bluuebunny/crossref_metadata_2025 huggingface dataset:
New finding of Schinzel‐Giedion syndrome: A case with a malignant sacrococcygeal teratoma
Authors: Robin Nathaniel H. , Grace Kimberly , DeSouza Trevor G. , McDonald‐McGinn Donna , Zackai Elaine H.
Published: June 2005

We report on a boy with Schinzel‐Giedion syndrome (SGS) with a previously unreported manifestation, a malignant sacrococcygeal teratoma. This is the second case of SGS to have a malignancy, as one earlier case had a hepatoblastoma. We postulate that the occurrence of 2 uncommon embryonic tumors among these patients with a rare syndrome may mean that risk of malignancy may be a component of this syndrome. © 1993 Wiley‐Liss, Inc.
Pathogenesis of craniofacial and body wall malformations induced by ochratoxin A in mice
Authors: Wei Xin , Sulik Kathleen K.
Published: June 2005

Ochratoxin A (OA), a mycotoxin commonly found in soils and on moldy food such as cereal grains, is a potent teratogen. The present investigation was designed to examine the teratogenicity of OA administered acutely at early post‐implantation stages in mice, with particular emphasis on the pathogenetic basis of induced malformations. Maternal OA administration on gestational day (GD) 7 or 8 resulted in excessive cell death in selected cell populations. After a single dose of 2–4 mg/kg, excessive amounts of cell death was notable within 6 hours, and persisted to 36 hours post‐treatment. As observed in GD 14 or 18 fetuses, the spectrum of induced craniofacial malformations included exencephaly, midfacial clefting, cleft lip, as well as hypotelorism, and synophthalmia associated with holoprosencephaly. Body wall defects involved either the abdominal wall alone, or in combination with the thoracic wall, resulting in partial or complete exposure of the viscera. Potential mechanisms for OA‐induced selective cell killing are discussed. © 1993 Wiley‐Liss, Inc.
Limb body wall complex: A critical review and a nosological proposal
Authors: Russo Rosa , D'Armiento Maria , Angrisani Pasquale , Vecchione Raffaella
Published: June 2005

The analysis of the literature on limb body wall complex reveals a varied and rather confused spectrum of cases. However, we noticed the presence of at least 2 clearly distinguishable phenotypes. The first phenotype shows craniofacial defects and amniotic bands and/or adhesion; the second—without craniofacial defects—presents urogeniatal anomalies, anal atresia, and abdominal placental attachment, together with a persistence of the extra‐embryonic coelom.

We think these 2 phenotypes are the consequence of different pathogenetic mechanisms. The pathogenesis of the first type can be related to an early vascular disruption, while the pathogenesis of the second one is attributable to an intrinsic embryonal maldevelopment.

Eight cases of the second phenotype were identified and the pathological findings proving this maldevelopmental origin are described. © 1993 Wiley‐Liss, Inc.
SHORT syndrome and insulin resistance
Authors: Schwingshandl Josef , Mache Christoph J. , Rath Karl , Borkenstein Martin H.
Published: June 2005

We describe a further case of SHORT syndrome. This girl shows nearly all the typical manifestations reported in patients with SHORT syndrome. However, at 14 years she presented with non‐ketotic hyperglycemia. At 161/2 years, the diagnosis of diabetes mellitus secondary to severe insulin resistance was made by intravenous insulin challenge. Insulin resistant diabetes mellitus seems to be a new finding in SHORT syndrome, not previously described in this condition. © 1993 Wiley‐Liss, Inc.
Distinctive autosomal or X‐linked dominant syndrome of microcephaly, mild developmental delay, short stature, and distinctive face
Authors: Winter R. M.
Published: June 2005

We report on a mother and two sons with a syndrome of microcephaly, short stature, a distinctive face, broad thumbs and great toes, and mild developmental delay. There are similarities to the patients reported by Bawle and Horton [Am J Med Genet 33:382–384, 1989] and Evans [Clin Genet 39:178–180, 1991] but it is not certain whether the patients have the same condition. Inheritance could either be autosomal or X‐linked dominant. © 1993 Wiley‐Liss, Inc.
Clinical variability within Brachmann‐de Lange syndrome: A proposed classification system
Authors: van Allen Margot I. , Filippi Giorgio , Siegel‐Bartelt Jacqueline , Yong Siu‐Li , McGillivray Barbara , Zuker Ron M. , Smith Charles R. , Magee J. F. , Ritchie Susan , Toi Ants , Reynolds James F.
Published: June 2005

Seven patients, including two sibs, with the Brachmann‐de Lange syndrome (BDLS) are presented as representative of the different types of BDLS in a proposed classification system. Type I (“classic”) patients have the characteristic facial and skeletal changes of BDLS using the criteria in the diagnostic index of Preus and Rex. Type I is distinguished from the other subtypes by prenatal growth deficiency (< 2.5 S.D. below mean for gestation) becoming more severe postnatally (< 3.5 S.D. below the mean), moderate to profound psychomotor retardation, and major malformations which result in severe disability or death.

Type II (“mild”) BDLS patients have similar facial and minor skeletal abnormalities to those seen in type I; however, these changes may develop with time or may be partially expressed. Patients with type II BDLS are distinguished from those with other types by mild to borderline psychomotor retardation, less severe pre‐and postnatal growth deficiency, and the absence of (or loss severe) major malformations. Behavioral problems can be a significant clinical problem in type II BDLS.

Type III (“phenocopies”) BDLS includes patients who have phenotypic manifestations of BDLS which are causally related to chromosomal aneuploidies or teratogenic exposures. © 1993 Wiley‐Liss, Inc.
Mild Brachmann‐de Lange syndrome. Delineation of the clinical phenotype, and characteristic behaviors in a six‐year‐old boy
Authors: Bay Carolyn , Mauk Joyce , Radcliffe Jerilynn , Kaplan Paige
Published: June 2005

Brachmann‐de Lange syndrome (BDLS) is a rare/multiple congenital anomaly/mental retardation (MCA/MR) syndrome with variable expression, making diagnosis of mild cases difficult. The most consistent manifestations appear to be the characteristic face, which can be subtle in children who are mildly affected [Ireland and Burn, 1991: Twelfth Annual David W. Smith Workshop on Malformations and Morphogenesis]. Other aspects of the syndrome include variable degrees of mental retardation, growth retardation, structural abnormalities of the limbs, and behavior abnormalities, noted to be “autistic” [Jones, 1988: “Smith's recognizable patterns of human malformation”]. Johnson et al. [1976: Pediatr Res 10:843–850] described a behavior phenotype felt to be common in patients with BDLS. They predicted that patients with BDLS may respond to “behavioral intervention”. Other behavior abnormalities in BDLS have been reported [Barr et al., 1971: Neurop̈adiatrie 3:46–66; Hawley et al., 1985: Am J Med Genet 20:453–459].

We report on a 6‐year‐old boy with the facial characteristics of BDLS, normal birth weight, prenatal onset of a small head relative to length, postnatal onset growth deficiency, nearly normal psychomotor development with onset of clear developmental delays by 2 years. He developed behavior problems similar to those seen in other patients with BDLS. These behaviors are most consistent with Pervasive Development Disorder‐NOS (PDD), and Autistic Disorder [DSM‐III‐R, 1987] which encompasses a spectrum of mild to severe autistic behaviors. We report successful in‐patient care utilizing medical and behavioral techniques to reduce the frequency of the behaviors. We feel that the presence of the characteristic behaviors may be helpful in confirming the diagnosis of BDLS. © 1993 Wiley‐Liss, Inc.
Brachmann‐de Lange syndrome: Diagnostic difficulties posed by the mild phenotype
Authors: Saul Rebert A. , Rogers R. Curtis , Phelan Mary C. , Stevenson Roger E.
Published: June 2005

We described 4 patients with facial changes of Brachmann‐de Lange syndrome but without limb defects. Mental retardation ranged from moderate to severe and the degree of Prenatal and postnatal growth deficiency was variable. These patients exemplify the diagnostic difficulties and counseling dilemmas posed by the mild Brachmann‐de Lange phenotype. The relationship of the mild phenotype to the full syndrome will not be understood until the pathogenetic or causal factor(s) are delineated. © 1993 Wiley‐Liss, Inc.
Radiological features in Brachmann‐de Lange syndrome
Authors: Braddock Stephen R. , Lachman Ralph S. , Stoppenhagen Cathy Charman , Carey John C. , Ireland Maggie , Moeschler John B. , Cunniff Christopher , Graham John M.
Published: June 2005

Brachmann‐de Lange syndrome (BDLS) is a well‐delineated disorder consisting variably of pre‐ and postnatal growth deficiency, microbrachycephaly, characteristic face, hypertrichosis, visceral anomalies, and limb defects consisting primarily of variable limb reduction defects, micromelia, and elbow abnormalities. The course is usually marked by initial hypertonicity, low‐pitched weak cry, feeding problems, and behavioral problems with marked mental deficiency. In classical cases there is rarely any difficulty in making the diagnosis but for mildly affected cases, it may be difficult to feel secure about the diagnosis. In an effort to increase the precision of diagnosis for mildly affected cases, we reviewed roentgenograms in 21 cases of Brachmann‐de Lange syndrome, as well as previously published descriptions of the radiological manifestations. Unusual radiologic manifestations were related primarily to the limb anomalies, and these were often asymmetric. These manifestations included digital abnormalities, which ranged from acheiria to oligodactyly, hypoplasia of the thumb and first metacarpal, clinodactyly of the fifth finger, or ectrodactyly. Long bone abnormalities included ulnar a/hypoplasia, dysplasia of the radial head, or fusion of the elbow. When there was a single forearm bone, there was often fusion at the elbow and oligodactyly, which made it difficult to determine whether the radius or ulna was absent. Other radiologic manifestations included 13 ribs with precocious sternal fusion, and micrognathia. We suggest that these radiologic manifestations could increase diagnostic precision in mildly affected cases. © 1993 Wiley‐Liss, Inc.
Occurrence of the Sandifer complex in the Brachmann‐de Lange syndrome
Authors: Sommer Annemarie
Published: June 2005

Gastroesophageal reflux is a common occurrence in infancy. The most severe complications of reflux include torticollis, opisthotonus, and paroxysmal dystonic posture (known as rhe Sandifer complex). We examined 17 patients now ranging in age from 9 months to 19 years (mean age 11 years) with the Brachmann‐de Lange syndrome for evidence of gastroesophageal reflux and found that 13 had not only reflux, but also posturing and behavior consistent with the Sandifer complex. We propose that early recognition of gastroesophageal reflux in these patients may prevent the full picture of the Sandifer complex and allow for medical treatment rather than surgical intervention. © 1993 Wiley‐Liss, Inc.
Growth manifestations in the Brachmann‐de Lange syndrome
Authors: Kline Antonie D. , Barr Marie , Jackson Laird G.
Published: June 2005

We have obtained serial measurements on 180 patients with clinically confirmed Brachmann‐de Lange syndrome (BDLS) in order to derive standard growth curves. The patients were evaluated in our genetics department and through meetings of the Cornelia de Lange Syndrome Foundation, a support group for families of affected individuals. The data were obtained from the records of pediatricians, other physicians, schools and parents, as well as from personal examination on each of these patients at least once, often periodically. The growth curves include height, weight and head circumference measurements from birth through adulthood. Prenatal growth and birth weights are below the 5th centile in most (68%) cases, with an average birth weight of 2,277 g. Growth persists below the normal curves in most of the patients throughout life. Height velocity is equal to the normal range but there is slower pubertal growth. Weight velocity is below the normal range throughout life until late adolescence. Average head circumference remains below the second centile. Thin body habitus coupled with slow growth and proportionate small stature is a manifestation of the syndrome, but is commonly mistaken for failure to thrive. © 1993 Wiley‐Liss, Inc.
Physical growth in Brachmann‐de Lange syndrome
Authors: Kousseff Boris G. , Thomson‐Meares Joanne , Newkirk Patricia , Root Allen W.
Published: June 2005

Growth in 30 patients with Brachmann‐de Lange syndrome (BDLS) was evaluated and found to be deficient in 27/30, with 17/27 having intrauterine growth retardation (IUGR). In 12/27 Patients, endocrine evaluations have been completed. Seven of 12 were normal and 4/12, one with empty sella, had “classical” growth hormone deficiency with extreme short stature, markedly delayed skeletal maturation and subnormal growth hormone secretion in response to provocative stimuli. One of 12 patients had discordance between insulin growth factor I levels and growth hormone responses to insulin and clonidine suggestive of end organ resistance to growth harmone. It appears that the hypothalmamic‐pituitary function is compromised in at least some BDLS patients. Thus, endocrine evaluations are warranted for the patients with short stature. © 1993 Wiley‐Liss, Inc.
Autopsy findings in a severely affected infant with a 2q terminal deletion
Authors: Waters Brenda L. , Allen Elizabeth F. , Gibson Pamela C. , Johnston Troy
Published: June 2005

We describe a 37‐week gestation female infant who was born with a terminal 2q deletion. Both of her parents had normal chromosomes. This infant had multiple anomalies, including hypertelorism, short palpebral fissures, microphthalmia, cleft lip/cleft palate, and abnormal ears. Autopsy documented Dandy‐Walker malformation with severe hydrocephalus, aortopulmonary window, secundum atrial septal defect, duodenal atresia, incomplete rotation of the bowel, gonadal dysgenesis, uterus didelphys, and musculoskeletal defects. Compared with the other 6 children with 2q terminal deletion documented in the literature, this patient is the most severely affected. This patient is also the only one documented to have died and undergone autopsy examination. The findings in this case provide more data for the eventual description of a “terminal 2q deletion syndrome” and suggest that some abnormalities, such as gonadal dysgenesis, may be present in living children with this chromosome abnormality. © 1993 Wiley‐Liss, Inc.
Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) associated with interstitial deletion of band 3q22: Review and gene assignment to the interface of band 3q22.3 and 3q23
Authors: Jewett Tamison , Rao P. Nagesh , Weaver R. Grey , Stewart William , Thomas Ioan T. , Pettenati Mark J.
Published: June 2005

We report on a child with blepharophimosis, ptosis, and epicanthus inversus (BPES), developmental delay and an interstitial deletion of band q22 of chromosome 3. A review of chromosome 3q anomalies associated with eye abnormalities, specifically blepharophimosis and ptosis, strongly suggests that a locus for eyelid development is present at the interface of bands 3q22.3 and 3q23. © 1993 Wiley‐Liss, Inc.
Banding resolution of human chromosomes: A method of accuracy and simplicity
Authors: Welbor Jeanna L. , Welborn Roger
Published: June 2005

Methods of estimationg chromosome band reolution have been published but their accuracy has not been established Banding resolution was determined by 4 methods which included a computerized linear correlation, the sum of bands on chromosomes 1 and 2, interpolation of the number of bands on chromosome 10, and interpolation of the number of bands on chromosomes 1p, 10 11p, 12q, and X. The sum of bands on chomosomes 1 and 2 multiplied by 6 is the most accurate and simple. The use of a simple and reliable method is important for cytogenetic laboratories to document quality assurance of routine chromosome analyses, to enhance the exchange of information between laboratories, and to establish criteria for appropriate band resolution for specific types of specimens. © 1993 Wiley‐Liss, Inc.
Oral involvement of recessive dystrophic epidermolysis bullosa inversa
Authors: Wright J. Timothy , Fine Jo‐David , Johnson Loraine B. , Steinmetz Todd T.
Published: June 2005

The inversa subtype of autosomal recessive dystrophic epidermolysis bullosa (EBDR‐I) is a rare variant characterized by lesions involving primarily the flexural areas of the body. The purpose of this investigation was to characterize the oral manifestations of this unusual dermatologic condition. Ten individuals having EBDR‐I were evaluated and compared with an age and sex‐matched population of unaffected individuals that served as controls. The diagnosis of EBDR‐I was confirmed by skin biopsy that demonstrated tissue separation below the lamina densa and the clinical presentation of blister formation that typically localized to flexural areas. There was clinical variability in the severity and distribution of skin involvement; however, none of the affected individuals demonstrated pronounced digital webbing, severe generalized blistering or growth retardation characteristic of the Hallopeau‐Siemens form of EBDR. Oral involvement was seen in all cases with ankyloglossia, loss of tongue papillae and obliteration of the oral vestibule between the lips and gingiva being typical. The oral opening was significantly reduced in older EBDR‐I individuals compared with matched controls, conforming that acquired microstomia is a charactorstic of EBDR‐I. The teeth were not clinically abnormal or malformed and showed no evidence of generalized enamel hypoplasia. Despite this, the prevalence of dental caries in EBDR‐I individuals was significantly higher than the control group. The inversa form of EBDR presents with oral findings that are similar but generally milder than those seen in the Hallopeau‐Siemens variant of EBDR. © 1993 Wiley‐Liss, Inc.
Presymptomatic DNA‐testing for Huntington disease: Pretest attitudes and expectations of applicants and their partners in the Dutch program
Authors: Tibben Aad , Frets Petra G. , van de Kamp Jacques J. P. , Niermeijer Martinus F. , Vegter‐van der Vlis Maria , Roos Raymund A. C. , van Ommen Gert‐Jan B. , Duivenvoorden Hugo J. , Verhage Frans
Published: June 2005

We studied the baseline attitudes, prior to testing, of 70 applicants at risk for Huntington disease (HD) and their partners in the Dutch presymptomatic DNA‐testing program. Two thirds of the applicants were female; 36% already had children. The main reason (60%) for undertaking the test was for family planning. Other reasons were either to reduce uncertainty (43%) or to obtain certainty (38%). Partners of applicants stated that planning for the future was for them the most important reason (76%). Significantly more at‐risk females (42%) than males (16%) anticipated an unfavorable test outcome. Quite remarkably, most applicants and partners denied that a positive result might have adverse effects on either personal mood, quality of life, or marriage. Only a few did not expect that a favorable result would induce relief. The eventual outcome of the test was expected to enable applicants to gain control over their future, whatever the result. Hence, we propose that the applicants form a self‐selected group, based on their expectation that they will not be emotionally affected by either result. © 1993 Wiley‐Liss, Inc.
Legal and ethical issues in psychiatric genetic research
Authors: Shore David , Berg Kate , Wynne Debra , Folstein Marshal F.
Published: June 2005

Genetic research may uncover the causes of severe mental disorders, and many projects have been undertaken to locate the genes responsible for schizophrenia, bipolar disorder, and Alzheimer disease. A number of sensitive legal and ethical issues have been raised, including 1) protection of confidential data concerning research subjects; 2) the assessment of types and degree of risk to subjects who participate in such studies; 3) the legal and ethical acceptability of substituted judgment on behalf of patients who may not be competent to provide informed consent; and 4) the separation of research and clinical roles in areas such as genetic counseling. Federal regulations and other guidelines are of limited value in dealing with such concerns, and many important human subjects issues will need to be dealt with by the investigator, subject to approval by a local Institutional Review Board. There does seem to be general agreement that informed consent must be obtained, potential risks of research need to be minimized, and confidentiality of sensitive data must be protected. © 1993 Wiley‐Liss, Inc.
Novel association approach for determining the genetic predisposition to schizophrenia: Case‐control resource and testing of a candidate gene
Authors: Sobell Janet L. , Heston Leonard L. , Sommer Steve S.
Published: June 2005

We have developed a two‐tiered approach to elucidating the genetic predisposition to schizophrenia. The approach first involves the examination of candidate genes in a subset of schizophrenic individuals to identify DNA sequence variations of likely functional significance, i.e., that produce either structural alterations in the protein or affect the level of gene expression. Once identified, the prevalence of the aberrant allele is examined in a large group of unrelated schizophrenic cases and controls to assess whether a true disease association exists. Herein, we describe the establishment of a DNA bank on nearly 200 unrelated schizophrenic cases defined by DSM‐III‐R criteria and on over 300 unrelated, ethnically similar controls. Characteristics of the study sample are described. The study approach then is illustrated by testing known mutations in the phenylalanine hydroxylase gene, responsible for the autosomal recessive disease of phenylketonuria, in the case‐control sample to determine if carriership of a mutant allele is associated with an increased risk of schizophrenia. Using PCR amplification of specific alleles (PASA), we screened 190 schizophrenic cases and 336 controls for two common point mutations in the phenylalanine hydroxylase gene. Two carriers were found among the controls, while none of the cases was shown to carry a mutant allele. Thus, carriership of either of two common mutations in the phenylalanine hydroxylase gene does not appear to be associated with an increased risk of schizophrenia. As additional candidate genes are tested in this case‐control resource, adjustment for multiple comparisons will become crucial in order to reduce the chance of false positive findings. The ascertainment of auxillary groups of cases and controls with sequential hypothesis testing in these groups offers a technically feasible solution to the multiple comparisons problem. © 1993 Wiley‐Liss, Inc.
Linkage of familial alzheimer disease to chromosome 14 in two large early‐onset pedigrees: Effects of marker allele frequencies on lod scores
Authors: Nechiporuk A. , Fain P. , Kort E. , Nee L. E. , Frommelt E. , Polinsky R. J. , Korenberg J. R. , Pulst S‐M.
Published: June 2005

Alzheimer disease (AD) is a devastating neurodegenerative disease leading to global dementia. In addition to sporadic forms of AD, familial forms (FAD) have been recognized. Mutations in the amyloid precursor protein (APP) gene on chromosome (CHR) 21 have been shown to cause early‐onset AD in a small number of pedigrees. Recently, linkage to markers on CHR 14 has been established in several early‐onset FAD pedigrees. We now report lod scores for CHR 14 markers in two large early‐onset FAD pedigrees. Pairwise linkage analysis suggested that in these pedigrees the mutation is tightly linked to the loci D14S43 and D14S53. However, assumptions regarding marker allele frequencies had a major and often unpredictable effect on calculated lod scores. Therefore, caution needs to be exercised when single pedigrees are analyzed with marker allele frequencies determined from the literature or from a pool of spouses. © 1993 Wiley‐Liss, Inc.
Candidate genes in psychiatry: An epidemiological perspective
Authors: Crowe Raymond R.
Published: June 2005

Interest in candidate genes in psychiatry has been revived by the success of that approach in Alzheimer's disease as well as by discouragement over the results to date of searches for linkage. If mutations in candidate genes could be detected directly many of the complexities of searching for them indirectly through linkage could be avoided. As attractive as this approach may sound, mutation searches with candidate genes will introduce a new set of difficulties: the large number and low a priori probability of potential candidate genes virtually guarantees that most positive findings will be false positives. Consequently, if candidate genes are to be systematically studied, procedures need to be established for minimizing and efficiently disconfirming false positive results. © 1993 Wiley‐Liss, Inc.
No association between schizophrenia and homozygosity at the D3 dopamine receptor gene
Authors: Yang Liu , Li Tao , Wiese Claudia , Lannfelt Lars , Sokoloff Pierre , Xu Chong T. , Zeng Zhong , Schwartz Jean‐Charles , Liu Xiehe , Moises Hans W.
Published: June 2005

The D3 dopamine receptor gene is an important candidate gene for schizophrenia, since (because of its almost exclusive expression in the limbic system) it combines the dopamine receptor hypothesis with the limbic system hypothesis of schizophrenia. A BalI restriction fragment length polymorphism of the D3 dopamine receptor gene has been typed in 107 schizophrenic patients and 98 normal controls from Sichuan (China). With regard to alleles or genotypes, no significant differences were obtained between controls from Europe and China, between patients and controls, and between patient subgroups and controls. These results indicate a lack of association between schizophrenia and the D3 dopamine receptor gene in our sample. Our findings are at variance with reports of a significant excess of homozygosity at the D3 dopamine receptor gene in schizophrenic patients from Wales (United Kingdom) and Alsace (France). In conclusion, further studies will be needed with larger samples of patients from Wales and Alsace as well as with samples of different racial groups to prove or disprove the initial positive association between schizophrenia and genotypes of the D3 dopamine receptor gene. © 1993 Wiley‐Liss, Inc.
Lack of association between bipolar affective disorder and tyrosine hydroxylase DNA marker
Authors: Inayama Yasuhiro , Yoneda Hiroshi , Sakai Toshiaki , Ishida Toru , Kobayashi Shin‐Ichi , Nonomura Yasuhiro , Kono Yoshihiro , Koh Jun , Asaba Hiroyuki
Published: June 2005

Sixty‐eight patients with bipolar affective disorder and 88 controls were investigated for genetic association of tyrosine hydroxylase (TH) restriction fragment length polymorphisms (RFLPs). No significant association between bipolar affective disorder and TH was found. Thus the hypothesis that TH is involved in the pathogenesis of bipolar affective disorder was not supported. © 1993 Wiley‐Liss, Inc.
Dopamine D4 receptor variants in unrelated schizophrenic cases and controls
Authors: Sommer Steve S. , Lind Tammy J. , Heston Leonard L. , Sobell Janet L.
Published: June 2005

The D4 dopamine receptor (D4DR) exists in multiple allelic forms (Van Tol et al.: Nature 358:149–152, 1992) which involve different numbers of a 48 basepair repeat sequence in the putative third cytoplasmic loop. Different binding properties have been reported for at least three of the alleles in cDNA binding assays with clozapine, an atypical neuroleptic, and spiperone (Van Tol et al., 1992). We have examined 115 unrelated schizophrenic cases defined by DSM‐III‐R criteria and 115 controls of similar ethnicity to determine the frequency of seven different D4 alleles in these groups. No statistically significant difference in the distribution of the alleles existed between cases and controls, although a trend towards a greater prevalence of homozygotes for the 4‐repeat allele was observed in schizophrenics. © 1993 Wiley‐Liss, Inc.
Power to detect linkage with heterogeneity in samples of small nuclear families
Authors: Levinson Douglas F.
Published: June 2005

Computer simulation methods were used to investigate the power of genetically homogeneous or heterogeneous samples of nuclear families to detect linkage of a rare dominant disease allele to flanking DNA markers (threepoint analysis, admixture text). Phase was assumed to be unknown (no grandparents available), and unaffected siblings were not considered. A sample of 95 families with an ill parent and two ill offspring, or 45 families with three ill offspring, demonstrated 90% power to detect a lod score of 3.0 when 50% of families were assumed to be segregating for a disease allele located midway between two DNA markers (PIC = .70) that were .05 M apart. When the proportion of linked families (α) = .25, 90% power required 380 and 160 families, respectively. For α < .25, sample size requirements become prohibitive. Issues are reviewed concerning the use of the admixture test in the case of more complex disease models. Screening of the genome with adequate sample sizes for low values of α is likely to require multiple large collaborative efforts. © 1993 Wiley‐Liss, Inc.
Linkage between tyrosine hydroxylase gene and affective disorder cannot be excluded in two of six pedigrees
Authors: Lim Lionel C. C. , Gurling Hugh , Curtis David , Brynjolfsson Jon , Petursson Hannes , Gill Michael
Published: June 2005

Genetic linkage between manic depression and DNA markers on the short arm of chromosome 11 was first reported in 1987 but not supported by further analyses. However, genetic markers at the tyrosine hydroxylase (TH) gene located within this region have been reported to show allelic association with the affective disorder phenotype. We present the results of a linkage analysis using polymorphic DNA segments within the TH gene and the nearby dopamine D4 receptor (DRD4) gene in 6 families multiply affected with affective disorder. Small positive Lod scores were obtained in 2 of 6 pedigrees with the TH polymorphism which may be indicative of genetic heterogeneity. © 1993 Wiley‐Liss, Inc.
Risk factors for suicide in huntingtons disease: A retrospective case controlled study
Authors: Lipe Hillary , Schultz Amelia , Bird Thomas D.
Published: June 2005

We reviewed 11 instances of suicide in HD families to determine what clinical and social characteristics might alert health professionals to increased suicide potential. The subjects were eight males and one female affected with HD, one female at risk for HD, and one unaffected female spouse, ranging in age from 24 to 65 years. Six of the nine individuals with HD who committed suicide were single or divorced. Duration of HD symptoms ranged from 1 to 14 years. The single most important risk factor for suicide in HD was having no offspring. Other suicides in the family, being unmarried, having contact with others affected with HD, living alone, and depression slightly increased the risk of suicide. The suicide of an unaffected spouse and an individual at risk, but unaffected, emphasizes the heavy burden of HD on other family members. Recognition of the thesee risk factors should allow health care providers to assist families coping with HD and presymptomatic diagnosis. © 1993 Wiley‐Liss, Inc.
Natural history of trisomy 18 and trisomy 13: I. Growth, physical assessment, medical histories, survival, and recurrence risk
Authors: Baty Bonnie J. , Blackburn Brent L. , Carey John C.
Published: June 2005

The natural history of trisomy 18 and trisomy 13 was investigated using data derived from parent questionaires and medical records from 98 families with an index case of trisomy 18 and 32 families with an index case of trisomy 13. Data are presented on pregnancy, delivery, survival, medical complications, immunizations, growth, cause of death, cytogenetics, and recurrence risk. Half of the trisomy 18 babies were delivered by C‐section. Fetal distress was a factor in half, and the only reason in a third of C‐section deliveries. One minute Apgar scores were significantly lower in C‐section and breech deliveries. There were more small for gestational age babies than in the general population, but most of the low birth weight new borns were small for gestational age, unlike the general population. Survival in this group of children was better than in other studies due to ascertainment bias. There were more girls than boys at all ages for both conditions, and the sex ratio decreased with time. Growth curves for length, weight, head circumference, and weight vs height are provided. Long‐term survival did not appear to be due to mosaicism. We found no adverse reactions attributable to immunizations. At age 1 year there was an average of approximately 2 operations per living child. We report the second case of successful major cardiac surgery in a trisomy 18 child. Almost 70% of deaths were attributed to cardiopulmonary arrest. The sibling recurrence risk for trisomy 18 or trisomy 13 was 0.55%. © 1994 Wiley‐Liss, Inc.
Polydactyly, campomelia, ambiguous genitalia, cystic dysplastic kidneys, and cerebral malformation in a fetus of consanguineous parents: A new multiple malformation syndrome, or a severe form of oral–facial–digital syndrome type IV?
Authors: Adès L. C. , Clapton W. K. , Morphett A. , Morris L. L. , Haan E. A.
Published: June 2005

We describe a 27‐week fetus with occipitoschisis, polydactyly, campomelia, cleft palate, laryngeal dysplasia, ocular colobomata, hepatic fibrosis and intrahepatic cyst, ambiguous genitalia, cystic dyslstic kidneys, and brain malformation. This pattern of abnormalities appears unique. The differential diagnosis is discussed. The parents are first cousins, making autosomal recessive inheritance likely. © 1994 Wiley‐Liss, Inc.
Mutation analysis of 28 Gaucher disease patients: The Australasian experience
Authors: Lewis Barry D. , Nelson Paul V. , Robertson Evelyn F. , Morris C. Phillip
Published: June 2005

Gaucher disease is the most common lysosomal storage disease. It is an autosomal recessive disorder that results from a deficiency of β‐glucocerebrosidase. Three clinical phenotypes have been described: non‐neuronopathic, acute neuronopathic, and subacute neuronopathic. Genomic DNA from 28 Australasian patients of diverse ethnic origin with Gaucher disease was screened for 3 common mutations (1226G, 1448C and 84GG) using the amplification refractory mutation system (ARMS), and one uncommon mutation (1504T) by restriction enzyme digestion. Thirty‐eight of the 56 independent alleles in these patients were characterized, with 1448C present in 42% and 1226G in 28% of the alleles. The 1226G mutation was associated only with the non‐neuronopathic phenotype and 7 of the 15 patients who carried the 1448C mutation developed neuronopathic disease. Three infants who died in the neonatal period following a rapidly progressive neurodegenerative course carried no identifiable mutations. The 84GG mutation was carried by 2 Jewish patients and 1504T was present in one patient. It is now possible to rapidly identify the common Gaucher mutations using ARMS and restriction enzyme digestion, and our findings confirm the heterogeneity of mutations in Gaucher disease. It is also possible to predict in part the phenotypic outcome when screening patients for these mutations. We consider mutation analysis to be of most use in prenatal diagnosis and for carrier detection within affected families. © 1994 Wiley‐Liss, Inc.
Microphthalmia with linear skin defects (MLS) syndrome: Clinical, cytogenetic, and molecular characterization
Authors: Lindsay Elizabeth A. , Grillo Alessandra , Ferrero Giovanni B. , Roth Elizabeth J. , Magenis Ellen , Grompe Markus , Hultén Maj , Gould Clive , Baldini Antonio , Zoghbi Huda Y. , Ballabio Andrea
Published: June 2005

The microphthalmia with linear skin defects (MLS) syndrome (MIM 309801) is a severe developmental disorder observed in XX individuals with distal Xp segmental monosomy. The phenotype of this syndrome overlaps with that of both Aicardi (MIM 304050) and Goltz (MIM 305600) syndromes, two X‐linked dominant, male‐lethal disorders. Here we report the clinical, cytogenetic, and molecular characterization of 3 patients with this syndrome. Two of these patients are females with a terminal Xpter‐p22.2 delection. One of these 2 patients had an aborted fetus with anencephaly and the same chromosome abnormality. The third patient is an XX male with Xp/Yp exchange spanning the SRY gene which results in distal Xp monosomy. The extensive clinical variability observed in these patients and the results of the molecular analysis suggest that X‐inactivation plays an important role in determining the phenotype of the MLS syndrome. We propose that the MLS, Aicardi, and Goltz syndromes are due to the involvement of the same gene(s), and that different patterns of X‐inactivation are responsible for the phenotypic differences observed in these 3 disorders. However, we cannot rule out that each component of the MLS phenotype is caused by deletion of a different gene (a contiguous gene syndrome). © 1994 Wiley‐Liss, Inc.
Mild growth retardation and developmental delay, microcephaly, and a distinctive facial appearance
Authors: Partington Michael , Anderson Donald
Published: June 2005

We describe a brother and sister from one family and a girl from a second, unrelated family; they have a syndrome of pre‐ and postnatal growth deficiency, developmental delay, a friendly personality, microcephaly, and a distinctive facial appearance marked by thick eyebrows, full cheeks, and a short nose with the columella inserted below the nasal alae. We think this is a new syndrome probably inherited as an autosomal recessive trait. © 1994 Wiley‐Liss, Inc.
Another family with tricho‐rhino‐phalangeal syndrome type III (Sugio‐Kajii syndrome)
Authors: Nagai Toshiro , Nishimura Gen , Kasai Hideaki , Hasegawa Tomonobu , Kato Rumiko , Ohashi Hirofumi , Fukushima Yoshimitu
Published: June 2005

Tricho‐rhino‐phalangeal syndrome Type III (TRPS III) is a newly defined genetic entity. Only 9 patients in a family and one sporadic patient have been reported. We add another family in which 4 individuals in 3 generations are affected with this autosomal dominant trait. Although they manifested short stature, sparse hair, “pear‐shaped” nose, and coneshaped epiphyses, sharing these findings with TRPS Type I, the presence of a severe form of generalized shortness of all phalanges and metacarpals, and the absences of mental deficiency and exostoses in this family distinguish the disorder from the TRPS Types I and II. Their manifestations are quite similar to those of the patients reported as TRPS III (Sugio‐Kajii syndrome). © 1994 Wiley‐Liss, Inc.
Diffusion of information about neurofibromatosis type 1 DNA testing
Authors: Hofman Karen J.
Published: June 2005

There is little information available as to how individuals with genetic disorders receive information about the availability of DNA tests and what effect this has on their utilization. The purpose of this study was to survey centers where some individuals with neurofibromatosis type 1 (NF 1) are cared for, to establish how this type of information was disseminated. In 1990 announcement of the availability of testing for familial NF 1 was published in a newsletter of the National Neurofibromatosis Foundation (NNFF) and sent to individuals with NF 1 or NF 2 and their families, professionals, and NF centers in North America. Two years later these centers were surveyed to determine whether they had notified their patients of test availability. Of the 46 responding centers, 65% indicated they had attempted to notify their patients. The majority (80%) notified patients on an individual basis in clinic. The rest did so either on an individual basis in the clinic or by telephone or by letter or by a combination of these. Based on a survey response rate of 56% and approximately 1,000 enquiries received by the NNFF from families and physicians, it is concluded that 1) factors other than knowledge of test availability determined whether DNA testing for NF 1 was utilized; 2) some centers used testing more frequently than others; 100% of the referrals came from 40% of the centers, with 15% of referrals coming from a single center; 3) a significant percentage (35%) of NF centers did not inform their patients that DNA testing was available. © 1994 Wiley‐Liss, Inc.
Jarcho‐Levin syndrome: Unusual survival in a classical case
Authors: McCall Caroline P. , Hudgins Louanne , Cloutier Michelle , Greenstein Robert M. , Cassidy Suzanne B.
Published: June 2005

Spondylothoracic dysostosis, or Jarcho‐Levin syndrome, together with spondylocostal dysostosis, constitute a heterogeneous group of rare disorders characterized by short‐neck, short‐trunk dwarfism and multiple vertebral anomalies at all levels of the vertebral column. The latter include hemivertebrae, fused, hypoplastic, and “butterfly” vertebrae. In most cases of Jarcho‐Levin syndrome, the small size of the thorax causes respiratory death in infancy. This report of a Puerto Rican child with spondylothoracic dysostosis and unusually long survival to 11 years exemplifies the nosologic and prognostic difficulties associated with this syndrome. © 1994 Wiley‐Liss, Inc.
Elevated MSAFP levels and congenital heart defects: Lack of an association
Authors: Albar H. , MacDonald K. M. , Harman C. R. , Evans J. A. , Chodirker B. N.
Published: June 2005

This study was undertaken to evaluate the relationship between elevated maternal serum alpha fetoprotein (MSAFP) lavels and congenital heart defects. Thirty‐two infants with isolated major congenital heart defects and whose mothers had had MSAFP screening were identified. In only one case was the MSAFP greater than 2.3 multiples of the median. A review of our experience with women with elevated MSAFP levels did not document a higher rate of congenital heart malformations than would be expected based on estimated frequencies in the general population. © 1994 Wiley‐Liss, Inc.
Biparental inheritance of chromosome 21 polymorphic markers indicates that some Robertsonian translocations t(21; 21) occur postzygotically
Authors: Blouin Jean‐Louis , Binkert Franz , Antonarakis Stylianos E
Published: June 2005

Robertsonian translocations between acrocentric chromosomes are the most common structural chromosomal rearrangements in humans and many other organisms, and several mechanisms for their formation have been proposed. We have analyzed highly informative DNA polymorphisms in a family with a non‐mosaic de novo Robertsonian translocation 21q; 21q, to determine the parental origin of the two 21q arms of the rearranged chromosome. The genotypes indicated a biparental origin, i.e. one 21q was paternal and the other maternal. These results imply that in some cases the formation of the rob (21q; 21q) occurs in the zygote or in the first few postzygotic mitotic divisions. © 1994 Wiley‐Liss, Inc.
Two cases of Y; autosome translocations: A 45, X male and a clinically trisomy 18 patient
Authors: Farah Solange B. , Ramos Clarisa F. , de Mello Maricilda P. , Sartorato Edi L. , Horelli‐Kuitunen Nina , Lopes Vera L. G. S. , Cavalcanti Denise P. , Hackel Christine
Published: June 2005

We report on 2 cases of Y;autosome translocations. One is a male with normal external genitalia and 45,X karyotype without evidence of mosaicism or apparent translocation on cytogenetic analysis. In situ hybridization showed that the euchromatic portion of the Y‐chromosome is translocated to the chromosome 15. The other case is a clinically trisomy 18 male patient, with modal number of 46, a small metacentric marker with appearance of an i(18p) and cytogenetic and molecular evidence of Y;18 translocation. The occurrence of Y;18 translocation associated with clinical signs of trisomy 18 is reported here for the first time. © 1994 Wiley‐Liss, Inc.
Abnormality of type IX collagen in a patient with diastrophic dysplasia
Authors: Diab Mohammad , Wu Jiann‐Jiu , Shapiro Frederic , Eyre David
Published: June 2005

There is growing evidence that a spectrum of chondrodysplasias are caused by mutations in the gene coding for type II collagen. The basic molecular defect in diastrophic dysplasia has not been defined, but it appears not to be in collagen type II. Cartilage contains other tissue‐specific collagens, types IX, X, and XI, but no mutations have yet been found in their genes in clinical disease. Type IX collagen is hypothesized to play a role in the regulation of type II collagen fibril organization and structure in cartilage extracellular matrix. In this study, we have examined iliac crest growth cartilage from a patient with diastrophic dysplasia. Although collagen fibrils were markedly increased in diameter on transmission electron microscopy, type II collagen appeared to be normal biochemically. Type XI collagen was also normal. However, type IX collagen appeared abnormal on sodium dodecyl sulfate polyacrylamide gel electrophoresis with a pronounced excess of the COL1 domain of the molecule in pepsin extracts. The findings point to an abnormality in structure or metabolism of type IX collagen in diastrophic dysplasia. © 1994 Wiley‐Liss, Inc.
Duplication and deletion of chromosome band 2(p21p22) resulting from a familial interstitial insertion (2;11)(p21;p15)
Authors: Sawyer Jeffrey R. , Jones Emmett , Hawks Flora F. , Quirk J. Gerald , Cunniff Christopher
Published: June 2005

Routine amniocentesis for advanced maternal age led to the prenatal diagnosis of a fetus with a karyotype of a 46,XX,del(2)(p21p22). At delivery the baby had holoprosencephaly as the major clinical finding, which has been associated with a deletion of band 2p21 in several other case reports. Chromosome studies of the parents showed a normal 46,XY karyotype in the father, and a balanced interstitial insertion 46,XX dir ins (11;2)(p15.1;p21p22) in the mother. Subsequent chromosome studies of other relatives documented a 23‐year‐old half‐brother of the proposita with a partial trisomy for the segment deleted in the proposita. The half‐brother showed the derivative chromosome 11 from the mother, resulting in a 46,XY,der(11)dup(2)(p21p22) karyotype. Major clinical findings include short stature, mild development delay, and behavior abnormalities. A half‐sister of the proposita is also a balanced carrier of the dir ins (11;2) (p15.1;p21p22.2). The association of the deletion chromosome band 2p21 and the clinical finding of holoprosencephaly is further supported by the findings in this family. © 1994 Wiley‐Liss, Inc.
Achondrogenesis type IB (Fraccaro): Study of collagen in the tissue and in chondrocytes cultured in agarose
Authors: Freisinger P. , Stanescu V. , Jacob B. , Cohen‐Solal L. , Maroteaux P. , Bonaventure J.
Published: June 2005

A lethal chondrodysplasia characterized by extreme micromelia was diagnosed by ultrasound examination in two sibs whose nonconsanguineous parents were healthy. Radiographic and histopathologic data indicated that the two foetuses (18 and 21 weeks old) had achondrogenesis type IB (Fraccaro). Quantitation of total collagen extractable from dried cartilage samples demonstrated a 50% decrease when compared to an age‐related control. This decrease was essentially related to type II collagen. Nevertheless, the α chains and the CB peptides of type II collagen had a normal electrophoretic mobility. A significant amount of collagen type I was also detected. The electrophoretic pattern of collagens type IX and XI did not differ significantly from control sample.

The extracellular matrix elaborated by patient chondrocytes cultured in agarose for 10–12 days, contained less collagen type II than normal cells. Labelling with 14C‐proline of cultured cells showed the presence of pro‐collagen and type II collagen chains with a normal electrophoretic mobility, but an α2(I) chain was detectable in the patient material, indicating the presence of collagen type I which supported the tissue findings. The significance of the type II collagen reduction in the patient's cartilage is unclear but it is unlikely to be the primary defect in achondrogenesis type I. © 1994 Wiley‐Liss, Inc.