases of multiple supernumerary chromosomes and the collective data indicate that multiple markers seem always to be rings of different origin. These results provide evidence that such multiple ring markers cannot possibly represent duplication or recurrence of an original structural rearrangement but must be derived with a common causality from different chromosomes. Possible mechanisms for the simultaneous production of multiple rings from different chromosomes are proposed, including the breakdown and rearrangement of a haploid complement shortly after fertilization in a triploid zygote. © 2003 Wiley‐Liss, Inc.
Experiences at the time of diagnosis of parents who have a child with a bone dysplasia resulting in short stature
Authors: Hill Victoria , Sahhar Margaret , Aitken MaryAnne , Savarirayan Ravi , Metcalfe Sylvia
Published: September 2003

Many studies have shown that, for families who are given the diagnosis of a disability, satisfaction with disclosure is an important element. Information given and the attitudes of the disclosing health professionals during this critical period have a significant effect on the coping and adaptation of the family. While most studies dealt with conditions involving intellectual disability or cancer, this study was conducted to explore parents' experience of being told that their child had a condition, such as a bone dysplasia, that would result in significant short stature. Semistructured interviews were conducted with 11 families who had children diagnosed with a bone dysplasia, specifically, achondroplasia (n = 9) and pseudoachondroplasia (n = 2). Families were recruited through the Bone Dysplasia Clinic at the Royal Children's Hospital, Victoria, Australia and via contact with the Short Statured People's Association of Victoria. Parents were asked about how they were told of their child's diagnosis, how they would have preferred to have been told, and what would have made the experience less distressing for them. Transcripts of the interviews were analyzed, and major themes were identified relating to the parents' experiences. Our data suggest that the manner in which the diagnosis is conveyed to the parents plays a significant role in their adjustment and acceptance. Provision of written information relating to the condition, possible medical complications, positive outlook for their child's future, and how to find social services and supports were some of the most significant issues for the parents. The multidisciplinary approach of the Bone Dysplasia Clinic was important to parents in the continued management of the families. © 2003 Wiley‐Liss, Inc.
Optic pathway gliomas in neurofibromatosis type 1: The effect of presenting symptoms on outcome
Authors: King Allison , Listernick Robert , Charrow Joel , Piersall Linda , Gutmann David H.
Published: September 2003

Children with neurofibromatosis type 1 (NF1) may present with optic pathway gliomas (OPG) that can progress to visual loss or other neurologic symptoms. These tumors may become evident either as a result of patient signs or symptoms or as an incidental finding on “baseline” neuroimaging studies. In an attempt to determine if there were differences between symptomatic and asymptomatic children with OPG, a retrospective cohort study of ninety children with NF1 and OPG was performed using data from two large NF1 referral centers. Age at diagnosis, presenting symptoms, tumor location, associated features, and clinical response were assessed for children who were initially symptomatic from their OPG (n = 51) and compared to similar data of asymptomatic children whose tumors were incidentally discovered by MRI (n = 39). There were no differences in age at presentation, tumor location, NF1‐associated symptoms, or clinical response between the groups. Initially symptomatic children were much more likely to require treatment (OR: 14.8, 95% CI [1.9–116.7]) than those with incidentally discovered, asymptomatic OPG. Although 36% of OPG were diagnosed in children over the age of 6 years, none received prior neuroimaging and only two children had previously normal eye examinations, suggesting that the vast majority of OPG in this group were longstanding, undiagnosed tumors. Based on these findings, we do not advocate “baseline” MRI in children with NF1, but strongly recommend that all children of the age 10 years and younger with NF1 have complete annual ophthalmologic evaluations. © 2003 Wiley‐Liss, Inc.
Retinochoroidal atrophy in two adult patients with Angelman syndrome
Authors: Rufa A. , Dotti M.T. , Orrico A. , Battisti C. , Carletto F. , Federico A.
Published: September 2003

We describe a new ocular finding, retinochoroidal atrophy (RCA), associated with optic disk paleness in two adult patients with Angelman syndrome (AS) due to maternal 15q11‐13 deletion. The ocular involvement described in children with AS consists iris and choroids hypopigmentation due to loss of function of one copy of P gene involved in maternal deletion. The loss of one copy of the same gene of paternal origin leads to a similar ocular phenotype as in Prader–Willi syndrome (PWS). However to our knowledge, RCA has never been described before in PWS, suggesting that other maternally expressed genes, particularly UBE3A, could be responsible for the retinal changes observed in the adult AS phenotype. Although, further investigations would be necessary to better understand the role of the UBE3A in the retina, the findings reported here should prompt a systematic ophthalmologic evaluation adult patients with AS in order to establish the real incidence of RCA and prevent further disability in these patients. © 2003 Wiley‐Liss, Inc.
Distinctive metaphyseal chondrodysplasia with severe distal radius and ulna involvement (upper extremity mesomelia) and normal height
Authors: Camera Andrea , Camera Gianni
Published: September 2003

Metaphyseal chondrodysplasias (MCD) are skeletal disorders characterized by metaphyseal irregularities and, usually, by short stature. In MCD, wide heterogeneity exists with regard to clinical and radiological changes. We report on a patient with clinical and radiological findings of MCD who had coxa valga and normal height with metaphyseal involvement of the long bones. The short radii and ulnae showed a very severe change in their distal metaphyses, leading to mesomelic shortening confined to the upper limbs. Hematological, ophthalmological, and hearing examinations were normal. This type of MCD appears to represent a yet undescribed syndrome. © 2003 Wiley‐Liss, Inc.
A familial contiguous gene deletion syndrome at Xp22.3 characterized by severe learning disabilities and ADHD
Authors: Boycott Kym M. , Parslow Malcolm I. , Ross Judith L. , Miller Ivan P. , Bech‐Hansen N. Torben , MacLeod Patrick M.
Published: September 2003

We describe a mother and two sons with a 6‐Mb terminal deletion of the short arm of the X chromosome. The breakpoint was localized to a region between DXS6837 and sAJ243947 in Xp22.33. The two boys were shown to be deleted for the SHOX and ARSE genes on their X chromosome. Both sons were short in stature and showed mild to moderate skeletal abnormalities. The most significant findings in the younger son were severe learning disabilities and attention deficit hyperactivity disorder (ADHD). The older son tested in the mild mental retardation range and was also affected by ADHD. The VCX‐A gene, implicated recently in X‐linked nonspecific mental retardation, was found to be present in both boys. The mother's stature was greater than one standard deviation below her target height and she had only subtle radiographic evidence of Madelung deformity. Our findings indicate that loss of the Xp22.3 region is not always associated with the classic presentations of Léri‐Weill syndrome, or chondrodysplasia punctata, and that one or more genes involved in learning and attention may reside in Xp22.3. © 2003 Wiley‐Liss, Inc.
Prenatal diagnosis of boomerang dysplasia
Authors: Wessels Marja W. , Den Hollander Nicolette S. , De Krijger Ronald R. , Bonifé Luisa , Superti‐Furga Andrea , Nikkels Peter G. , Willems Patrick J.
Published: September 2003

Boomerang dysplasia, atelosteogenesis type 1 and Piepkorn dysplasia are bone dysplasias with an overlapping clinical spectrum characterized by deficient formation and ossification of specific elements of the skeleton. Typical symptoms include micromelia with diminished ossification, and a characteristic bowed and boomerang‐like aspect of the long tubular bones. We report here a new case of boomerang dysplasia, which was detected prenatally in the 16th week of gestation by ultrasound. © 2003 Wiley‐Liss, Inc.
Subtle trisomy 12q24.3 and subtle monosomy 22q13.3: Three new cases and review
Authors: Rodríguez Laura , Guardia Nieves Martínez , Herens Christian , Jamar Mauricette , Verloes Alain , López Fermina , Mun̄oz José Santos , Martínez‐Frías María Luisa
Published: September 2003

The high resolution G‐bands (850 bands) karyotype have made it possible to identify small chromosome anomalies (5 megabases) which are now microscopically visible. New techniques have been improved, such as the Fluorescent in situ hybridization (FISH) with subtelomeric probes, which can be employed to detect cryptic chromosome alterations not visible microscopically. We present three cases which had been remitted for a high resolution karyotype. The high resolution G‐band karyotype and the FISH techniques led us to conclude that the three cases were carriers of a similar subtle chromosomal alteration. Case I is a new born female with developmental and psychomotor delay, hypotonia, and long limbs with arachnodactily. A high resolution G‐band karyotype showed an abnormal chromosome 22. FISH techniques confirmed a der(22)t(12;22)(q24.31;q13.3). Case II is a 12‐year‐old girl, with growth retardation, long shaped face with thick eyebrows, smooth philtrum, and thin upper lip with severe mental retardation (still no language), with a phenotype very similar to that of his sister: long shaped face, thick eyebrows, smooth philtrum, and thin upper lip. A high resolution G‐band karyotype also showed in Case II and III an abnormal chromosome 22, studied by FISH techniques which confirmed a der(22)t(12;22)(q24.3;q13.3) in both cases. © 2003 Wiley‐Liss, Inc.
Second reported patient with del(1)(p32.1p32.3) and similar clinical features suggesting a recognizable chromosomal syndrome
Authors: Zinner Samuel H. , Batanian Jacqueline R.
Published: September 2003

Interstitial deletion of the short arm of chromosome 1 is rare. Eleven different breakpoints have been described in 12 children. We report a patient with del(1)(p32.1p32.3). Only one of the previously reported patients had an apparent identical deletion to that of the present case. The phenotypes of the two patients are strikingly similar. Distinctive features include excessive weight gain during the first 30 months, macrocephaly, frontal bossing, rounded face, mild synophyrs, slightly upslanting eyes, short palpebral fissures, broad nasal bridge, low set ears, prominent philtrum, long eyelashes, and delayed psychomotor development. © 2003 Wiley‐Liss, Inc.
Gershoni–Baruch syndrome: Report of a new family confirming autosomal recessive inheritance
Authors: Franceschini P. , Guala A. , Licata D. , Botta G. , Flora F. , Angeli G. , Di Cara G. , Franceschini D.
Published: September 2003

Gershoni–Baruch syndrome is a multiple congenital malformation complex characterized by omphalocele, diaphragmatic hernia, cardiovascular abnormalities, and radial ray defects. Autosomal recessive inheritance is suggested. We describe two additional cases from a single family (sister and brother) delivered through termination at 23 and 9 weeks of gestation, respectively. The first fetus showed a spectrum of schisis defects without any limb involvement while the second bore mainly malformations of hands and feet. The occurrence of two different syndromes in the same family is highly improbable, but, considering both malformation complexes as possible manifestations of the same disease, a diagnosis of Gershoni–Baruch syndrome appears the most reasonable. These new familial cases bring further support to the hypothesis of an autosomal recessive inheritance of this syndrome. © 2003 Wiley‐Liss, Inc.
Deletion of the SLUG (SNAI2) gene results in human piebaldism
Authors: Sánchez‐Martín Manuel , Pérez‐Losada Jesús , Rodríguez‐García Arancha , González‐Sánchez Belén , Korf Bruce R. , Kuster W. , Moss Celia , Spritz Richard A. , Sánchez‐García I.
Published: September 2003

Slug is a zinc‐finger neural crest transcription factor, encoded by the SLUG gene, which is critical for development of hematopoietic stem cells, germ cells, and melanoblasts in the mouse. In mouse, heterozygous and homozygous slug mutations result in anemia, infertility, white forehead blaze, and depigmentation of the ventral body, tail, and feet. This phenotype is very similar to the heterozygous W (KIT)‐mutant mouse phenotype and to human piebaldism, which is characterized by a congenital depigmented patches and poliosis (white forelock). To investigate the possibility that some cases of human piebaldism might result from abnormalities of the human SLUG (SNAI2) gene, we carried out Southern blot analysis of the SLUG gene in 17 unrelated patients with piebaldism, who lack apparent KIT mutations. Three of these patients had evident heterozygous deletions of the SLUG gene encompassing the entire coding region. Real‐time PCR confirmed the deletion in all cases. Fluoresence in situ hybridization (FISH) of genomic SLUG probes to metaphase chromosomes independently confirmed the deletion in one of the cases. These findings indicate that some cases of human piebaldism result from mutation of the SLUG gene on chromosome 8, and provide further strong evidence for the role of SLUG in the development of human melanocytes. © 2003 Wiley‐Liss, Inc.
Schwann cell chemokine receptors mediate HIV‐1 gp120 toxicity to sensory neurons
Authors: Keswani Sanjay C. , Polley Michelle , Pardo Carlos A. , Griffin John W. , McArthur Justin C. , Hoke Ahmet
Published: September 2003

Human immunodeficiency virus (HIV)–associated sensory neuropathy (HIV‐SN) is the most common neurological complication of HIV infection. Currently, the pathogenesis of HIV‐SN is unknown. Because there is no convincing evidence of neuronal infection, HIV neurotoxicity is likely to be effected either by secreted viral proteins such as the envelope glycoprotein gp120 or by neurotoxic cytokines released from infected/activated glial cells. We describe a model of gp120 toxicity to primary sensory neurons, in which gp120 induces neuritic degeneration and neuronal apoptosis. We show that Schwann cells, the cells that ensheath peripheral nerve axons, and which traditionally have been viewed as having a passive, supporting role, mediate this neurotoxicity. Ligation of the chemokine receptor CXCR4 on Schwann cells by gp120 resulted in the release of RANTES, which induced dorsal root ganglion neurons to produce tumor necrosis factor–α and subsequent TNFR1‐mediated neurotoxicity in an autocrine fashion. This newly described Schwann cell–neuron interaction may be pathogenically relevant not only in HIV‐SN but also in other peripheral neuropathies. Ann Neurol 2003;54:287–296
Intraoperative infrared functional imaging of human brain
Authors: Gorbach Alexander M. , Heiss John , Kufta Conrad , Sato Susumo , Fedio Paul , Kammerer William A. , Solomon Jeffrey , Oldfield Edward H.
Published: September 2003

We hypothesized that it would be possible to detect the distribution of cortical activation by using a sensitive, rapid, high‐resolution infrared imaging technique to monitor changes in local cerebral blood flow induced by changes in focal cortical metabolism. In a prospective study, we recorded in 21 patients the emission of infrared radiation from the exposed human cerebral cortex at baseline, during language and motor tasks, and during stimulation of the contralateral median nerve using an infrared camera (sensitivity 0.02°C). The language and sensorimotor cortex was identified by standard mapping methods (cortical stimulation, median nerve somatosensory‐evoked potential, functional magnetic resonance imaging), which were compared with infrared functional localization. The temperature gradients measured during surgery are dominated by changes in local cerebral blood flow associated with evoked functional activation. The distribution of the evoked temperature changes overlaps with, but extends beyond, functional regions identified by standard mapping techniques. The distribution observed via infrared mapping is consistent with distributed and complex functional representation of the cerebral cortex, rather than the traditional concept of discrete functional loci demonstrated by brief cortical stimulation during surgery and by noninvasive functional imaging techniques. By providing information on the spatial and temporal patterns of sensory‐motor and language representation, infrared imaging may prove to be a useful approach to study brain function. Ann Neurol 2003
Speech production after stroke: The role of the right pars opercularis
Authors: Blank S. Catrin , Bird Helen , Turkheimer Federico , Wise Richard J. S.
Published: September 2003

Recovery of speech after infarction of the left pars opercularis (POp) may be due to recruitment of homotopic cortex in the right hemisphere. Using positron emission tomography, we investigated activity within left and right POp during everyday propositional speech. We studied seven aphasic patients with left anterior perisylvian infarction which included the POp. We compared their data with two control groups: 12 normal subjects and 7 anterior aphasic patients whose infarcts spared the left POp. During propositional speech, normal subjects activated the left POp, left posterior perisylvian cortex, and a distributed, predominantly left‐lateralized, extrasylvian neural network. Importantly, activity in the right POp was reduced relative to a baseline nonspeech condition. In patients with infarction of the left POp, activity in the right POp was reversed: speech activated the right POp above baseline. Patient controls activated the left POp but did not show the normal relative reduction in activity in the right POp. In both patient groups, posterior perisylvian and extrasylvian activations remained unchanged from normal. This result demonstrates that infarction of the left POp is associated with a chronic change in function of the contralateral homotopic cortex during speech. Ann Neurol 2003;54:000–000
Aphasia in hyperacute stroke: Language follows brain penumbra dynamics
Authors: Croquelois Alexandre , Wintermark Max , Reichhart Marc , Meuli Reto , Bogousslavsky Julien
Published: September 2003

During the first few hours after onset, stroke symptoms may evolve rapidly. We studied the correlation between brain perfusion and aphasia changes during the hyperacute phase of stroke using a new technique of perfusion computed tomography (P‐CT). Using an aphasia score developed for each language modality, language was evaluated within 6 hours after onset, then sequentially during the first week. Maps of the penumbra and infarct obtained from P‐CT images and definite infarct size evaluated using T2 and diffusion‐weighted MRI (DWI) on day 3 were rated by a neuroradiologist, blinded to the clinical deficit. Within 6 hours, deficits in all language modalities were present in 13 out of 24 consecutive patients, corresponding to large anterior‐posterior perfusion deficits of the left middle cerebral artery (MCA) territory. The aphasia score correlated with a corresponding perfusion deficit in specific areas of the MCA territory, and showed significantly less improvement when the penumbra evolved toward infarction than when at least part of the penumbra was rescued. Our findings suggest a particularly good correlation between the evolution of aphasic symptoms and penumbra dynamics. Further studies on the relevance of penumbra dynamics in function‐specific brain areas to decision taking in hyperacute stroke management are required.
Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia
Authors: Ginsberg Myron D. , Becker David A. , Busto Raul , Belayev Andrey , Zhang Yongbo , Khoutorova Larissa , Ley James J. , Zhao Weizhao , Belayev Ludmila
Published: September 2003

Azulenyl nitrones are novel chain‐breaking antioxidants with low oxidation potentials and high lipophilicity—properties favoring their efficacy as neuroprotectants. We tested the second‐generation azulenyl nitrone, stilbazunenlyl nitrone (STAZN), in focal ischemic stroke. Physiologically monitored rats received 2 hours of middle cerebral artery occlusion by intraluminal suture, resulting in substantial cortical and striatal infarcation. Neurobehavior was quantified on a standard battery, and brains were perfusion‐fixed for quantitative histopathology at 3 days. In 3 independent series, rats were treated at either 2h + 4h, or 2h + 4h + 24h + 48h, after onset of ischemia; vehicle‐treated rats received dimethylsulfoxide or saline. All animals (n = 52) developed high‐grade neurological deficits (score 11 of 12) during ischemia, which improved, in STAZN‐treated rats, within 1–1.5 h of the initial dose and fell to a median score of 3 at 72 h, compared to 8 in vehicle rats. STAZN treatment reduced mean cortical infarct volume by 64–97%, and total infarct volume by 42–72%. In over one‐half of STAZN‐treated animals, cortical infarction was virtually abolished. Regression analysis predicted that STAZN would confer ∼50% cortical neuroprotection even in the most severely affected cases. The potency of STAZN was orders‐of‐magnitude greater than other nitrones such as NXY‐059. These results suggest that STAZN has great promise for ischemic stroke. Ann Neurol 2003
Cerebral hemorrhage produced by ruptured dissecting aneurysm in miliary aneurysm
Authors: Rosenblum William I.
Published: September 2003

This report describes, for what may be only the second time, a ruptured miliary aneurysm within a cerebral hemorrhage. The report is unique in that the aneurysm has arisen at the site of a dissection within the wall of an arteriole at a site of fibrinoid necrosis. The case not only is a unique illustration of this pathogenetic pathway to miliary aneurysm formation, but also reemphasizes the relationship between fibrinoid and miliary aneurysm formation.
Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment
Authors: Nestor Peter J. , Fryer Tim D. , Smielewski Peter , Hodges John R.
Published: September 2003

The neural basis of the amnesia characterizing early Alzheimer's disease (AD) remains uncertain. Postmortem pathological studies have suggested early involvement of the mesial temporal lobe, whereas in vivo metabolic studies have shown hypometabolism of the posterior cingulate cortex. Using a technique that combined the anatomic precision of magnetic resonance imaging with positron emission tomography, we found severe reductions of metabolism throughout a network of limbic structures (the hippocampal complex, medial thalamus, mamillary bodies, and posterior cingulate) in patients with mild AD. We then studied a cohort with mild cognitive impairment in whom amnesia was the only cognitive abnormality and found comparable hypometabolism through the same network. The AD and mild cognitive impairment groups were differentiated, however, by changes outside this network, the former showing significant hypometabolism in amygdala and temporoparietal and frontal association cortex, whereas the latter did not. The amnesia of very early AD reflects severe but localized limbic dysfunction.
Matrix metalloproteinase–9 and spontaneous hemorrhage in an animal model of cerebral amyloid angiopathy
Authors: Lee Jin‐Moo , Yin Ke‐Jie , Hsin Idar , Chen Shawei , Fryer John D. , Holtzman David M. , Hsu Chung Y. , Xu Jian
Published: September 2003

We examined the potential role of the extra‐cellular matrix‐degrading enzyme, matrix metalloproteinase‐9 (MMP‐9), in the pathogenesis of cerebral amyloid angiopathy (CAA)‐induced spontaneous hemorrhage. The amyloid‐beta peptide (Aβ) induced the synthesis, release and activation of MMP‐9 in murine cerebral endothelial cells, resulting in increased extracellular matrix degradation. Furthermore, extensive MMP‐9 immunoreactivity was observed in CAA‐vessels with evidence of microhemorrhage in aged APPsw transgenic mice, but not detected in aged wild type or young APPsw mice. These results suggest that increased vascular MMP‐9 expression, stimulated by Aβ, may play a role in the pathogenesis of spontaneous intracerebral hemorrhage in patients with CAA. Ann Neurol 2003;54:000–000
Transfer of the von Hippel‐Lindau gene to neuronal progenitor cells in treatment for Parkinson's disease
Authors: Yamada Hitoshi , Dezawa Mari , Shimazu Seiichiro , Baba Masaya , Sawada Hajime , Kuroiwa Yoshiyuki , Yamamoto Isao , Kanno Hiroshi
Published: September 2003

Neuronal progenitor cells (NPCs) may provide dopaminergic neurons for the treatment of Parkinson's disease (PD). However, transplantation of NPCs into the striatum by current methods has had limited success. It is possible to reverse the symptoms of PD in model rats but difficult to reverse them in humans because the number of dopaminergic neurons generated from NPCs is low. We transduced the von Hippel–Lindau (VHL) gene into NPCs isolated from embryonic rat brain. The NPCs with the transduced VHL gene efficiently differentiated into tyrosine hydroxylase–positive neurons in vitro. NPCs with the transduced VHL gene, which were labeled in advance with bromodeoxyuridine, were transplanted into the striatum of a rat model of PD. Numerous bromodeoxyuridine–tyrosine hydroxylase double‐labeled cells were seen close to the transplant site, showing that the transplanted cells efficiently generated new dopaminergic neurons within the host striatum. Moreover, all of the animals with NPCs with VHL showed a remarkable decrease in apomorphine‐induced rotations. These findings show that NPCs with the VHL gene can efficiently generate dopaminergic neurons and that a sufficient number of dopaminergic neurons can develop from them to reverse the symptoms of PD in humans. VHL gene transduction provides a new therapeutic approach for treatment of PD. Ann Neurol 2003; 54:352–359