bluuebunny/crossref_metadata_2025 huggingface dataset:
Unique de novo interstitial deletion of chromosome 17, del(17) (q23.2q24.3) in a female newborn with multiple congenital anomalies
Authors: Levin Michael L. , Shaffer Lisa G. , Lewis Richard A. , Gresik Mary V. , Lupski James R.
Published: June 2005

We describe a newborn with a novel interstitial deletion of the long arm of chromosome 17 [del (17) (q23.2q24.3)] who died on day of life 17 during a recurrent apneic episode. Her phenotype included severe growth retardation, multiple facial anomalies, maldeveloped oralpharyngeal structures, and digital and widespread skeletal anomalies. This patient's phenotype was compared to two other reported patients with deletion 17q with minor clinical overlap consistent with a unique deletion. © 1995 Wiley‐Liss, Inc.
Some perinatal characteristics of monozygotic twins who are dichorionic
Authors: Machin Geoffrey , Bamforth Fiona , Innes Micheil , McNichol Kim
Published: June 2005

Zygosity testing of all multiple births allowed the identification of a subgroup of 42 monozygotic twin pairs who have dichorionic placentas, fused and separate. Perinatal outcomes of this group were compared with 110 pairs of monochorionic monozygotic twins and 148 pairs of dizygotic twins. Dichorionic monozygotic twins had the lowest incidence of preterm birth, perinatal mortality, and birth weight discordance.

There was an excess of like‐sexed over unlike‐sexed pairs among the dizygotic twins. © 1995 Wiley‐Liss, Inc.
Multi‐site neural tube closure in humans and maternal folate supplementation
Authors: Seller Mary J.
Published: June 2005

A group of 13 individuals with neural tube defects (NTD) despite maternal periconceptional folate supplementation was examined to determine precisely which closure sites along the neural tube had failed during embryogenesis. All the common forms of NTD, and thus all the usual closure sites, were represented. This suggests that folate deficiency does not act specifically on one region of the neural tube; rather, it may be more generally involved in the cause of human NTD. © 1995 Wiley‐Liss, Inc.
Chromosomal locations and modes of action of genes of the retinoid (vitamin A) system support their involvement in the etiology of schizophrenia
Authors: Goodman Ann B.
Published: June 2005

Vitamin A (retinoid), an essential nutrient for fetal and subsequent mammalian development, is involved in gene expression, cell differentiation, proliferation, migration, and death. Retinoic acid (RA) the morphogenic derivative of vitamin A is highly teratogenic. In humans retinoid excess or deficit can result in brain anomalies and psychosis. This review discusses chromosomal loci of genes that control the retinoid cascade in relation to some candidate genes in schizophrenia. The paper relates the knowledge about the transport, delivery, and action of retinoids to what is presently known about the pathology of schizophrenia, with particular reference to the dopamine hypothesis, neurotransmitters, the glutamate hypothesis, retinitis pigmentosa, dermatologic disorders, and craniofacial anomalies. © 1995 Wiley‐Liss, Inc.
Relationship of genetically transmitted alpha EEG traits to anxiety disorders and alcoholism
Authors: Enoch Mary‐Anne , Rohrbaugh John W. , Davis Elizabeth Z. , Harris Claudia R. , Ellingson Robert J. , Andreason Paul , Moore Veronica , Varner Jerald L. , Brown Gerald L. , Eckardt Michael J. , Goldman David
Published: June 2005

We tested the hypothesis that a heritable EEG trait, the low voltage alpha (LV), is associated with psychiatric disorders. Modest to moderate evidence for genetic linkage of both panic disorder and the low voltage alpha trait to the same region of chromosome 20q has recently been reported, raising the issue of whether there is a phenotypic correlation between these traits. A total of 124 subjects including 50 unrelated index subjects and 74 relatives were studied. Alpha EEG power was measured and EEG phenotypes were impressionistically classified. Subjects were psychiatrically interviewed using the SADS‐L and blind‐rated by RDC criteria. Alcoholics were four times more likely to be LV (including so‐called borderline low voltage alpha) than were nonalcoholic, nonanxious subjects. Alcoholics with anxiety disorder are 10 times more likely to be LV. However, alcoholics without anxiety disorder were similar to nonalcoholics in alpha power. An anxiety disorder (panic disorder, phobia, or generalized anxiety) was found in 14/17 LV subjects as compared to 34/101 of the rest of the sample (P < 0.01). Support for these observations was found in the unrelated index subjects in whom no traits would be shared by familial clustering. Lower alpha power in anxiety disorders was not state‐dependent, as indicated by the Spielberger Anxiety Scale. Familial covariance of alpha power was 0.25 (P < 0.01). These findings indicate there may be a shared factor underlying the transmissible low voltage alpha EEG variant and vulnerability to anxiety disorders with associated alcoholism. This factor is apparently not rare, because LV was found in approximately 10% of unrelated index subjects and 5% of subjects free of alcoholism and anxiety disorders. © 1995 Wiley‐Liss, Inc.
Prenatal diagnosis of FRA10A: A case report and literature review
Authors: Leon‐Luis Juan De , Santolaya‐Forgas Joaquin , May Gregory , Tonk Vijay , Shelton Doug , Galan Isabel
Published: June 2005

We report on the prenatal diagnosis of a familial fra10(q23)/del(10)(q23) detected after cellular cultures in non‐folic deprived medium. © 2005 Wiley‐Liss, Inc.
Development of an audit tool for genetic services
Authors: Skirton Heather , Parsons Evelyn , Ewings Paul
Published: June 2005

Rapid growth in demand and altered professional roles have produced changes in the delivery of genetic services over the past decade, but these have not been rigorously evaluated because of the paucity of appropriate audit tools. The aim of this study was to use clients' accounts and factor analysis to develop a robust assessment and audit tool. Qualitative data abstracted from several published studies were used to generate a number of statements related to outcomes of genetic services. A total of 57 statements were incorporated into a questionnaire. The questionnaire was mailed to clients of the Wales genetic service (n = 133) who had completed their episode of care. Respondents were asked to rank each statement on a seven‐point Likert type scale. Responses were subjected to factor analysis. A total of 97 anonymized responses were received (73% response rate). Six main factors were found to contribute to the outcome of the service from the client's perspective. These were labeled (i) enhanced understanding, (ii) positive psychological change, (iii) respect for autonomy, (iv) adaptation, (v) disequilibirium, and (vi) value of contact. The audit tool has now been refined for use in evaluating genetic services. Questions are included to investigate the six outcome areas shown to be relevant from the client's perspective. Data from the next phase of the study will be analyzed to validate the tool for use in both clinical audit and research contexts. © 2005 Wiley‐Liss, Inc.
Minor malformations characteristic of the retinoic acid embryopathy and other birth outcomes in children of women exposed to topical tretinoin during early pregnancy
Authors: Loureiro Kirsten D. , Kao Kelly K. , Jones Kenneth Lyons , Alvarado Sonia , Chavez Carmen , Dick Lyn , Felix Robert , Johnson Diana , Chambers Christina D.
Published: June 2005

Topical tretinoin (Retin‐A®) is used to treat acne and photodamaged skin. Its teratogenic potential is of concern due to its similarity to isotretinoin (Accutane®), a recognized human teratogen. Through the California Teratogen Information Service and Clinical Research Program, between 1983 and 2003, 106 pregnant women with first‐trimester exposure to topical tretinoin were prospectively ascertained and followed. Birth outcomes, including pregnancy loss, major structural defects, and pre‐ and postnatal growth were compared to 389 similarly and prospectively ascertained women with no topical tretinoin exposure during pregnancy. Because a distinct pattern of malformation had already been described for isotretinoin, we also compared exposed (n = 62) and unexposed (n = 191) infants on the prevalence of a specific subset of minor malformations selected to represent the spectrum of defects comprising the retinoic acid embyopathy. There were no significant differences between groups in the proportion of pregnancies ending in spontaneous abortion (6.6% in exposed vs. 8.5% in unexposed; P = 0.53), or infants with major structural defects (2.2% in exposed vs. 1.2% in unexposed; P = 0.62). In addition, the groups were similar in birth weight, length and head circumference, and there were no significant differences between groups in length of gestation. Furthermore, the prevalence of one or more retinoic acid‐specific minor malformations did not differ significantly between groups (12.9% in exposed vs. 9.9% in unexposed; P = 0.51). First‐trimester topical tretinoin exposure in this study was not associated with an increased risk of any adverse pregnancy outcome evaluated. Specifically, there was no indication that topical tretinoin is associated with an increased risk for minor malformations that are consistent with the retinoic acid embryopathy. Although it is impossible to exclude the possibility that some women/infants may be uniquely susceptible to topical tretinoin exposure, this study provides further reassurance for women who are inadvertently exposed early in pregnancy. © 2005 Wiley‐Liss, Inc.
Intrachromosomal triplication for the distal part of chromosome 15q
Authors: Schluth C. , Mattei M. G. , Mignon‐Ravix C. , Salman S. , Alembik Y. , Willig J. , Ginglinger E. , Jeandidier E.
Published: June 2005

We report the case of a boy whose karyotype at birth showed additional material on one chromosome 15. He underwent treatment for unilateral nephroblastoma at 6 years old. At 23 years old, he presented with body asymmetry, facial dysmorphism, arachnodactyly, severe scoliosis, and mental retardation. Molecular cytogenetic analyses of peripheral lymphocytes demonstrated a complex mosaic with three clones. A major cell lineage (68%) showed a chromosome 15 with additional material fused to its telomere long arm that was constituted by an inverted duplicated 15q24.3‐qter segment. Therefore, the resulting add(15)(q) harbored an intrachromosomal triplication with the middle segment being inverted in orientation. A minor cell lineage (7%) showed an abnormal chromosome 3 resulting from a telomeric fusion between its short arm and an inverted duplicated 15q24.3‐qter segment. The third cell lineage (25%) showed a normal 46,XY constitution. Finally, this resulted in tetrasomy for the distal 15q24.3‐qter region in 75% of the patient's lymphocytes. To our knowledge, distal 15q tetrasomy is rare and only eight cases have been reported in the literature, all due to a supernumerary analphoid marker consisting of an inverted duplication. We report here the first observation of distal 15q tetrasomy associated with a 46 chromosomes constitution. We compare the phenotype of our patient to previous cases of distal tetrasomy 15q and discuss the mechanisms underlying this chromosomal rearrangement. © 2005 Wiley‐Liss, Inc.
The adult phenotype in Costello syndrome
Authors: White Susan M. , Graham J.M. , Kerr B. , Gripp K. , Weksberg R. , Cytrynbaum C. , Reeder J.L. , Stewart F.J. , Edwards M. , Wilson M. , Bankier A.
Published: June 2005

We report clinical findings in 17 adults with Costello syndrome ranging in age from 16 to 40 years. Two patients in this series have had bladder carcinoma, the only malignancy reported to affect adults with Costello syndrome. Benign tumors included multiple ductal papillomata in two women, and a fourth ventricle mass in one man, thought to be a choroid plexus papilloma. Endocrine problems in this series were osteoporosis, central hypogonadism, and delayed puberty. Other health problems were symptomatic Chiari malformations in three patients. Four patients had adult‐onset gastro‐esophageal reflux, three of whom had Chiari malformations. Fourteen adults had mild to moderate intellectual disability with three individuals having severe intellectual disability; 15 individuals attained some reading and writing skills and 14 showed ongoing acquisition of new skills into adulthood. On the basis of this data, we recommend that neuro‐imaging be considered in adults with Costello syndrome if they develop symptoms suggestive of a Chiari malformation. In the event of pubertal delay, endocrine investigations are indicated and hormone treatment may be required. Bone density assessments should be performed in adults with Costello syndrome, particularly in those with pubertal abnormalities. Screening for microscopic hematuria as a marker for bladder carcinoma may be indicated, although this requires further evaluation. © 2005 Wiley‐Liss, Inc.
Reported multivitamin consumption and the occurrence of multiple congenital anomalies
Authors: Yuskiv Nataliya , Honein Margaret A. , Moore Cynthia A.
Published: June 2005

The purpose of this case‐control study was to determine whether multivitamin use is associated with the occurrence of multiple congenital anomalies (MCA). MCA case‐infants were infants with two or more major birth defects affecting at least two different organ systems, with no recognized chromosome abnormality or single gene disorder. Control‐infants were a random sample of live births with no major birth defects from the same population (metropolitan Atlanta) and time period (1993–1997) as the case‐infants. Exposure to multivitamins, cereals, and supplements was ascertained from a maternal telephone interview and classified based on folic acid content. We compared women who used multivitamins three or more times per week with women who were not exposed to vitamins/cereals/supplements during the periconceptional period (3 months before pregnancy through the first trimester), adjusting for maternal age, education, race/ethnicity, first degree family history of a major birth defect, pre‐pregnancy maternal body mass index, gravidity, and first trimester alcohol use and cigarette smoking. Periconceptional multivitamin use was associated with MCA among all infants (adjusted odds ratio [aOR] = 2.4, 95% confidence interval [CI] 0.9–6.7), and especially when analysis was limited to those with no family history of major defects (aOR = 4.0, 95% CI 1.3–12.8). MCA‐infants with urinary obstructive defects were more common among multivitamin‐exposed infants than among unexposed infants, but this defect did not occur within a consistent pattern of defects. While these findings provide some support for one previous study, the interpretation remains unclear given the proven protective effect of multivitamins containing folic acid on isolated neural tube defects and possibly other types of defects. Published 2005 Wiley‐Liss, Inc.
A new observation of acro‐cardio‐facial syndrome substantiates interindividual clinical variability
Authors: Mingarelli Rita , Zuccarello Daniela , Digilio Maria Cristina , Dallapiccola Bruno
Published: June 2005

We report on a baby presenting with ectrodactyly, heart defects, and mild facial dysmorphisms, an association recognized as acro‐cardio‐facial syndrome (ACFS). Based on the first three observations, the acronym CCGE, cleft palate, cardiac defect, genital anomalies, and ectrodactyly had been proposed to embrace the most consistent features of this syndrome. A subsequent report and the present patient point to an obvious interindividual and intrafamilial variability of this autosomal recessive disorder in which ectrodactyly was the sole characteristic shared by all affected individuals. © 2005 Wiley‐Liss, Inc.
Folate‐related genes and omphalocele
Authors: Mills James L. , Druschel Charlotte M. , Pangilinan Faith , Pass Kenneth , Cox Christopher , Seltzer Rebecca R. , Conley Mary R. , Brody Lawrence C.
Published: June 2005

Women who take folic acid in the periconceptional period greatly reduce their chances of having a child with a neural tube defect (NTD). Using multivitamins may also reduce the risk of having a child with an omphalocele. In this study, we tested single nucleotide polymorphisms in folate‐related enzyme genes for association with omphalocele. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase (MTHFD1), the reduced folate carrier (SLC19A1), and transcobalamin II (TCN2) were examined in 25 children with euploid omphalocele and 59 matched controls. Omphalocele cases were significantly more likely to carry the T allele of MTHFR 677C → T, a known risk factor for NTDs (odds ratio 3.50, 95% confidence interval 1.07–11.47, P = 0.035). The MTHFD1 R653Q, SLC19A1 R27H, and TCN2 P259R polymorphisms showed no significant association with omphalocele. In this small study, the thermolabile variant of MTHFR, 677C → T, was associated with an increased risk for omphalocele. This variant causes reduced enzyme activity, thus suggesting a mechanism by which multivitamins with folic acid might prevent omphalocele. Additional investigation is required. Published 2005 Wiley‐Liss, Inc.
Distinct phenotype associated with a cryptic subtelomeric deletion of 19p13.3‐pter
Authors: Archer H.L. , Gupta S. , Enoch S. , Thompson P. , Rowbottom A. , Chua I. , Warren S. , Johnson D. , Ledbetter D.H. , Lese‐Martin C. , Williams P. , Pilz D.T.
Published: June 2005

Telomeres are gene rich regions with a high recombination rate. Cryptic subtelomeric rearrangements are estimated to account for 5% of mental retardation/malformation syndromes. Here we present the first patient with a deletion of 19p13.3, identified by subtelomeric FISH analysis. His features included a distinctive facial appearance, cleft palate, hearing impairment, congenital heart malformation, keloid scarring, immune dysregulation, and mild learning difficulties. Subtelomeric FISH analysis identified a deletion of 19p13.3‐pter. The deletion size was determined to be 1.2 Mb by FISH analysis. It extended from within the chromosomal region covered by BAC RP11‐50C6 to 19pter. The deleted area encompassed approximately 60 genes. Fifteen possible candidate genes were considered with respect to the phenotype, including follistatin‐related precursor 3 (FSTL3) and serine‐threonine kinase 11 (STK‐11). © 2005 Wiley‐Liss, Inc.
Cause of sudden, unexpected death of Prader–Willi syndrome patients with or without growth hormone treatment
Authors: Nagai T. , Obata K. , Tonoki H. , Temma S. , Murakami N. , Katada Y. , Yoshino A. , Sakazume S. , Takahashi E. , Sakuta R. , Niikawa N.
Published: June 2005

Patients with Prader–Willi syndrome (PWS) are recognized to have a tendency of sudden, unexpected death (SED), but its exact cause is unknown because of paucity of such case reports. Since growth hormone (GH) treatment was applied to PWS patients worldwide, several cases of death have been reported. However, whether the therapy is directly related to their SED remains unknown, too. We collected 13 deceased PWS patients (Group A, aged 9 months to 34 years) who had never received GH therapy, and seven deceased patients (Group B, all boys aged 0.7–15 years) having received the therapy from the registration in PWS‐patient‐support associations and from the literature, respectively. We then compared the cause of SED between the two groups. Irrespective of GH therapy, SED of infants under age 1 year was associated with milk aspiration or hypothalamic dysregulation of respiration, while SED of patients in early childhood or adolescence occurred at sleeping in association with preceding viral infections. In contrast, SED of four adult (> 20 years of age) patients who never received GH therapy was associated with complications, such as leg cellulites and pulmonary embolism, secondary to massive obesity and diabetes mellitus (DM). Two Group‐B patients (aged 14 and 20 years) without any obesity‐related or diabetes‐related complications died of drowning in a bath tub, and their drowning death could be related to poor respiratory control. These findings indicated that the cause of SED is not essentially different between PWS patients with and without GH treatment. Deceased PWS patients may have had underlying respiratory dysregulation and hypothalamic dysfunction, and GH therapy might have led to certain obstructive respiratory disturbances that exacerbated the respiratory conditions. This will call clinicians' attention when using GH in PWS patients, for example, careful determination of the dose of GH and careful monitoring of patient's respiratory conditions, especially in male obese patients with respiratory problems. © 2005 Wiley‐Liss, Inc.
Molecular characterization of del(8)(p23.1p23.1) in a case of congenital diaphragmatic hernia
Authors: Shimokawa Osamu , Miyake Noriko , Yoshimura Takazumi , Sosonkina Nadiya , Harada Naoki , Mizuguchi Takeshi , Kondoh Shinji , Kishino Tatsuya , Ohta Tohru , Remco Visser , Takashima Takeshi , Kinoshita Akira , Yoshiura Koichiro , Niikawa Norio , Matsumoto Naomichi
Published: June 2005

A 36‐week‐old fetus was referred to the medical center because of his cystic mass and fluid in left thoracic cavity, and was delivered by cesarean section to manage neonatal problems at 37 weeks of gestation. Emergent surgical repair of the left diaphragmatic hernia was performed, but severe hypoxia persisted, and he expired on the following day. Chromosome analysis of cultured amniotic fluid cells indicated 46,XY,del(8)(p23.1p23.1). This is the fourth case of 8p23.1 deletion associated with diaphragmatic hernia. Microarray comparative genomic hybridization analysis using DNA of cultured amniotic fluid cells showed that six clones were deleted, which were mapped to the region between two low copy repeats (LCRs) at 8p23.1 previously described. Microsatellite analysis revealed that the deletion was of paternal origin, and his parents did not carry 8p23.1 polymorphic inversion. These data strongly suggested that the 8p23.1 interstitial deletion should have arisen through a different mechanism from that of inv dup del(8p) whose structural abnormality is always of maternal origin and accompanies heterozygous 8p23.1 polymorphic inversion in mother. © 2005 Wiley‐Liss, Inc.
Identification of an alternative 5′‐untranslated exon and new polymorphisms of angiotensin‐converting enzyme 2 gene: Lack of association with SARS in the Vietnamese population
Authors: Itoyama Satoru , Keicho Naoto , Hijikata Minako , Quy Tran , Phi Nguyen Chi , Long Hoang Thuy , Ha Le Dang , Ban Vo Van , Matsushita Ikumi , Yanai Hideki , Kirikae Fumiko , Kirikae Teruo , Kuratsuji Tadatoshi , Sasazuki Takehiko
Published: June 2005

We analyzed genetic variations of angiotensin‐converting enzyme 2 (ACE2), considering that it might influence patients' susceptibility to severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV) or development of SARS as a functional receptor. By cloning of the full‐length cDNA of the ACE2 gene in the lung, where replication occurs on SARS‐CoV, it was shown that there are different splicing sites. All exons including the new alternative exon, exon‐intron boundaries, and the corresponding 5′‐flanking region of the gene were investigated and 19 single nucleotide polymorphisms (SNPs) were found. Out of these, 13 SNPs including one non‐synonymous substitution and three 3′‐UTR polymorphisms were newly identified. A case control study involving 44 SARS cases, 16 anti‐SARS‐CoV antibody‐positive contacts, 87 antibody‐negative contacts, and 50 non‐contacts in Vietnam, failed to obtain any evidence that the ACE2 gene polymorphisms are involved in the disease process in the population. Nevertheless, identification of new 5′‐untranslated exon and new SNPs is considered helpful in investigating regulation of ACE2 gene expression in the future. © 2005 Wiley‐Liss, Inc.
Application of a comprehensive protocol for the identification of Gaucher disease in Brazil
Authors: Michelin Kristiane , Wajner Alessandro , de Souza Fernanda T.S. , de Mello Alexandre S. , Burin Maira G. , Pereira Maria Luiza S. , Pires Ricardo F. , Giugliani Roberto , Coelho Janice C.
Published: June 2005

Gaucher disease (GD) is a sphingolipidosis caused by a genetic defect that leads to glucocerebrosidase (β‐glucosidase) deficiency. Between January 1982 and October 2003, 1,081 blood samples from patients suspected of having GD were referred for biochemical analysis. The activities of the enzymes β‐glucosidase (β‐glu) and chitotriosidase (CT) were measured in these samples. Among the 412 diagnosed cases of GD (38.1%), the great majority were GD type 1. The Brazilian regions with the greatest concentration of these patients were the Southeast, South, and Northeast. The mean age of patients at diagnosis was 19 years. The activity of β‐glu in patients with GD was, on average, 10.7% of that of normal individuals. CT was, on average, 269 times more elevated in this group of patients. Among the 669 cases with no confirmation of GD, there were patients with Niemann–Pick disease types A, B, or C (44 cases), possible heterozygotes for GD (59 cases), patients with other lysosomal storage diseases (LSDs) (19 cases) or with other inborn errors of metabolism (3 cases). In 508 cases, no metabolic disorder was found. This study shows that the biochemical protocol employed was effective for the detection of GD, a disease that is reasonably frequent in Brazil. © 2005 Wiley‐Liss, Inc.
Detection of genomic rearrangements by DHPLC: A prospective study of 90 patients with inherited peripheral neuropathies associated with 17p11.2 rearrangements
Authors: Naïmi Mourad , Tardieu Sandrine , Depienne Christel , Ruberg Merle , Brice Alexis , Dubourg Odile , LeGuern Eric
Published: June 2005

Large genomic duplications and deletions are increasingly recognized as a cause of human disease. Charcot‐Marie‐Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP) result, respectively, from a duplication or deletion of a 1.5 Mb genomic region in 17p11.2‐12, containing the PMP22 gene. In routine diagnostic analysis, CMT1A status is inferred from the detection of an imbalanced dosage of two alleles or the presence of three alleles of a polymorphic marker flanking the PMP22 gene. HNPP is suspected if only one allele is seen, but hemizygosity must be confirmed by analyzing allele segregation in the family or by other techniques such as Southern blotting or fluorescence in situ hybridization (FISH). PCR‐based methodologies have also been developed that allow single‐step determination of the PMP22 gene copy number, wherein amplicons are typically labeled and/or separated by gel electrophoresis. We describe here a fast and reliable PCR‐based method for the diagnosis of CMT1A and HNPP in which the PMP22 gene is co‐amplified with a reference gene, and the amplicons are separated according to their size and quantified by DHPLC. Our results suggest that this method for quantifying gene dosage could be applied to other genomic rearrangements. © 2005 Wiley‐Liss, Inc.
A novel filamin A D203Y mutation in a female patient with otopalatodigital type 1 syndrome and extremely skewed X chromosome inactivation
Authors: Hidalgo‐Bravo Alberto , Pompa‐Mera Ericka N. , Kofman‐Alfaro Susana , Gonzalez‐Bonilla Cesar R. , Zenteno Juan Carlos
Published: June 2005

Otopalatodigital syndrome type 1 (OPD1) [OMIM 311300] is an X‐linked dominant multiple congenital anomalies disease mainly characterized by a generalized skeletal dysplasia, mild mental retardation, hearing loss, cleft palate, and typical facial anomalies. OPD1 belongs to a group of X‐linked skeletal dysplasias known as oto‐palato‐digital syndrome spectrum disorders that also include OPD2, Melnick–Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). Recently, it has been demonstrated that mutations in the gene encoding the cytoskeletal protein Filamin A (FLNA) are responsible for this group of clinically overlapping human syndromes. We present the phenotypic and molecular data of a sporadic female patient clinically diagnosed with an OPD1 syndrome who carried a novel FLNA point mutation resulting in an Asp203Tyr substitution in the actin‐binding domain of the protein. X‐inactivation analyses demonstrated an extremely skewed pattern towards her maternal chromosome. Our results add to the molecular spectrum of the oto‐palato‐digital related syndromes and contribute to the delineation of phenotype‐genotype correlation in this group of X‐linked skeletal disorders. © 2005 Wiley‐Liss, Inc.
Cerebellar vermis aplasia: Patient report and exclusion of the candidate genes EN2 and ZIC1
Authors: Titomanlio Luigi , Pierri Nicola Brunetti , Romano Alfonso , Imperati Floriana , Borrelli Melissa , Barletta Valentina , Diano Alvaro Antonio , Castaldo Imma , Santoro Lucio , Del Giudice Ennio
Published: June 2005

Cerebellar vermis aplasia (ACV, OMIM 117360) is a rare malformation of the cerebellum, with only few familial patients reported so far. Main clinical features of this rare disorder include floppiness and delayed milestones in early infancy, preceding mild cerebellar ataxia, non‐progressive clinical course, normal or slightly delayed intelligence, and occasional nystagmus. Neuroimaging reveals selective involvement of the cerebellum, which is prominent in the vermis. Because of the large preponderance of female patients, X‐linked dominant transmission was suggested by [Fenichel and Phillips (1989); Arch Neurol 46:582–583], and subsequent reports only concern female patients. Only one family with male‐to‐male transmission presenting with a generalized atrophy of the cerebellum rather than a more localized vermis aplasia has been reported so far. We report on a family in which father and son are affected by a mild form of ACV, thus confirming an autosomal mode of inheritance of the disease. Our patients showed a progressive improvement of their motor abilities, neurological examination of the father being actually normal except for a mild mental retardation. We also evaluated the potential role of two candidate genes, EN2 and ZIC1, responsible for abnormal cerebellar development in murine knock‐out models. However, molecular analysis failed to reveal any causative mutation in the coding sequence of the two genes in our patients. The understanding of the genetic basis of autosomal dominant ACV would allow a better classification of isolate cerebellar malformations and might permit to understand cell differentiation and migration in the developing central nervous system. © 2005 Wiley‐Liss, Inc.
Generalized arterial calcification of infancy: Different clinical courses in two affected siblings
Authors: Cheng Kun‐Shan , Chen Ming‐Ren , Ruf Nico , Lin Shuan‐Pei , Rutsch Frank
Published: June 2005

Generalized arterial calcification of infancy (GACI) is a rare autosomal recessive disease caused by mutations in ENPP1. Due to extensive calcification of the arterial media associated with intimal proliferation leading to vascular occlusion, most affected children die within the first 6 months of life. We report on two Taiwanese siblings with an identical genotype, but different clinical course. The male sibling developed heart failure and severe hypertension, and died at the age of 6 weeks despite of treatment with bisphosphonates, ACE inhibitors, and hydralazine. The subsequent female, who was monitored closely pre‐ and post‐natally, is having an uncomplicated clinical course up to the age of 1½ year now. There were similar characteristic sonographic and roentgenographic findings in both siblings in early infancy. In both siblings, the same compound heterozygous mutations (c.1025G > T [p.Gly342Val] and c.1112A > T [Tyr371Phe]) in ENPP1 were identified. Despite the same genotype and similar sonographic and radiographic features in early infancy, the phenotype of GACI can vary to a great extent within one family. © 2005 Wiley‐Liss, Inc.
Risks for severe mental retardation occurring in isolation and with other developmental disabilities
Authors: Jelliffe‐Pawlowski Laura L. , Shaw Gary M. , Nelson Verne , Harris John A.
Published: June 2005

Individual and maternal characteristics as potential risk factors for having severe mental retardation (SMR) occurring with and without cerebral palsy (CP), epilepsy, or a pervasive developmental disorder (PDD) were explored among a cohort of 119,404 children without Down syndrome born in the California Central Valley in 1992 and 1993. Unadjusted and adjusted relative risks (RRs) and their 95% confidence intervals (CIs) based on the Poisson distribution were used to estimate the risks associated with each individual and maternal factor studied for each SMR diagnostic category. The most notable increased risks for SMR occurring in isolation or with CP or epilepsy was for children born low‐birth‐weight or preterm who were at a substantially increased risk (RRs 2.6–9.9). In contrast, the risk of SMR occurring with a PDD was the greatest among males compared to females (RR = 3.4, 95% CI 1.5, 7.9), Blacks compared to Whites (RR = 5.1, 95% CI 1.7, 15.5), and Asians compared to Whites (RR = 3.9, 95% CI 1.3, 12.0). Etiologic heterogeneity when SMR occurs with a PDD was suggested. © 2005 Wiley‐Liss, Inc.
Hair whorls and handedness: Informative phenotypic markers in nonsyndromic cleft lip with or without cleft palate (NS CL/P) cases and their unaffected relatives
Authors: Scott Nicole M. , Weinberg Seth M. , Neiswanger Katherine , Brandon Carla A. , Marazita Mary L.
Published: June 2005

Cleft lip with or without cleft palate (CL/P) is a complex disorder with a range of phenotypic manifestations and a birth prevalence that varies by population (1/500–1/2,000). Investigators have postulated that CL/P cases may have abnormal brain development, citing structural brain differences, and cognitive impairments in affected individuals. Previously, increased levels of non‐right handedness (NRH), a marker for abnormal brain lateralization, have also been demonstrated in CL/P cases. Atypical hair whorls, more direct markers of altered brain development, may be related to NRH. To date, neither hair whorl patterns nor their relationship to NRH have been studied in a CL/P population. In the current study, we investigate the hypothesis that altered brain development is part of the phenotypic spectrum of NS CL/P by assessing NRH and atypical hair whorls in CL/P families. The study population included 49 nonsyndromic CL/P cases and 116 of their unaffected relatives; 21.8% of the study population was NRH compared to the 10% population estimate (P < 0.0001). Counter‐clockwise hair whorls (CCW) were found in 12.7% of all subjects compared to a population rate of 9.9 %. Of all subjects, 11% of the NRH individuals had CCW, which was similar to the frequency of CCW in right‐handed individuals. Approximately 80% of the whorls were placed on either the right or center of the scalp. No significant associations were found between the type of cleft and handedness, hair whorl rotation, or placement. These results suggest that certain phenotypic markers of abnormal brain development may comprise part of the extended phenotype of orofacial clefting. © 2005 Wiley‐Liss, Inc.
Mosaicism for an FMR1 gene deletion in a fragile X female
Authors: Fan Hongxin , Booker Jessica K. , McCandless Shawn E. , Shashi Vandana , Fleming Alison , Farber Rosann A.
Published: June 2005

Most cases of fragile X syndrome result from expansion of CGG repeats in the FMR1 gene; deletions and point mutations of FMR1 are much less common. Mosaicism for an FMR1 full mutation with a deletion or with a normal allele has been reported in fragile X males. Here we report on a fragile X female who is mosaic for an FMR1 full mutation and an intragenic deletion. The patient is a 4‐year‐old girl with developmental delay, autistic‐like behaviors, and significant speech and language abnormalities. Southern blotting demonstrated the presence of a methylated full mutation, a normal allele in methylated and unmethylated forms, and an additional fragment smaller than the normal methylated allele. This result indicates that the patient is mosaic for a full mutation and a deletion, in the presence of a normal allele. By DNA sequence analysis, we mapped the 5′ breakpoint 63/65 bp upstream from the CGG repeat region and the 3′ breakpoint 86/88 bp downstream of the CGG repeats within the FMR1 gene. The deletion removed 210 bp, including the entire CGG repeat region. The full mutation was inherited from a premutation in the patient's mother. The deletion, which remained methylated at the Eag I and Nru I sites, was probably derived from the full mutation allele. Mosaicism of this type is rare in females with a fragile X mutation but should be kept in mind in the interpretation of Southern blots. © 2005 Wiley‐Liss, Inc.
Color changes in the haircoat of patas monkeys (Erythrocebus patas)
Authors: Palmer A. E. , London W. T. , Brown R. L. , Rice J. M.
Published: June 2005

Caged patas monkeys were evaluated monthly to determine changes in the color of their hair during infancy, adolescence, pregnancy and lactation. From birth until 3 months of age the facial and anterior crown hairs were short, sparse, and completely black. The body fur was a fine, short, fawn‐colored hair mixed with longer black hairs which produced a black‐tipped effect. During the second 3 months of life the body fur and anterior crown fur became coarser, longer, and changed to a red‐brown color. The facial hairs thickened and became longer, but remained totally black. A thin line of black hairs outlined the brow and temple. The black chin hairs were gradually replaced by white from 7 to 24 months of age, and the upper lip hairs changed from black to white during the second year of life.

Color changes related to pregnancy and lactation were confined to the nosepatch, cheek, and browline hair. The nosepatch and cheek hair changed from black or grey to completely white, and the browline faded to the approximate color of the body fur. These changes began approximately at the end of the second trimester of pregnancy, maximized during the third month of lactation, began to darken 1 to 2 months later, and returned completely to the black, nonpregnant colors approximately 1 year postpartum. In one nonlactating female, the darkening was delayed until 500 days postpartum and in one female ovariectomized in the light color phase, the darkening was complete 200 days later.

The cause of these changes is believed to be hormonal, resulting from altered endocrine function during maturation and pregnancy, which may alter melanocyte stimulating hormone activity.
Adoption of infant howling monkeys (Alouatta palliata)
Authors: Clarke Margaret R. , Glander Kenneth E.
Published: June 2005

During 3 years of continuous field observations on mantled howlers (Alouatta palliata Gray) in Costa Rica we observed five infants without mothers in the main study group. Four of these infants solicited care and two were adopted (one permanently, one temporarily) by lactating females. The other two were carried but not adopted. The fifth neither solicited nor received care. An infant must solicit care to receive care, and female howlers apparently can suckle more than one infant at a time.
Laparoscopic evaluation of the reproductive organs and abdominal cavity content of the lowland gorilla
Authors: Wildt D. E. , Chakraborty P. K. , Cambre R. C. , Howard J. G. , Bush M.
Published: June 2005

Laparoscopy was used to examine the abdominal cavity and evaluate reproductive competence in six adult female gorillas which had not demonstrated copulatory activity within 12 months of examination. Blood samples were obtained on the day of laparoscopy and analyzed for serum estradiol‐17β and progesterone. The uterus and oviducts of each gorilla appeared morphologically normal and free of lesions. The ovaries of three animals contained anatomical evidence of activity as indicated by the presence of luteal scars and a prominent corpus hemorrhagicum, corpus luteum, or developing follicles. No visible luteal or follicular tissue was observed on the ovaries of three gorillas. In the eldest female (age, 22 years) the ovaries were flaccid in texture and demonstrated irregularities in ovarian surface integrity, similar to that observed in women during reproductive senescence. Serum concentrations of estradiol‐17β and progesterone on the day of laparoscopy corresponded with observed ovarian activity. All six females had extensive adhesions in the abdominal cavity exclusive of the reproductive organs. Numerous gut, omentum, and liver to peritoneum adhesions were observed. The results indicated that laparoscopy was a safe and effective method for evaluating anatomical competence in the gorilla. Uterine and ovarian integrity appeared morphologically normal, but only three of the six gorillas showed evidence of ongoing ovarian activity.
Brief report: Occurrence of anti‐resonance in the song of the siamang (Hylobates syndactylus)
Authors: Haimoff Elliott H.
Published: June 2005

The duetting behavior of siamangs (Hylobates syndactylus) has previously been observed as representing a complex, interactively organized, and standardized set of vocal features. Anti‐resonance in the bitonal screams of 15 males was observed. The sound energy of the fundamental frequency of the first note of these screams are absorbed, the result being a fundamental frequency which was virtually filtered out. The implications and consequences of such a rare phenomenon as anti‐resonance in the vocal behavior in gibbons is discussed.
Body composition in baboons: Evaluating a morphometric method
Authors: Rutenberg Gary W. , Coelho Anthony M. , Lewis Douglas S. , Carey K. Dee , McGill Henry C.
Published: June 2005

The objective of this study was to determine whether noninvasive morphometric measurements of olive baboons (Papio cynocephalus anubis) can reliably predict lean body mass and fat mass in this species. Crown‐rump length, triceps circumference, and skinfold measures at the neck, subscapular, suprailiac, and triceps sites were obtained prior to necropsy from 21 clinically normal infant baboons at 18 weeks of age and from 22 clinically normal adolescent baboons at 5 years of age. At necropsy, the lean body mass and body fat mass were measured using gravimetric methods. Pearson's correlations and regression analysis were used to test the relationship between direct measures of lean and fat mass obtained at necropsy with calculated estimates based on morphometric measures obtained prior to death. Our null hypothesis was that the morphometric measures (individually or in combination) were not related to direct measures of fat mass or lean mass. Non‐linear and multiple regression estimators, by age and gender, were derived and provided increased predictability. Our results indicate that (1) morphometric measures can accurately predict lean body mass in male and female baboons; (2) morphometric measures used to predict lean body mass change with age; (3) morphometric measures are strongly associated with body fat mass at 18 weeks of age but are not as strongly associated with body fat mass in 5‐year‐old baboons; (4) triceps circumference provides the best single indicator of lean body mass for both genders and age periods; (5) baboons are like humans in that adolescent females tend to accumulate body fat while males of the same age tend to develop lean mass; and (6) combinations of these morphometric measurements explain between 70% and 100% of the variability and can be used to estimate lean and fat mass in baboons.
Relations among whole blood serotonin and sex, age, diet, and social status in Macaca nemestrina
Authors: Bowden Douglas M. , Brammer Gary L. , Fredrickson Timm , Raleigh Michael J. , Dougherty Amy , Short Robert A. , Williams Darrell D.
Published: June 2005

Whole blood serotonin (WBS) determinations were made in 56 pigtailed macaques (Macaca nemestrina) with approximately equal numbers in three age groups: young‐adult (4–5 years), middle‐aged (13–14 years), and old (over 18 years). The animals were housed in ten living groups with one female and male of each age group in each living group. Half of the groups were fed a diet high in lipid, cholesterol, simple sugars, and sodium; the other half received a restricted diet. Three determinations per animal showed WBS levels to be stable at two times of day and at a 1‐week interval, and individual differences were stable over several months' time. The mean WBS concentrations in M. nemestrina were found to be considerably higher than those reported for other species. The mean levels in females were almost 25% higher than in males. No significant effects of age, diet, or dominance status were detected.
Pregnancy, gestation and parturition in free‐ranging tana river crested mangabeys (Cercocebus galeritus galeritus)
Authors: Kinnaird Margaret F.
Published: June 2005

Mean gestation for seven free‐ranging Tana River crested mangabeys (Cercocebus galeritus galeritus) is 180 days (SE = 4.49). All females showed postconception sexual swellings after the first 2 months of pregnancy, and two of the seven copulated with males at this time. One birth was observed; observations of a second infant began less than 1 hr after birth. Details of parturition are given, with responses of group members to the events. Adult and juvenile females showed more sustained interest in the new infants than adult or juvenile males.
Social relationships of immigrant and resident female mountain gorillas. I. Male‐female relationships
Authors: Watts David P.
Published: June 2005

Adult males are important social partners for all females in mountain gorilla social groups, but male‐female relationships can vary in association with variation in female residence status, male age and mating status, and relatedness. Such variation occurred in a large group observed over a 3‐year period. All females associated and interacted affiliatively relatively often with a young silverback with whom all mated. Long‐term resident females also did so with an old, non‐breeding male to whom most were related, but recent immigrants spent little time near him and had few non‐aggressive interactions with him. The old male made agonistic interventions to support relatives; interventions in female conflicts by the younger male tended to ameliorate competitive differentials that immigrants faced and may have helped him to retain them as mates. Males aggression toward females was common, most probably served as a mating tactic, and did not involve resource competition. Extensive grooming by an adolescent male suggests that males may also use affiliative behavior to develop mating relationships. Females may have competed for proximity with and social access to the younger silverback; competitive success could influence how well females and their offspring are protected by silver‐backs, but the extent of such competition was not clear. Large group size may have heightened differentiation of male‐female relationships and competition among females, but comparative data from smaller groups generally corroborate the findings from the large group. © 1992 Wiley‐Liss, Inc.
Proximate and ultimate influences on the regulation of mating in the great apes
Authors: Nadler Ronald D.
Published: June 2005

Laboratory research on the great apes has revealed similarities in the proximate regulation of sexual behavior by hormonal, social, and spatial variables but differences among the species in various sexual and reproductive characteristics. Laboratory research indicated that all three species of great ape exhibited heightened female sexual motivation during the midcycle, periovulatory phase of the menstrual cycle, consistent with an interpretation of estrus. All three species were also similar in terms of mating at other times in the cycle as a result, primarily, of male sexual initiative/agression. Field research on the sexual behavior and social organization of the great apes under natural conditions suggested that the species differences were related, in part, to the species' mating systems—that is, to differences in intermale competition and female choice at estrus. Consideration of both proximate and ultimate influences on behavioral regulation facilitates the separate objectives of research directed primarily toward one or the other type of influence. © 1995 Wiley‐Liss, Inc.