bluuebunny/crossref_metadata_2025 huggingface dataset:
Non‐collagenous protein screening in the human chondrodysplasias: Link proteins, cartilage oligomeric matrix protein (COMP), and fibromodulin
Authors: Stanescu Victor , Do Thuc Pham , Chaminade Françoise , Maroteaux Pierre , Stanescu Ritta
Published: June 2005

A gel‐electrophoretic screening for link proteins, cartilage oligomeric matrix protein (COMP), and fibromodulin abnormalities was performed in fetuses, newborn infants, and children with various types of chondrodysplasia. Microdissected freeze‐dried sections of upper tibial growth cartilage were extracted with 4M guanidinium chloride in the presence of proteolysis inhibitors. After dialysis against 8M urea, the extracts were submitted to stepwise ion‐exchange chromatography to separate the large proteoglycans (aggrecans) from the other components. The latter were analyzed by gel electrophoresis, electrotransferred onto nitrocellulose membranes, and reacted with specific antibodies. Control samples from individuals with apparently normal growth were analyzed in the same runs.

Two link protein bands with abnormal electrophoretic migration were found in a sporadic case of spondylometaphyseal dysplasia, Kozlowski type. Three link protein bands with the same migration as in the control samples were found in thanatophoric dysplasia, homozygous achondroplasia, achondrogenesis type II, hypochondrogenesis, Goldblatt syndrome, Desbuquois dysplasia, pseudo‐achondroplasia, and diastrophic dysplasia. In several pathologic cases with normal electrophoretic pattern of the link proteins, small link protein fragments appeared after reduction.

The gel electrophoretic pattern of COMP was studied in thanatophoric dysplasia, diastrophic dysplasia, homozygous achondroplasia, fibrochondrogenesis, hypochondrogenesis, Goldblatt syndrome, and Kniest dysplasia. In all these cases the pattern was the same as in the control samples.

The main band of fibromodulin had a normal migration rate in fibrochondrogenesis, Desbuquois dysplasia, Kniest dysplasia, and pseudoachondroplasia. It was delayed in diastrophic dysplasia. © 1994 Wiley‐Liss, Inc.
Autosomal recessive proximal spinal muscular atrophy in 101 sibs out of 48 families: Clinical picture, influence of gender, and genetic implications
Authors: Rudnik‐Schöneborn Sabine , Röhrig Dorothee , Morgan Graeme , Wirth Brunhilde , Zerres Klaus
Published: June 2005

We analysed the clinical picture of 101 sibs (43 sib pairs, 5 triplets) with autosomal recessive proximal spinal muscular atrophy (SMA). Linkage data of 20 sibships, which were available for analysis, were in agreement with chromosome 5q linkage. The patients were classified according to the motor development into SMA I (never sat), SMA II (sitting without support), and SMA III (walking without aids). Three sibs with adult onset (>30 years = SMA IV) were discussed as a separate entity. Age‐of‐onset of the 101 patients showed a wide spectrum (prenatal to 47 years). Among sib pairs with SMA I and SMA II the ages‐of‐onset appeared to be very similar except of one atypically discordant sib pair. With regard to SMA III, 3 out of 13 sibships (23%) showed a marked variation in age‐of‐onset ranging from 5–15 years within a family.

Concerning acquired motor development (ability to sit and walk), 7 sibships (15%) belonged to different SMA types. Ages of death in 29 sib pairs in whom at least one sib had died before the age of 20 years were strikingly discordant. Neither the degree of disability nor the respiratory deficits are reliable predictors of life expectancy. Although a predominance of males can be observed, no significant effect of gender has been established in familial cases. The existence of multiple allelism seems to be the most suitable explanation for the high interfamilial variability considering the clinical concordance in most affected sib pairs. © 1994 Wiley‐Liss, Inc.
Spontaneous abortion–high risk factor for neural tube defects in subsequent pregnancy
Authors: Carmi R. , Gohar J. , Meizner I. , Katz M.
Published: June 2005

An increased spontaneous abortion rate has been observed in pregnancies preceding that of fetuses or newborn infants with neural tube defects (NTDs). There are 2 suggested explanations for this observation. One is that a trophoblastic cell rest, remaining from a previous aborted pregnancy, interferes with normal embryogenesis. The second is that the previous lost fetus was affected with NTD. We studied the obstetric history of mothers of newborn infants with NTDs compared to those with other birth defects, in low and high risk groups for NTD (Jew and Bedouins). A significantly higher spontaneous abortion rate (48%) in the preceding pregnancy was found in the NTD group compared to the group with other birth defects (20%). This was especially remarkable for spina bifida cases in the Jewish study population. A significantly higher rate of preceding spontaneous abortion was also found in congenital heart defects (CHD) when compared to other congenital malformations. A hypothesis based on the multifactorial threshold model is put forward to explain these findings. Based on the realization that spontaneous abortion constitutes a high risk factor for NTD and possibly also CHD, we recommend a delay of subsequent pregnancy and periconceptional treatment with folic acid following spontaneous abortion. © 1994 Wiley‐Liss, Inc.
Seckel syndrome in a Yemeni family in Saudi Arabia
Authors: Krishna A. G. , Scrimgeour E. M. , Zawawi T. H.
Published: June 2005

We studied a 28‐year‐old Yemeni woman with typical Seckel syndrome. Two deceased sibs, a twin sister and a brother, had also been affected. The father of these individuals was married to his cousin's daughter: the pedigree suggests autosomal recessive inheritance. Classical Seckel syndrome has not been reported previously in Arabs, and this appears to be the first report from the Middle East. © 1994 Wiley‐Liss, Inc.
Oral‐facial‐digital syndrome with retinal abnormalities: OFDS type IX. A further case report
Authors: Nevin N. C. , Silvestri J. , Kernohan D. C. , Hutchinson W. M.
Published: June 2005

The oral‐facial‐digital syndromes (OFDS) are a heterogeneous group. Recently, Gurrieri et al. [1992: Am J Med Genet 42:789–792] described a new OFDS characterised by typical oral, facial and digital abnormalities but distinguishable from previously reported OFDS by the presence of retinochoroidal lacunae of an apparently colobomatous origin. Toriello [1993: Clin Dysmorph 2:95–105] designated this possible new OFDS as Type IX. We describe a young woman presenting with oral, facial and digital anomalies and with the specific retinal abnormality reported by Gurrieri et al. [1992], thus confirming the existence of OFDS Type IX. As the patients of Gurrieri et al. [1992] were two affected brothers, they were unable to distinguish between autosomal and X‐linked recessive inheritance. As our patient is an affected female, an autosomal recessive mode of inheritance is more likely. © 1994 Wiley‐Liss, Inc.
Does IQ decline with age in fragile‐X? A methodological critique
Authors: Hay David A.
Published: June 2005

The recent claims for a decline in intelligence test performance in males and females with fragile‐X (fra(X)) syndrome have implications both clinically and in evaluating the underlying neurological basis. This commentary identifies three key issues in evaluating evidence for a decline and in planning future, more co‐ordinated efforts. These are (1) problems in combining data across different intelligence tests and/or different ages with potentially incompatible norms, task demands, and models of the structure of intelligence; (2) limitations in applying to low ability persons tests designed to discriminate best around the population average; and (3) specific cognitive deficits and behavioral problems in fra(X) individuals which may be confounded with the task demands of particular IQ tests at particular ages. While the decline in ability may be a real phenomenon rather than an artifact, recommendations are made about the psychometric requirements for a larger and more definitive collaborative study. © 1994 Wiley‐Liss, Inc.
Transmitting males and carrier females in fragile X–revisited
Authors: Loesch Danuta Z. , Hay David A. , Mulley John
Published: June 2005

Fragile X “transmitting males” have customarily been defined as phenotypically normal hemizygotes, who show very few or no fragile sites, and who transmit the fragile X premutation to phenotypically normal daughters. However, an objective justification of this definition was lacking. The discovery of an unstable CCG repeat as the genetic basis of fragile X further emphasized the apparent distinction between the “normal transmitting males” with short repeat and expression of the FMR1 gene, and the affected males with larger repeats (Δ > 0.6 kb) and a complete lack of FMR1 transcription. We have recently shown that the transition between these two groups in phenotypic expression of fragile X is gradual, mainly on account of methylation mosaicism. However, there were insufficient data on the phenotype within the short repeat (0.0 < Δ < 0.6) range. In this paper we approach this problem by comparing some clinical, anthropometric, and psychometric data from a sample of normal transmitting males with those from their non‐fragile X male relatives. Moreover, female carriers with short repeat are compared for the same traits with their non‐fragile X female relatives. The results have shown that both males and females with a short repeat differed significantly from normal on several psychometric and physical measurements, and males only showed differences in typical facial traits. Further studies of genotype‐phenotype correlations within the short repeat range, including the estimate of FMR1 gene function and a more exact estimate of repeat size, is required before genetic explanation for the clinical findings can be provided. It is recommended that, in the meantime, the clinical definition of transmitting males or female carriers as “normal” should be replaced by “low expressing.” © 1994 Wiley‐Liss, Inc.
Mental retardation, congenital heart defect, cleft palate, short stature, and facial anomalies: A new X‐linked multiple congenital anomalies/mental retardation syndrome: Clinical description and molecular studies
Authors: Hamel Ben C. J. , Mariman Edwin C. M. , van Beersum Sylvia E. C. , Schoonbrood‐Lenssen Anneke M. J. , Ropers Hans‐Hilger
Published: June 2005

We report on two brothers and their two maternal uncles with severe mental retardation, congenital heart defect, cleft or highly arched palate, short stature and craniofacial anomalies consisting of microcephaly, abnormal ears, bulbous nose, broad nasal bridge, malar hypoplasia, and micrognathia. Three of the four patients died at an early age. The mother of the two brothers had an atrial septal defect. She is assumed to be a manifesting carrier of a mutant gene, which is expressed in her two sons and two brothers. By multipoint linkage analysis it is found that the most likely location of the responsible gene is the pericentromeric region Xp21.3‐q21.3 with DMD and DXS3 as flanking markers. Maximum information is obtained with marker DXS453 (Z = 1.20 at θ =0.0). © 1994 Wiley‐Liss, Inc.
Cardiac abnormalities in the Bardet‐Biedl syndrome: Echocardiographic studies of 22 patients
Authors: Elbedour Khalil , Zucker Nili , Zalzstein Eli , Barki Yechiel , Carmi Rivka
Published: June 2005

The Bardet‐Biedl syndrome is an autosomal recessive disorder of polydactyly, obesity, tapetoretinal degeneration, mental retardation, hypogenitalism, and renal involvement. A high incidence of congenital and acquired heart disease was reported in the former “Laurence‐Moon‐Biedl‐Bardet” syndrome. However, since the establishment of the Bardet‐Biedl syndrome as a separate clinical entity, cardiac involvement has not been evaluated in this disorder. We have performed echocardiographic studies on 22 patients with the Bardet‐Biedl syndrome from three extended, highly inbred Bedouin families. In addition to previously reported congenital heart defects we have observed hypertrophy of the interventricular septum and dilated cardiomyopathy. Our findings of cardiac involvement in 50% of the cases suggest that echocardiographic examination should be included in the clinical evaluation and follow‐up of patients with Bardet‐Biedl syndrome. © 1994 Wiley‐Liss, Inc.
Megalocornea‐mental retardation syndrome: An additional case
Authors: Antiñolo Guillermo , Rufo Miguel , Borrego Salud , Morales Celia
Published: June 2005

In 1975, Neuhaüser (Z Kinderheilk 120:1–8) reported on a recessively inherited entity comprising mental retardation, megalocornea, and seizures. The megalocorneamental retardation (MMR) syndrome (MIM 249310) is a rare entity. There have been 19 previously published cases and the clinical differences observed between reported patients have raised questions regarding the nosology of the syndrome and the issue of heterogeneity versus variability. We report on a new case: a 26/12‐year‐old boy, first child of nonconsanguineous healthy parents with megalocornea (corneal diameter ⩽ 13 mm), delayed psychomotor development and hypotonia, plus minor facial anomalies. © 1994 Wiley‐Liss, Inc.
Linkage analyses of chromosome 6 loci, including HLA, in familial aggregations of Crohn disease
Authors: Hugot Jean Pierre , Laurent‐Puig Pierre , Gower‐Rousseau Corine , Caillat‐Zucman Sophie , Beaugerie Laurent , Dupas Jean‐Louis , Van Gossum André , Bonaïti‐Pellie Catherine , Cortot Antoine , Thomas Gilles , G.E.T.A.I.D.
Published: June 2005

Segregation analyses of familial aggregations of Crohn disease have provided consistent results pointing to the involvement of a predisposing gene with a recessive mode of inheritance. Although extensively investigated, the role played by human leucocyte antigen (HLA) genes in this inflammatory bowel disease remains elusive and the major histocompatibility complex is a candidate region for the mapping of the Crohn disease susceptibility gene. A total of 25 families with multiple cases of Crohn disease was genotyped for HLA DRB1 and for 16 highly polymorphic loci evenly distributed on chromosome 6. The data were subjected to linkage analysis using the lod score method. Neither individual nor combined lod scores for any family and for any locus tested reached values suggesting linkage or genetic heterogeneity. The Crohn disease predisposing locus was excluded from the whole chromosome 6 with lod scores less than −2. It was excluded from the major histocompatibility complex and from 91% of the chromosome 6 genetic map with lod scores less than −4. The major recessive gene involved in genetic predisposition to Crohn disease does not reside on the major histocompatibility complex nor on any locus mapping to chromosome 6. © 1994 Wiley‐Liss, Inc.
Segregation analysis of smoking‐associated malignancies: Evidence for mendelian inheritance
Authors: Sellers Thomas A. , Chen Ping‐Ling , Potter John D. , Bailey‐Wilson Joan E. , Rothschild Henry , Elston Robert C.
Published: June 2005

Tobacco consumption is an established risk factor for cancer at a number of sites: oral cavity, esophagus, nasopharynx, lung, larynx, pancreas, bladder, kidney, and uterine cervix. These sites also demonstrate familial aggregation. To determine if evidence exists for a major gene controlling susceptibility to smoking‐associated cancers, maximum likelihood segregation analyses were performed on 337 families (3,276 individuals) ascertained through a deceased lung cancer proband. Models were fitted that allowed for personal tobacco use and variable age of onset. The hypotheses of environmental transmission and no major gene were rejected (P < 0.005), but none of the Mendelian models could be distinguished. According to Akaike's Information Criterion, Mendelian dominant inheritance of an allele that produces cancer at an earlier age of onset provided the best fit to the data. The model suggests that 62% of the population are susceptible, and that the mean age‐of‐onset differs for men and women: at the mean level of tobacco exposure, female gene carriers are affected, on average, 24 years earlier than non‐carriers (77 vs. 101), while in males the difference was 20 years (71 vs. 91). These findings extend our earlier observations on the genetic epidemiology of lung cancer and suggest that Mendelian factors may influence the risk of cancers that are known to be smoking associated. © 1994 Wiley‐Liss, Inc.
10p Duplication characterized by fluorescence in situ hybridization
Authors: Wiktor Anne , Feldman Gerald L. , Kratkoczki Pamela , Ditmars Donald M. , Van Dyke Daniel L.
Published: June 2005

We describe a patient with severe failure to thrive, mild‐moderate developmental delay, cleft lip and palate, and other anomalies. Routine cytogenetic analysis documented a de novo chromosome rearrangement involving chromosome 4, but the origin of the derived material was unknown. Using chromosome specific painting probes, the karyotype was defined as 46,XY, der(4) t(4;10)(q35;p11.23). Characterization of the dup(10p) by fluorescence in situ hybridization (FISH) analysis provides another example of the usefulness of this technology in identifying small deletions, duplications, or supernumerary marker chromosomes. © 1994 Wiley‐Liss, Inc.
Apparently normal frequency of congenital anomalies in the highly polluted town of Cubatão, Brazil
Authors: Monteleone‐Neto Roque , Castilla Eduardo E.
Published: June 2005

Anencephaly is Suspected to cluster in the municipality of Cubatão (Brazil), and is attributed to industrial pollution. We surveyed malformations prospectively in 10,000 births, in 3 consecutive series, corresponding to 3 maternity hospital in Cubatão, under working definitions and norms taken from the ECLAMC (Latin American Collaborative Study of Congenital Malformations). The sample from Cubatão had a higher proportion of black racial ancestry, and lower frequencies for stillbirths and for immediate neonatal death, than in the rest of South America.

The birth prevalence of malformations varied between the 3 hospitals in Cubatão, due to differences in ascertainment of minor defects. A higher‐than‐expected prevalence rate in Cubatão was observed only for postaxial polydactyly, probably due to a higher proportion of black racial ancestry, while lower‐than‐expected rates were obtained for congenital dislocation of the hip, and for babies with multiple congenital anomalies patterns, both of them attributed to underascertainment of minor defects.

These observations do not support the suspicion of an elevated birth prevalence rate for anencephaly, neural tube defects, or any other major congenital malformation in Cubatão. © 1994 Wiley‐Liss, Inc.
Male‐to‐male transmission of mild Bachmann‐de Lange syndrome
Authors: Chodirker Bernard N. , Chudley Albert E.
Published: June 2005

We report on a father and son with mild Brachmann‐de Lange syndrome. Previous reports have documented apparent autosomal dominant transmission; however, only one example of male‐to‐male transmission of possible Brachmann‐de Lange syndrome has been reported. This case provides further evidence of the existence of an autosomal dominant form of Brachmann‐de Lange syndrome. © 1994 Wiley‐Liss, Inc.
Aarskog‐Scott syndrome: Confirmation of linkage to the pericentromeric region of the X chromosome
Authors: Stevenson Roger E. , May Melanie , Arena J. Fernando , Millar Edward A. , Scott Charles I. , Schroer Richard J. , Simensen Richard J. , Lubs Herbert A. , Schwartz Charles E.
Published: June 2005

Aarskog‐Scott syndrome was tentatively mapped to Xq13 on the basis of an X:8 translocation by Bawle et al. [Am J Med Genet 17:595–602, 1984]. A review of the cytogenetics and the use of molecular markers in that family have resulted in revision of the breakpoints of the translocation to Xp 11.2 and 8q11.21 [Glover et al., Hum Mol Genet 2:1717–1718, 1993]. Two famillies including one of the two initial families with Aarskog‐Scott syndrome [Scott, BD:OAS VII (6): 240–246, 1971], have participated in our study to evaluate the localization of the gene for Aarskog‐Scott syndrome to the pericentromeric region of the X chromosome. Using a series of DNA probes, we have been able to confirm linkage to the X chromosome, with multipoint analysis indicating the most likely localization of the gene to be on the proximal short arm. © 1994 Wiley‐Liss, Inc.
Familial Angelman syndrome, with a crossover in the critical deletion region
Authors: Nelen M. R. , Van der Burgt C. J. A. M. , Nillesen W. N. , Vis A. , Smeets H. J. M.
Published: June 2005

More than two thirds of the patients with Angelman syndrome (AS) carry a deletion or other chromosomal abnormality in the 15q11–13 region. A much less frequent cause (4%) is paternal uniparental disomy of the entire chromosome. In general no abnormalities are detectable in familial cases and an inherited submicroscopic deletion was described only once. Here a familial case of 2 sibs with AS is reported. No major cytogenetic or molecular abnormality was identified, but a recombination event had occurred in the AS critical region. The AS locus, D15S113, D15S10, D15S11, and D15S18 mapped proximal and the GABRB3 gene, D15S97, the GABRA5 gene, and D15S12 distal to the crossover site. This recombination within the AS critical region confirmed the exclusion of GABRB3 as a candidate gene for AS. Other markers and candidate genes can be tested genetically as well for a possible role in AS. © 1994 Wiley‐Liss, Inc.
Poland anomaly with unusual associated anomalies: Case report of an apparent disorganization defect
Authors: Kabra Madhulika , Suri Mohnish , Jain Usha , Verma Ishwar C.
Published: June 2005

We report on a 2 1/2‐year‐old boy with absence of clavicular head of pectoralis major on the left side, ipsilateral upper limb anomalies, ans anomalies of the lower limbs such as popliteal webbing, median cleft of right foot, bifid left hallux, syndactyly of toes, and toenail hypoplasia. Other anomalies included undescended testis, hairy nevus in the lumbosacral region, and a pedunculated fingerlike tag on the right thigh. The pathogenesis of these associated anomalies cannot be explained on the basis of compromised local blood supply alone. A possible link with the disorganization mutation is discussed. © 1994 Wiley‐Liss, Inc.
Joubert syndrome with congenital hepatic fibrosis: An entity in the spectrum of oculo‐encephalo‐hepato‐renal disorders
Authors: Lewis S. M. E. , Roberts E. A. , Marcon M. A. , Harvey E. , Phillips M. J. , Chuang S. A. , Buncie J. R. , Clarke J. T. R.
Published: June 2005

Joubert syndrome is an autosomal recessive inherited condition characterized by agenesis or hypoplasia of the cerebellar vermis, retinal dystrophy, chorioretinal colobomata, oculomotor abnormalities, episodic hyperpnea, ataxia, and mental retardation. Congenital hepatic fibrosis has not previously been described in Joubert syndrome. We report two unrelated children with Joubert syndrome and hepatosplenomegaly. On histopathological examination, both had congenital hepatic fibrosis. Both were also found to have congenital medullary cystic disease of the kidneys. Joubert syndrome appears to be one of a spectrum of congenital malformation syndromes involving the central nervous system, eye, liver and kidneys. © 1994 Wiley‐Liss, Inc.
Artistic and documentary evidence for tetradysmelia from sixteenth century England
Authors: Anderson Trevor
Published: June 2005

A series of illustrative ballads provide evidence of tetradysmelia, including acheiropodia, from sixteenth century England. It is probable that the presented malformations represent the non‐genetic Hanhart complex. Such a condition has not been reported in archaeologically retrieved skeletal material. © 1994 Wiley‐Liss, Inc.
Identification of marker chromosomes in thirteen patients using FISH probing
Authors: Daniel Art , Malafiej Paul , Preece Kerrie , Chia Nicole , Nelson John , Smith Meryl
Published: June 2005

Fourteen marker chromosomes were studied by FISH (fluorescence in‐situ hybridization) in cytogenetic preparations from 13 patients. The derived markers were identified as one isodicentric bisatellited mar(22), one fragment sized r(X), one fragment sized r(Y), one i(18p), small autosomal ring markers in three different patients derived from chromosomes 2, 8, and 8, a marker comprised of 9p and part of 9qh, and 3 bisatel‐ lited apparently monocentric markers; one of each from chromosomes 13 or 21, 14 or 22, and 15. Two fragment sized small ring markers in one patient and a small ring marker in another were negative with all twenty‐two different probes used. In addition, the small ring marker Y chromosome that was found in a boy with karyotype 46, X,−Y,+mar was negative with both pDXZ1 and pDYZ3. This anomaly of negative results with the battery of centromeric alphoid probes can be explained if one breakpoint for some small ring markers is very near to or within the centromere. Only some of the pericentromeric repetitive sequences in the normal chromosome would be represented in the chromosome specific alphoid probes, and presumably those corresponding to the currently available probes are truncated during the formation of the unidentified markers. In three of the small ring markers the FISH signal on the marker was much stronger than on the normal homologues in various proportions of cells, and this may indicate that some of the fragment sized small rings were multicentric. The literature was reviewed for Distamycin A/DAPI negative small ring markers that were present as extra chromosomes. There were only single published cases of most small rings but there were three r(8) cases, two r(l) cases, two r(12) cases, and two r(20) cases, uncomplicated by the presence of other chromosome abnormalities. Most cases with similar small rings were quite dissimilar phenotypically and syndrome identification was not possible, but in pooled data, 18/23 (about 80%) were developmentally and/or phenotypically abnormal. Some patients (5/23, about 20%) with small rings were dysmorphic without intellectual handicap. Of 28 such patients with small ring markers (Distamycin/Dapi negative) in pooled data there are 6 (about 20%) with multiple markers mostly derived from different chromosomes. This is a very high figure and would suggest that the ring formation events, although involving different chromosomes, must be related and must be an indicator of the mechanism of origin of this group of markers. © 1994 Wiley‐Liss, Inc.
Microscopic neuroblastoma in a fetus with a de novo unbalanced translocation 3;10
Authors: Qureshi Faisal , Jacques Suzanne M. , Johnson Mark P. , Reichler Avihai , Evans Mark I.
Published: June 2005

We report on a fetus with a de novo unbalanced translocation 3;10 and a microscopic neuroblastoma. The fetus had the kary‐otypic and phenotypic manifestations of partial dup (3q). The finding of a constitutional chromosomal abnormality and a microscopic neuroblastoma, although possibly coincidental, supports Knudson's two hit hypothesis for development of neuroblastomas and other embryonal tumors. In this case the first mutation is represented by the constitutional abnormality, possibly resulting in the microscopic neuroblastoma. A second mutation affecting the abnormal cells, which may be more prone to mutagenesis, may trigger a neuroblastoma. © 1994 Wiley‐Liss, Inc.
Earliest description by Johann Friedrich Meckel, Senior (1750) of What is known today as Lutembacher syndrome (1916)
Authors: Wiedemann Hans‐Rudolf
Published: June 2005

The letter that the famous anatomist Johann Friedrich Meckel, Sr. sent from Berlin on May 5, 1750 to the great Albrecht von Haller (at that time resident in Göttingen) contains the earliest reference to an unusual observation made by the former. Even today this observation is considered in the clinical literature to be the first description of a coarctation of the aorta. In fact, it is probably the first description of what is known today as Lutembacher syndrome. © 1994 Wiley‐Liss, Inc.
Microcephaly, lymphedema, and chorioretinal dysplasia: Report of two additional cases
Authors: Angle Brad , Holgado Sandra , Burton Barbara K. , Miller Marilyn T. , Shapiro Michael J. , Opitz John M.
Published: June 2005

In recent years, several patients with microcephaly, lymphedema and chorioretinal dysplasia have been described. We have studied two additional patients with similar findings. The question of whether microcephaly with lymphedema and microcephaly with chorioretinal dysplasia and lymphedema are distinct entities remains unanswered. Identification of other patients in the future may provide additional information. © 1994 Wiley‐Liss, Inc.
Epidemiological and genetic studies of congenital profound deafness in the general population of Sichuan, China
Authors: Liu Xuezhong , Xu Lirong , Zhang Silin , Xu Yin
Published: June 2005

People with congenital profound deafness (CPD) were surveyed in the general population of Sichuan. The prevalence was 0.082% (104/126, 876) of the general population, male 0.086%, female 0.078%. There was no significant difference in prevalence between urban and rural populations. However, the population living in the mountains had a much higher prevalence than people from the foothills and plains (P < 0.05). Amongst the nationalities investigated, there were significant differences in prevalence. Non‐Chinese, except for Tibetans, presented a significantly higher prevalence than Han Chinese. There was a significantly higher prevalence among the inbred population (0.82%) than among the non‐inbred population (0.072%). An effect of parental age was demonstrated, but no effect of birth order was found. There was a significant seasonal variation in prevalence. Inherited cases could account for 71.2% of all cases, of which 92% were autosomal recessive (AR) and 8% autosomal dominant (AD). Heterogeneity in AR was found with at least 8 different loci. The fitness was 60.26%, the coefficient of selection was 0.3974, mutation rate was estimated to be 2.0 × 10 −4, and no heterozygote advantage was proven. © 1994 Wiley‐Liss, Inc.
Oral‐facial‐digital syndrome: Report on a transitional type between the Mohr and Váradi syndromes in a fetus
Authors: Camera Gianni , Marasini Maurizio , Pozzolo Silvano , Camera Andrea
Published: June 2005

Oral‐facial‐digital syndromes (OFDS) constitute a heterogeneous group of entities whose clinical manifestations are often overlapping. We report on a 23‐week‐old aborted fetus who showed a transitional phenotype between OFD II and OFD VI syndromes. © 1994 Wiley‐Liss, Inc.
Pitfalls of genetic counselling in brachydactyly type C
Authors: Camera Gianni , Camera Andrea , Costa Margherita , Mantero Renzo
Published: June 2005

A familial case of brachydactyly type C is presented in which hand radiographs of the proposita's parents was considered normal. The metacarpophalangeal profile pattern of the mother's hands demonstrated minimal manifestations typical of brachydactyly type C. © 1994 Wiley‐Liss, Inc.
Dermatoglyphic peculiarities in patients with Williams‐Beuren syndrome
Authors: Rodewald Alexander , Pankau Rainer , Gosch Angela , Wessel Armin
Published: June 2005

The dermatoglyphic patterns of fingertips and palms of 115 patients with Williams‐Beuren syndrome (WBS) were analysed and compared with the data from 199 control individuals from Germany. The following combination of dermatoglyphic patterns appears to be characteristic to WBS: an excess of whorls on all fingertips; high termination values of the main lines D, B, and A; frequent absence of C triradius (C°); high frequencies of ulnar loops on the hypothenar and distal loops on the 2nd, 3rd, and 4th inter digital areas, of distal axial triradii t", and of abnormal palmar creases such as simian crease and Sydney lines. The combination of fingertip and palmar patterns expressed by a “Log.Score‐Index,” provides a high degree of discrimination between the WBS patients (92%) and the control group (88%). A “phantom picture” for WBS was constructed, which can be used for its diagnosis. © 1994 Wiley‐Liss, Inc.
Tetrasomy 21 pter→q22.1 and Down syndrome: Molecular definition of the region
Authors: Daumer‐Haas Cornelia , Schuffenhauer Simone , Walther Joachim U. , Schipper Roberton D. , Porstmann Tomas , Korenberg Julie R.
Published: June 2005

Down syndrome is usually caused by complete trisomy 21. Rarely, it is due to partial trisomy of the segment 21q22. We report on a 33‐month‐old girl with tetrasomy 21 pter → q22.1 resulting from an extra chromosome idic(21)(q22.1). She has craniofacial traits typical of Down syndrome, including brachycephaly, third fontanel, upward slanting palpebral fissures, round face, and protruding tongue. Speech development is quite delayed whereas motor development is only mildly retarded. The molecular content of the extra isodicentric chromosome was defined by molecular genetic investigations using 13 single copy probes unique to chromosome 21, and SOD1 expression studies. The child was found to have 4 copies of the region defined by D21S16 (21cen) through D21S93 on 21q22.1 and two copies of the remaining region defined by SOD1 → D21S55 → D21S123. In view of the recent assignment of Down syndrome facial characters to the 21q22 region, defined in part by D21S55, it is significant that this child shows a subset of Down syndrome facial manifestations, without duplication of this region. These results suggest that genes contributing to the facial and some of the hand manifestations of Down syndrome also exist in the chromosomal region proximal to D21S55 in band 21q22.1. © 1994 Wiley‐Liss, Inc.
Schinzel‐Giedion syndrome: Autopsy report and additional clinical manifestations
Authors: Rodríguez José Ignacio , Jiménez‐Heffernan José A. , Leal Julia
Published: June 2005

Schinzel‐Giedion syndrome (SGS) is a rare and incompletely defined condition. This is the third postmortem study on a boy with SGS and other unusual findings. He had a primitive neuroectodermal tumor in the lumbosacral region, bilateral syndactyly of hands and feet, and brain anomalies in addition to the major manifestations of the syndrome. We consider these clinical findings as possible additional manifestations of the syndrome since, of 19 SGS patients reported, 4 had syndactyly and 3 had embryonal tumors. In addition, the 3 published necropsy studies report brain anomalies. Knowledge that these changes occur in SGS may help facilitate diagnosis and improve our understanding of the syndrome. © 1994 Wiley‐Liss, Inc.
Psychological costs and benefits of predictive testing for Huntington's disease
Authors: Codori Ann‐Marie , Brandt Jason
Published: June 2005

The impact of predictive genetic testing for Huntington's disease (HD) was assessed in 68 persons at high (n = 17) or low risk (n = 51) for the disease at one to six years following disclosure of test results. There was consensus in both groups that knowledge of HD genetic status was beneficial. A majority of persons felt relief from wondering and uncertainty. High‐risk persons identified greater family closeness and financial security. For low‐risk persons, the knowledge that their children were spared offered great consolation. Negative effects in high‐risk persons were psychological burden (worry, guilt). Even for low‐risk subjects, there was a period of adjustment and, in some, disappointment that low risk had not alleviated problems unrelated to HD. Although the majority of marriages were unaffected by testing, some persons in both groups reported that their marriages sustained positive or negative impact. Despite mixed consequences, most did not regret being tested. The benefits of testing appear to outweigh its drawbacks, at least among this self‐selected group of research participants. We also must conclude, however, that predictive genetic testing will result in negative as well as positive consequences, regardless of test outcome. © 1994 Wiley‐Liss, Inc.
Association of the apolipoprotein E ϵ4 allele with clinical subtypes of autopsy‐confirmed Alzheimer's disease
Authors: Zubenko George S. , Stiffler Scott , Stabler Stacy , Kopp Ursula , Hughes Hugh B. , Cohen Bruce M. , Moossy John
Published: June 2005

Consistent with previous reports, we observed a significant association of the APOE ϵ4 allele with Alzheimer's Disease (AD) in a series of 91 autopsy‐confirmed cases. The ϵ4 allele frequency was higher in cases with a family history of AD‐like dementia (0.54 ± 0.07), although the ϵ4 allele frequency in the AD cases with a negative family history (0.38 ± 0.05) remained significantly greater than that for the non‐AD control group (0.13 ± 0.03). A similar increase in ϵ4 allele frequency (0.54 ± 0.07) was observed in the AD cases with amyloid angiopathy, compared to those who did not have amyloid angiopathy (0.36 ± 0.04). Contrary to previous reports, no effect of the dosage of the ϵ4 allele was found on the age of onset of dementia among the AD cases and, contrary to reports suggesting an association of ϵ4 and atherosclerosis, the ϵ4 allele frequency was similar in cases with or without concurrent brain infarcts. Modest but consistent correlations were observed between the dosage Of ϵ4 alleles and the cortical density of senile plaques, but not neurofibrillary tangles. The last finding suggests that the pathogenic events mediated by the ϵ4 allele may be more directly involved in the formation of senile plaques, the identifying lesions in AD, than neurofibrillary tangles. A robust association of both the presence of an ϵ4 allele and a family history of AD‐like dementia with concurrent amyloid angiopathy occurred within our sample of AD cases. This association arose from an interaction of the ϵ4 allele with a separate familial factor for which a family history of dementia served as a surrogate. These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE ϵ4 allele. © 1994 Wiley‐Liss, Inc.
Knowledge of genetics and attitudes toward genetic testing in two hereditary ataxia (SCA 1) Kindreds
Authors: Nance Martha A. , Sevenich Ellen A. , Schut Lawrence J.
Published: June 2005

Molecular genetic predictive or prenatal genetic testing is now possible in families with one form of adult‐onset, autosomal dominant ataxia (SCA 1). Before the SCA 1 gene was isolated, we began a study of the knowledge of genetics, the perception of the disease, and the intended use of genetic testing among members of two large SCA 1 kindreds.

Questionnaires were sent to 210 consenting affected, at‐risk, and spouse members of two SCA 1 kindreds; data from the 117 respondents were analyzed on a personal computer.

Sixty‐nine percent of respondents thought predictive testing (by genetic linkage) should be made available immediately, and 42% thought prenatal testing should be made available. The kindreds differed in several important aspects: knowledge of genetic concepts, family size, and anticipated emotional responses to genetic testing. No respondent had obtained individualized genetic counseling.

There is moderate interest in genetic testing for this fatal neurodegenerative disease of adulthood. Members of our kindreds have not received genetic counseling outside of the research setting. Finally, factors specific to a particular kindred may influence or predict individual responses to genetic testing. © 1994 Wiley‐Liss, Inc.
Repeat length variation in the dopamine D4 receptor gene shows no evidence of association with schizophrenia
Authors: Daniels J. , Williams J. , Mant R. , Asherson P. , McGuffin P. , Owen M. J.
Published: June 2005

The D4 receptor has been shown to exist in several allelic forms (Van Tol et al., Nature 358:149–152, 1992) reflecting variation in the number of 48 base‐pair sequence repeats in the putative cytoplasmic loop. We report a comparison of repeat length variation between schizophrenic patients and controls. Our sample of 106 unrelated schizophrenic cases and 119 controls showed no significant differences in allele or genotype distribution between patients and controls. In particular, we were unable to support the previous observation of an excess of 4‐repeat homozygotes in patients. © 1994 Wiley‐Liss, Inc.
No evidence of association between dopamine D4 receptor variants and bipolar affective disorder
Authors: Lim Lionel C. C. , Nöthen Markus M. , Körner Judith , Rietschel Marcella , Castle David , Hunt Neil , Propping Peter , Murray Robin , Gill Michael
Published: June 2005

Disturbance in the dopamine neurotransmitter system has been implicated in the pathogenesis of affective disorder. In this study, we examine the possibility that functional variants of the recently cloned dopamine D4 receptor gene contribute to the genetic component of manic depression. The polymorphism, a 48 bp tandem repeat coding for part of the third cytoplasmic loop, was detected using a PCR based method. In a first sample of 57 patients and 59 controls, we found allele 7 to be in excess in the patients. In contrast, allele 3 was less frequent in patients. A second, larger sample of 90 patients and 91 controls was utilized to test these hypotheses. Data from the two samples were then pooled together for further analyses. We calculated the power of our samples, and if the frequency of 7 repeat allele obtained from sample 1 is true, i.e., 25% (28/114) for patients and 14% (16/118) for controls, then the power of the combined sample is 62% at 5% (two‐tailed) significance level. However, both observations were not replicated; we therefore conclude that variations in this repeat at the DRD4 gene do not contribute to the genetic component of manic depression. © 1994 Wiley‐Liss, Inc.
Partial trisomy 16p in an adolescent with autistic disorder and Tourette's syndrome
Authors: Hebebrand Johannes , Martin Mathias , Körner Judith , Roitzheim Barbara , de Braganca Katja , Werner Willigis , Remschmidt Helmut
Published: June 2005

A partial trisomy 16p was identified in a 14‐year‐old male adolescent with autistic disorder. He additionally showed complex motor and vocal phenomena, including some simple tics which had first appeared in childhood. Whereas these simple tics were of subclinical significance, an additional diagnosis of Tourette's syndrome (TS) appears justified. The case report illustrates the diagnostic difficulties in assessing psychiatric symptomatology associated with both disorders, especially complex motor and vocal phenomena. The cytogenetic finding is discussed critically in the light of other chromosome abnormalities reported in both TS and autistic disorder. Chromosome 16p should be considered as a candidate region especially for autistic disorder. © 1994 Wiley‐Liss, Inc.
Comparison of schizotypal relatives of schizophrenic versus affective probands
Authors: Lyons Michael J. , Toomey Rosemary , Faraone Stephen V. , Tsuang Ming T.
Published: June 2005

In order to investigate possible heterogeneity in schizotypal personality disorder (SPD), two groups of schizotypals, one related to schizophrenic probands (FSPD) (n = 34) and one related to affective disorder probands (NFSPD) (n = 14), ascertained in the same family study, were compared. The FSPD group had more inadequate rapport; the groups did not differ in the frequency of any other symptoms of SPD. NFSPDs had higher rates of comorbid histrionic PD and a trend for higher rates of impulsive/dramatic cluster PDs. FSPDs had a trend for higher rates of anxiety disorders. There was a higher risk of bipolar disorder in the relatives of NFSPDs and higher risk for anxiety disorders in the relatives of FSPDs. The relatives of NFSPDs had higher rates for histrionic, narcissistic, and atypical PDs and for having at least one PD. © 1994 Wiley‐Liss, Inc.
CODAS syndrome: A new distinct MCA/MR syndrome with radiological changes of spondyloepiphyseal dysplasia. Another case report
Authors: de Almeida José Carlos Cabral , Vargas Fernando Regla , Barbosa‐Neto João G. , Llerena Juan C.
Published: June 2005

We report on a young girl with psychomotor delay, cataracts, abnormally shaped teeth, malformed ears, and radiological findings of spondylo‐epiphyseal dysplasia. The clinical picture resembles the CODAS syndrome described by Shebib et al. [Am J Med Genet 40:88–93, 1991]. © 1995 Wiley‐Liss, Inc.
Deletion of chromosome 3 and a 3;20 reciprocal translocation demonstrated by chromosome painting
Authors: Crispino Beatriz , Cardoso Horacio , Mimbacas Adriana , Méndez Virginia
Published: June 2005

The combined use of high resolution banding and chromosome painting techniques allowed us to identify a reciprocal translocation involving chromosomes 3 and 20 and simultaneous interstitial deletion of chromosome 3 in a patient with several minor anomalies of the face and hands. His karyotype is described as 46,XY,t(3;20) (p14.2;p12.2),del(3)(p11‐p14.1). © 1995 Wiley‐Liss, Inc.
Craniodigital syndromes: Report of a child with Filippi syndrome and discussion of differential diagnosis
Authors: Toriello Helga V. , Higgins James V.
Published: June 2005

We describe a boy with low birth weight, congenital microcephaly, multiple minor facial anomalies, cleft palate, soft tissue syndactyly of fingers and toes, and moderate to severe mental retardation. Literature review suggested 6 possible diagnoses, including Scott craniodigital syndrome, Chitayat syndrome, Filippi syndrome, Zerres syndrome, Kelly syndrome, and Woods syndrome. Each has as part of the phenotype craniofacial anomalies and soft tissue syndactyly of fingers and toes; and superficially, distinction among the 6 may be difficult. However, based on the phenotype analysis we performed, we conclude that our patient has Filippi syndrome, and thus is the first reported case from the United States. © 1995 Wiley‐Liss, Inc.
Interstitial duplication of proximal 22q: Phenotypic overlap with cat eye syndrome
Authors: Knoll J. H. M. , Asamoah A. , Pletcher B. A. , Wagstaff J.
Published: June 2005

We describe a child with downslanting palpebral fissures, preauricular malfunctions, congenital heart defect (total anomalous pulmonary venous return), unilateral absence of a kidney, and developmental delay with an apparent interstitial duplication of proximal 22q. Fluorescent in situ hybridization (FISH) analysis showed duplication of the IGLC locus, and C‐banding of the duplicated region was negative. The duplication appears to involve 22q11.2–q12. Although the child has neither colobomas nor microphthalmia, he shows phenotypic overlap with the cat eye syndrome, which is caused by a supernumerary bisatellited chromosome arising from inverted duplication of the short arm and proximal long arm of chromosome 22. Further molecular studies of this patient should help to define the regions responsible for the manifestations of cat eye syndrome. © 1995 Wiley‐Liss, Inc.