bluuebunny/crossref_metadata_2025 huggingface dataset:
Interstitial deletion 2q14q21
Authors: Frydman Moshe , Steinberger Julia , Shabtai Fiorella , Katznelson Mariassa Bat‐Miriam , Varsano Itzhak
Published: June 2005

A girl with multiple congenital anomalies and a tendency to severe pyogenic infections was found to have an interstitial deletion of chromosome band 2q14‐q21. Unusual facial manifestations included enophthalmos, long philtrum, micrognathia, narrow forehead, prominent glabella, and depressed nasal bridge. Unilateral corneal clouding, with Peters‐like anomaly; agenesis of the corpus callosum; brain atrophy; and heart, kidney, hand, and dermatoglyphic anomalies were additional findings. Eye anomalies were observed in five of 22 patients with deletions of chromosome 2q. In comparing these cases, it seems that deletions of bands 2q21 and 2q31 are variably associated with microphthalmia, corneal clouding, cataracts, and Peters anomaly. Measurement of protein C and interleukin‐1 (IL‐1) did not show a gene dose effect, but the pyogenic infections and low IgA found in this patient may reflect an abnormality of IL‐1 not detectable by our methods.
Inferring mode of inheritance by comparison of lod scores
Authors: Greenberg David A.
Published: June 2005

One usually must assume a mode of inheritance when using lod scores for linkage analysis. In this study, we asked the question, “If one assumed mode of inheritance in a linkage analysis gives a higher lod score than another, does that indicate that the mode of inheritance that led to the higher lod score is more ‘correct’ than the other?”

We simulated data under a variety of penetrances, assuming either dominant or recessive inheritance. We then analyzed those simulated data under the correct mode of inheritance, assuming a range of penetrance values, and under the incorrect model, also assuming a range of penetrance values. We found that, if there was enough information for a maximum lod score of at least 3.0, assuming the correct penetrance value or mode of inheritance in the analysis led to a higher lod score than assuming the incorrect penetrance or the incorrect mode of inheritance. These results cannot yet be generalized outside of the specific modes of inheritance and penetrance combinations that we have modeled. Also, penetrance was modeled as “random.” The effect of “reduced penetrance” caused by other genetic factors has not yet been tested.

We also tested the effect of non‐standard ascertainment on drawing conclusions about mode of inheritance from linkage data. Even when families were ascertained only if the family was multiplex (i.e., more than one affected sib), assuming the correct mode of inheritance gave a higher lod score than assuming the incorrect mode of inheritance.

This method has the promise of both simplifying and expanding the application linkage analysis. The explorations reported here are, however, preliminary, and the method should be used with caution.
Significance of cardiovascular malformations in cystic hygroma: A new interpretation of the pathogenesis
Authors: Miyabara Shinichi , Sugihara Hajime , Maehara Norifumi , Shouno Hideaki , Tasaki Hakaru , Yoshida Keiji , Saito Nakamichi , Kayama Fumiyoshi , Ibara Satoshi , Suzumori Kaoru
Published: June 2005

Fetuses with cystic hygroma or loose skin of the neck were studied chromosomally and phenotypically to clarify the relation between neck abnormality and cardiovascular malformations. Of 12 fetuses, 9 had chromosome abnormalities:4 with 45,X,3 with trisomy 21, one each with trisomy 13, dup 6q. One had normal chromosomes. Two cases, in which chromosome analysis was unsuccessful, were morphologically suspected to be trisomy 13. Nine of the 12 fetuses had either bilateral cystic hygroma of the neck (7 cases) or nuchal bleb (2 cases: trisomy 13 and dup 6q). Two of the 3 remaining cases (trisomy 21) had loose skin of the neck, and one had edematous swelling of the skin of the neck. Except for the last case of trisomy 21, 11 fetuses (91.7%) had severe and/or rare cardiovascular malformations. They were divided into 3 major groups: a) spectrum of hypoplastic left heart syndrome (45,X and dup 6q), b) double outlet right ventricle, agenesis of semilunar valve (trisomy 13), and c) abnormality of atrioventricular orifice or valves (trisomy 21). One fetus with normal chromosomes had persistent left superior vena cava instead of absent right one and calcification of myocardium. Histological observation of edematous skin demonstrated the abnormal distribution of lymph vessels, including their absence. Some cases showed hypoplastic thymus. To integrate the findings of the present study and the descriptions in the literature, a pathogenesis is hypothesized in relation to migration of neural crest cells and extracellular matrix.
Adaptive behavior in the fra(X) syndrome: A longitudinal study in eight patients
Authors: Curfs Paul M. G. , Schreppers‐Tijdink Gerda A. J. , Wiegers Agnes M. , van Velzen Wim , Fryns Jean‐Pierre
Published: June 2005

In this study we investigated the development of adaptive behavior of 8 fragile X [fra(X)] males with special attention to social competence and compared the results with a control group of 8 fra(X) negative males matched for age, level of adaptive functioning, and period of institutionalization.
Molecular‐genetic study of Duchenne and Becker muscular dystrophies: Deletion analyses of 45 Japanese patients and segregation analyses in their families with RFLPs based on the data from normal Japanese females
Authors: Sugino Shigeto , Fujishita Satoshi , Kamimura Naohisa , Matsumoto Tadashi , Wapenaar Martin C. , Deng Han‐Xiang , Shibuya Noritoshi , Miike Teruhisa , Niikawa Norio
Published: June 2005

This study consisted of 1) molecular deletion analyses in patients with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) using the entire cDNA for the DMD gene as hybridization probes, 2) RFLP analyses in a large number of Japanese normal women using 11 DMD‐linked cloned DNAs as probes, and 3) segregation analyses with these RFLP data in 17 DMD families in which prenatal or carrier diagnosis was required. The deletion study showed that 18 (43%) of 42 male DMD patients had a deletion within the DMD gene, while no detectable deletion was found in 3 BMD patients. These deletions were preferentially observed at the 5′ end of the DMD gene, while no deletion was found in the 3′ portion of the gene. Of a total of 15 RFLPs detected with the 11 probes, one was a new RFLP (probe/enzyme: P20/MspI). In 6 RFLPs, the allele frequencies in the Japanese were statistically different from those in the Caucasian. Based on the RFLP data combined with the result of the deletion study, an estimated diagnostic rate for prenatal diagnosis and/or carrier detection in the Japanese DMD families was 63%. The real diagnostic rate obtained from the prenatal and carrier diagnoses, which were practically performed in 17 families, corresponded to the estimation. A protocol useful for the diagnosis in Japanese DMD families is presented.
Mortality rate of amyloidosis in Japan: Secular trends and geographical variations
Authors: Imaizumi Yoko
Published: June 2005

The death rate in Japan from amyloidosis was analyzed using Japanese Vital Statistics for 1969–1985. The amyloidosis death rate has increased gradually year by year for both sexes. The changing patterns in mortality might be explained by a constantly improving ascertainment of amyloidosis. The overall amyloidosis death rate per 100,000 of the population was 0.06 during the period from 1969 to 1978. The geographical variations in the amyloidosis death rate were observed with the highest death rate in Kumamoto and Nagano prefectures (0.29 per 100,000 population) for both sexes during the period from 1979 to 1985. The amyloidosis death rates (per 100,000 population) in 2 large foci of familial amyloidosis polyneuropathy were 9.4 in Ogawa Village, Nagano Prefecture and 3.5 in Arao City, Kumamoto Prefecture during the period from 1979 to 1985. The mean age at death from amyloidosis gradually increased year by year for both sexes, although the age was 11–23 years shorter for males and 20–25 years shorter for females than that of the general population.
Campomelic syndrome: Manifestations in a 20 week fetus and case history of a 5 year old child
Authors: Gillerot Yves , Vanheck Claude‐Annick , Foulon Martine , Podevain Alain , Koulischer Lucien
Published: June 2005

We report on 2 unusual cases of the campomelic syndrome, the first being a fetus in whom the diagnosis was suspected in the 18th week and confirmed sonographically at 20 weeks. The second case concerns a 5 year old 46, XY girl with an exceptional longevity and a relatively favorable evolution.
Down syndrome at birth not detected by first‐trimester chorionic villus sampling
Authors: Bartels Iris , Hansmann Ingo , Holland Ute , Zoll Barbara , Rauskolb Rüdiger
Published: June 2005

A case of a false‐negative first‐trimester diagnosis following chorionic villus sampling is reported that ended with the birth of a child with Down syndrome. Chromosome analysis of 30 metaphases from 24 h‐cultured chorionic villi obtained in week 12 of gestation showed a normal chromosome constitution. However, the newborn showed manifestations of Down syndrome, and 99 of 100 metaphases analysed from cultured lymphocytes showed 47,XY, + 21. The remaining metaphase was normal (46,XY).
Fragile X frequency in a mentally retarded population in Brazil
Authors: Mingroni‐Netto Regina C. , Rosenberg Carla , Vianna‐Morgante Angela M. , de Cássia M. Pavanello Rita
Published: June 2005

Seventy‐five male and 50 female students from 2 special schools for mildly, moderately retarded, or borderline individuals were screened clinically and cytogenetically in order to estimate the contribution of fragile X [fra(X)] syndrome to the cause of mental retardation in Brazil. We found 6 males (8%) from 4 families and 2 unrelated females (4%) with fra(X) chromosomes. One male and one female were isolated cases. The estimated frequency of Martin‐Bell [fra(X)] syndrome among mentally impaired individuals in Brazil was similar to that previously reported in other countries.
Aberrant bronchi and cardiovascular anomalies
Authors: Evans Jane A.
Published: June 2005

In an investigation of malformation associations in consecutive perinatal autopsies, 4 infants were identified as having a displaced or supernumerary bronchus. Each had a different type of bronchial abnormality and 3 had congenital heart defects and other malformations.

Review of the literature found 38 other cases of aberrant bronchi with additional defects, especially cardiovascular or costovertebral anomalies. Structural cardiac defects were more common in patients with supernumerary tracheal bronchi (67%) than in those with displaced tracheal bronchi (27%) or bronchoesophageal connections (23%). There was also a strong negative association (P=0.01) of cardiovascular and costovertebral defects unless multiple anomalies were present.

The combinations of anomalies seen appear to reflect relatively specific developmental field defects affected both by the spatial relationships of organs near the developing foregut and by temporal sequence. Recognition of these patterns has clinical and embryological importance. Aberrant bronchi should be considered when children with cardiac defects or multiple anomalies such as the VACTERL association have unexplained respiratory symptoms and surgeons planning to treat such bronchial abnormalities should be aware of the high frequency of abnormal vessels in these cases.
New manifestations of Neu‐Laxova syndrome
Authors: Naveed  , Manjunath C. S. , Sreenivas Vijaya
Published: June 2005

We report on a newborn boy with Neu‐Laxova syndrome and spina bifida, bilateral cryptorchidism, and shallow orbital cavities. Asso‐ciation of these manifestations in Neu‐Laxova syndrome is the first to be reported in the literature. This is the first report of Neu‐Laxova syndrome from India.
Somatic development in cleidocranial dysplasia
Authors: Jensen Birgit Leth
Published: June 2005

As part of a more comprehensive investigation of general and craniofacial development in cleidocranial dysplasia (CCD), the present study describes general somatic development and analyzes longitudinal growth of 17 patients (seven males, ten females, aged 5–46 years) with CCD. Eleven were followed longitudinally. Data included family history, anthropometric measurements, and radiographs of the right hand and forearm. Height and radius length were significantly decreased, being most pronounced in females. The longitudinal growth data showed growth retardation and slightly retarded skeletal maturity throughout childhood. Metacarpophalangeal pattern profile analysis demonstrated great variation in bone lengths, presumably resulting from extra epiphyses in the 2nd and 5th metacarpals and from multiple cone‐shaped epiphyses. Findings of the present study support the view that CCD is a generalized skeletal dysplasia.
Ectro‐amelia syndrome associated with an interstitial deletion of 7q
Authors: Morey Martha A. , Higgins Rodney R.
Published: June 2005

We describe a premature male infant with an interstitial deletion of 7q [46, XY, del(7) (pter→ q21.3::q31.3→qter]. Manifestations include absence of lower limbs, unilateral ectrodactyly, facial anomalies, gingival hyperplasia, feeding problems, and atrial septal defect. Chromosome 7 deletions of the q21.3→q31.3 region are reviewed with emphasis on limb anomalies.
Prenatal diagnosis of X‐linked hypohidrotic ectodermal dysplasia by linkage analysis
Authors: Zonana Jonathan , Schinzel Albert , Upadhyaya Meena , Thomas Nicholas S. T. , Anton‐Lamprecht Ingrun , Harper Peter S.
Published: June 2005

Prenatal diagnosis of X‐linked hypohidrotic ectodermal dysplasia was previously performed by the direct histological analysis of fetal skin obtained by late second trimester fetoscopy. The recent gene mapping of the locus for the disorder to the region of Xq11‐21.1 now permits the indirect prenatal diagnosis of the disorder by the method of linkage analysis, based on closely linked marker loci, during the first trimester of pregnancy. We report the prenatal diagnosis of a male fetus with a high probability of the disorder by a linkage analysis utilizing restriction fragment length polymorphisms at the DXS159, PGK1, and DXS72 loci, from a DNA sample obtained by a chorionic villus biopsy at 9 weeks gestation. After further counseling, the pregnancy was terminated but the diagnosis could not be confirmed by histological analysis, even though analysis of skin samples by light and electron microscopy showed lack of hair germs, primary dermal ridges, and sweat gland primordia, due to the early developmental stage of the fetus. The use of DNA‐based linkage analysis now offers the opportunity for an earlier diagnosis of X‐linked hypohidrotic ectodermal dysplasia by a method other than fetal skin sampling. However, families must also fully understand the present limitations of the method prior to undertaking the procedure.
Rett phenotype with X/autosome translocation: Possible mapping to the short arm of chromosome X
Authors: Journal Hubert , Melki Judith , Turleau Catherine , Munnich Arnold , de Grouchy Jean
Published: June 2005

Rett syndrome (RS) was diagnosed in a girl with a t(X;22)(p11.22;p11). This translocation was also present in her unaffected mother and her sister affected by a neurological disorder compatible with a “forme fruste” of RS. Different etiological mechanisms are considered: gene disruption, X inactivation disturbance, metabolic interference. Whatever this may be, the localization of a RS related gene to the short arm of chromosome X is likely.
Chromosome abnormalities in older women by maternal age: Evaluation of regression‐derived rates in chorionic villus biopsy specimens
Authors: Hook Ernest B.
Published: June 2005

Maternal age‐specific rates of chromosome abnormalities in women undergoing chorionic villus sampling (CVS) were evaluated. These were rates derived from regression equations of the form rate = 1n(b [age] + c) where age varied from 35 to 48 years; and b and c are parameters. For Down syndrome (47, + 21), b = 0.29 and c = −15.53; for other nonmosaic abnormalities, b = 0.25 and c = −14.11; and, for all abnormalities, b = 0.27 and c = −14.22. The predicted rates per 1,000 varied, respectively, from 4.2, 4.6, and 8.8 at age 35 years to 180.0, 120.0, and 300.0 at age 48 years. The predicted numbers of abnormalities were compared with those observed in an overlapping data set reported in the literature. For 47, + 21, the ratio of observed (O) to expected (E) numbers was 54/56.4 = 0.96, suggesting that these rates are at least not grossly erroneous. For non‐47, + 21 chromosome abnormalities, the ratio of O to E was 66/51.1 = 1.29. The possibility of geographic variation in rates of non‐47, + 21 chromosome abnormalities cannot be dismissed. Finally, if 1) the regression derived rates are correct, 2) there is no difference in selective loss of chromosome abnormalities between younger and older mothers, and 3) the ratio of rates at ages 35 and 40 years to those in the women of all ages are the same for all abnormalities at CVS as for 47, + 21 in live births, then the proportion of all women with viable conceptuses at time of CVS who have an embryo or fetus with cytogenetic abnormality is 3.8–4.4 per 1,000 conceptuses.
Prospective study of amniocentesis performed between weeks 9 and 16 of gestation: Its feasibility, risks, complications and use in early genetic prenatal diagnosis
Authors: Elejalde B. Rafael , de Elejalde Maria M. , Acuña Juan M. , Thelen Diana , Trujillo Carlos , Karrmann Michael
Published: June 2005

This paper demonstrates that the outcome of amniocenteses performed between the 9th and the 14th weeks is similar to that of amniocenteses performed between the 15th and 20th weeks. We have performed and prospectively followed 615 amniocenteses between the 9th and 16th weeks of gestation. The outcome, risks, and complications are similar to those of amniocenteses at the usual time (after 15 weeks) and to the other groups of early amniocentesis (before 15 weeks). Early amniocentesis differs from amniocentesis at the usual time in that it carries higher rates of fetal losses and of amniotic fluid leakage, more confined cytogenetic abnormalities, and an increased number of patients who have the procedure postponed. Two cultures (0.32%) failed to produce results, 595 (96.7%) samples were obtained at the first tapping, 20 (3.3%) at the second attempt. α‐Fetoprotein levels reach their maximum at 13 weeks. Amniocenteses between 15 and 16 weeks (293, or 47%) constitute the control group, those between 9 and 14 weeks (322) the experimental group. Early amniocentesis appears to be a safe early genetic prenatal diagnosis technique, an alternative to chorionic villi sampling.
Preimplantation sexing and diagnosis of hypoxanthine phosphoribosyl transferase deficiency in mice by biochemical microassay
Authors: Monk Marilyn , Handyside Alan , Muggleton‐Harris Audrey , Whittingham David
Published: June 2005

Hypoxanthine phosphoribosyl transferase (HPRT)‐deficient male embryos derived from heterozygous (carrier) female mice were diagnosed by biochemical microassay of X‐chromosome‐coded HPRT activity in a single cell taken from the 8‐cell embryo or in 5–10 cells sampled from the blastocyst. In the latter procedure, carrier female blastocysts could also be distinguished from affected males, and normal males and females, as having intermediate HPRT activity in the sampled trophectoderm cells.

During the assay procedures, the operated preimplantation embryos were cultured. They were then transferred, in batches as diagnosed, to recipient females. The resulting fetuses were sexed by gonad morphology and assayed for HPRT activity. All those identified as HPRT‐negative embryos by biopsy at the 8‐cell or blastocyst stages were indeed HPRT‐negative males. The heterozygous females were also correctly identified by the trophectoderm biopsy procedure.

The sex of an embryo can also be diagnosed by HPRT activity dosage in a single blastomere taken from 8‐cell embryos from a normal mating and cultured for 12 hours before assay. Both X chromosomes are active in female morulae and the blastomeres sampled from female preimplantation embryos have twice the X‐coded HPRT activity compared to those from the male embryos. The accuracy of this procedure for sexing was again verified by transfer of the putative male and putative female embryos into recipient females.

The diagnoses of HPRT deficiency or sex in the biopsied samples from preimplantation embryos were sufficiently rapid so that freezing of the embryos before transfer was not necessary.
Mirror polydactyly: Pathogenesis based on a morphogen gradient theory
Authors: Viljoen Denis L. , Kidson Susan H.
Published: June 2005

We report on an infant with 7 toes of the left foot in a mirror configuration in association with ipsilateral duplication of the calcaneus and fibula, tibial aplasia, femoral hypoplasia, and a teratomatous sacrococcygeal tumour. The possible pathogenetic mechanisms leading to this limb abnormality are discussed with special emphasis on a field morphogen gradient hypothesis.
A ring X chromosome, 46,Y,r(X)(p22.33q28), as a cause of extreme short stature in a male
Authors: Ogata Tsutomu , Matsuo Nobutake , Shimizu Nobuyoshi
Published: June 2005

We describe a 15 10/12‐year‐old boy (Tanner stage 4, peak growth velocity 7 cm/year) with a ring X chromosome who presented with extreme short stature (mean ‐ 5.3 SD) as the sole recognizable abnormality. His chromosome constitution was determined to be 46,Y, r(X) (p22.33q28) in 174 of 182 peripheral blood cells and in 35 skin fibroblasts. Of the remaining eight peripheral blood cells, five had a dicentric double‐size ring and three had a smaller ring. Other laboratory studies for short stature were noncontributory. We suspect that the ring's specific behavior in mitosis or its effect on expression of the statural determinant on the X chromosome short arm may be responsible for short stature in this patient.
Congenital hypoplastic (Diamond‐Blackfan) anemia in seven members of one kindred
Authors: Viskochil David H. , Carey John C. , Glader Bertil E. , Rothstein Gerald , Christensen Robert D.
Published: June 2005

Congenital hypoplastic (Diamond‐Blackfan) anemia is a rare macrocytic anemia, generally presenting during infancy or childhood. The condition usually occurs sporadically or in a pattern consistent with autosomal recessive inheritance, although autosomal dominant transmission has been proposed in some kindreds. We report the largest known kindred of congenital hypoplastic anemia, with at least 7 affected individuals over 3 generations, and propose that studies of this kindred may be useful for identifying the mechanism by which their genetic abnormality results in congenital hypoplastic anemia. Erythropoietic investigations on relatives show no inhibitors of erythropoiesis in serum, T‐lymphocytes, or macrophages. Their erythroid progenitor cells (CFU‐E and BFU‐E) were generally quantitatively normal, and were capable of rapid proliferation, as judged by cellcycle shortening. However, their erythroid progenitors displayed a relative insensitivity to recombinant erythropoietin, and produced relatively few normoblasts per erythroid progenitor cell. We propose that these and subsequent studies may be helpful in selecting candidate genes responsible for the molecular defect in this kindred.
Distal deletion of the short arm of chromosome 6
Authors: Zurcher Vickie L. , Golden Wendy L. , Zinn Arthur B.
Published: June 2005

We report on a patient with deficiency of distal 6p and compare the clinical and cytogenetic findings in this child with those of three previously reported patients who had similar deletions. Distal del(6p) appears to be associated with a relatively non‐specific phenotype, with the possible exception of unusual congenital eye findings. This apparent association of congenital eye defects with distal del(6p) was supported by comparison with patients having other deletions of chromosome 6, particularly those with ring chromosome 6.
Proteus syndrome: Course of a severe case
Authors: Malamitsi‐Puchner Ariadne , Dimitriadis Dimitris , Bartsocas Christos , Wiedemann H.‐R.
Published: June 2005

We report on the course of a 4½‐year‐old boy with Proteus syndrome who was first described 3 years ago. Details are given on the phenotypic changes, the complications of corrective surgery on tissue overgrowth, and the development of a mesothelioma of the tunica vaginalis of the testis.
Chromosome 7 abnormalities in parents of children with holoprosencephaly and hydronephrosis
Authors: Lurie I. W. , Ilyina H. G. , Podleschuk L. V. , Gorelik L. B. , Zaletajev D. V.
Published: June 2005

At least nine cases of holoprosencephaly (HPE) found in patients with confirmed loss of 7q34→7qter or 7q36→7qter have been reported in the literature. In the present report, balanced rearrangements involving chromosome 7q [inv(7)(p22.1q34) and t(4;7)(q31;q36)] were shown in two mothers examined after the birth of their non‐karyotyped infants with HPE and hydronephrosis. In both cases, del(7q) was the most probable imbalance. The available data confirm the association between HPE and del(7q). Predominance of cyclopia and cebocephaly, the severest forms of HPE, suggests that del(7q) may be an important factor in arresting prosencephalon development at the earliest stages.
Cytogenetic and molecular study of the Angelman syndrome
Authors: Imaizumi Kiyoshi , Takada Fumio , Kuroki Yoshikazu , Naritomi Kenji , Hamabe Junichi , Niikawa Norio
Published: June 2005

Six patients, including two sibs, with Angelman syndrome (AS; three females and three males, aged 11 to 18 years) were studied cytogenetically. Molecular analysis was also performed. Using high‐resolution banding technique, we detected a microdeletion in the proximal region of chromosome 15q in four cases. The deleted segment was heterogenous between these patients, and the common deleted region appeared to be 15q11.2. Four patients with deleted 15q were all sporadic cases, whereas in the sib cases we could not detect a visible deletion in the long arm of chromosome 15. However, there was no clinical difference between sporadic cases and sib cases. Densitometric analysis of autoradiographic bands of Southern hybridization using two DNA segments, pML34 and pTD3‐21, as probes demonstrated that two patients had only one copy for each of the probes. In the remaining four patients, including the sibs, two copies of each sequence were retained. The probes used here detect a molecular deletion in most Prader‐Willi syndrome patients. Thus the segment causing AS is localized adjacent to the critical segment of Prader‐Willi syndrome. There seemed to be heterogeneity for the molecular deletion within AS individuals.
Prader‐Willi syndrome: Current understanding of cause and diagnosis
Authors: Butler Merlin G.
Published: June 2005

Prader‐Willi syndrome (PWS) is characterized by hypotonia, obesity, hypogonadism, short stature, small hands and feet, mental deficiency, a characteristic face, and an interstitial deletion of the proximal long arm of chromosome 15 in about one‐half of the patients. The incidence is estimated to be about 1 in 25,000, and PWS is the most common syndromal cause of human obesity. DNA abnormalities, usually deletions or duplications of chromosome 15, have been identified in individuals with PWS with or without recognizable chromosome 15 deletions. Paternal origin of the chromosome 15 deletion by cytogenetic and DNA studies has been found in nearly all PWS individuals studied. No cytogenetic evidence for chromosome breakage has been identified, although an environmental cause (e.g., paternal hydrocarbon‐exposed occupations) of the chromosome 15 abnormality has been proposed. PWS patients with the chromosome 15 deletion are more prone to hypopigmentation compared with PWS individuals with normal chromosomes, but no other clinical differences are consistently identified between those with and without the chromosome deletion. Anthropometric, dermatoglyphic, and other clinical findings indicate homogeneity of PWS patients with the chromosome deletion and heterogeneity of the nondeletion patients. A review of our current understanding of the major clinical, cytogenetic, and DNA findings is presented, and clinical manifestations and cytogenetic abnormalities are summarized from the literature.
Comparison of the 15q deletions in Prader‐Willi and Angelman syndromes: Specific regions, extent of deletions, parental origin, and clinical consequences
Authors: Magenis R. E. , Toth‐Fejel S. , Allen L. J. , Black M. , Brown M. G. , Budden S. , Cohen R. , Friedman J. M. , Kalousek D. , Zonana J. , Lacy D. , Lafranchi S. , Lahr M. , Macfarlane J. , Williams C. P. S.
Published: June 2005

It has recently been shown that apparently similar deletions of chromosome 15q occur commonly in the Prader‐Willi and Angelman syndromes. The distinctness of the syndromes suggests that the deletions are not identical. To address this possibility, the specific bands involved and the sizes of the deletions were compared in seven patients with Prader‐Willi syndrome and 10 patients with Angelman syndrome using high‐resolution G‐, Q‐, and fluorescent R‐banding techniques. The parental origin of the nine cases of Angelman syndrome for which parents were available for study was determined. The same proximal band was deleted (q11.2) in both syndromes. In general, the deletion in patients with Angelman syndrome was larger, though variable, and included bands q12 and part of q13. All of the studied deletions in patients with Angelman syndrome were of maternal origin. This contrasts with the predominant paternal origin of the deletion in patients with Prader‐Willi syndrome. Two possible reasons for these observations are postulated: 1) the deleted regions are different at the cytologic and/or molecular level because of different exchange points in meiosis in males and females or to different mechanisms of breakage in males and females, resulting in differing breakpoints; 2) the deleted regions are essentially the same, but differential expression of the genes in the homologous chromosome 15 has occurred (imprinting).
Maternal origin of 15q11–13 deletions in Angelman syndrome suggests a role for genomic imprinting
Authors: Williams C. A. , Zori R. T. , Stone J. W. , Gray B. A. , Cantu E. S. , Ostrer H.
Published: June 2005

Six persons with the classical Angelman syndrome (AS) phenotype and de novo deletions of chromosome 15q11‐q13 were studied to determine the parental origin of the chromosome deletion. Four of the 6 patients had informative cytogenetic studies and all demonstrated maternal inheritance of the deletion. These findings, together with other reported cases of the origin of the chromosome 15 deletion in AS, suggest that deletion of the maternally contributed chromosome leads to the AS phenotype. This contrasts with the Prader‐Willi syndrome (PWS) in which a similar deletion of the paternally contributed chromosome 15 is observed. In deletion cases, a parental gamete effect such as genomic imprinting may be the best model to explain why apparently identical 15q11‐q13 deletions may develop the different phenotypes of AS or PWS.
Segregation distortion in inheritance of progressive rod cone degeneration (prcd) in Miniature Poodle dogs
Authors: Acland Gregory M. , Halloran‐Blanton Susan , Boughman Joann A. , Aguirre Gustavo D.
Published: June 2005

Segregation distortion was observed in inheritance of progressive rod–cone degeneration (prcd) in a colony of Miniature Poodle dogs. Breeding results, from both retrospective records and prospectively planned matings, were classified into five mating types: (1) affected to affected, (2) homozygous normal sire to any dam, (3) heterozygous to heterozygous, (4) heterozygous sire to affected dam, and (5) affected sire to heterozygous dam. For all but the last category, results were in accord with mendelian expectations for autosomal‐recessive inheritance. However, litters of mating type 5 had fewer affected pups (20/77) than expected. The observed segregation ratio for this mating type (0.26) was significantly (P<0.001) less than the expected (0.50). The segregation distortion could not be accounted for by either pre‐ or postnatal loss of affected pups, as litter size and litter survivability were uniform among litters of different mating types. Either the prcd locus, or a linked locus, would appear to influence either gametic or zygotic fitness in the heterozygous mother. Comparison is drawn to the inheritance of retinitis pigmentosa in humans, in which decreased segregation ratios are also recognized.
Adenine nucleotides, serotonin, and aggregation properties of platelets of blue foxes (Alopex lagopus) with the Chediak‐Higashi syndrome
Authors: Sjaastad Øystein V. , Blom Anne K. , Stormorken Helge , Nes Norodd
Published: June 2005

Bleeding times, concentrations of serotonin in whole blood, and concentrations of adenine nucleotides as well as aggregation properties of platelets were examined in 18 blue foxes with Chediak‐Higashi–like syndrome (CHS) and 16 controls. A claw of each ketamine‐sedated fox was cut until bleeding started and the bleeding time was recorded as the time from the first to the last drop. The bleeding time was greatly increased in CHS foxes. Platelet counts of CHS foxes were normal, but aggregation induced by adenosine diphosphate (ADP), serotonin, collagen, and arachidonate was impaired. Adrenaline and serotonin potentiated the aggregatory effect of ADP on control as well as on CHS platelets. The mean concentration of ADP in CHS platelets was about one‐third that in controls, whereas adenosine triphosphate (ATP) was approximately one‐half that in controls. Serotonin could not, in most cases, be detected in blood of CHS foxes. These findings suggest that the prolonged bleeding time in the CHS foxes is, at least partly, due to a storage pool deficiency. The drastically reduced, and in some cases absent, aggregation of CHS platelets in response to arachidonate suggests that defective arachidonate metabolism contributes to the impaired hemostasis.
Familial renal hypophosphatemia, minor facial anomalies, intracerebral calcifications, and non‐rachitic bone changes: Apparently new syndrome?
Authors: Chitayat David , McGillivray Barbara C. , Rothstein Ralph , Flodmark Olof , Priddy Robert W. , Ebelt Volker J. , Lirenman David S. , Hall Judith G.
Published: June 2005

We report on two brothers with renal hypophosphatemia, intracerebral calcifications, minor facial anomalies, and short distal phalanges. The children presented with recurrent dental abscesses; one had premature closure of the anterior fontanelle. Biochemical findings included hypophosphatemia and elevated serum alkaline phosphatase with normocalcemia. Blood levels of parathyroid hormone, 1,25(OH)2 and 25(OH) vitamin D levels were normal; TRP (the fractional tubular reabsorption of PO4) and TmP/GFR (the tubular maximum rate of PO4 reabsorption in relation to GFR) were low. Both parents had a normal serum phosphate and brain CT scan without evidence of calcifications.

This apparently new syndrome of renal hypophosphatemia associated with intracerebral calcifications appears to be inherited as either an autosomal recessive or an X‐linked trait.
Myelodysplasia and leukemia syndrome with monosomy 7: A genetic perspective
Authors: Gilchrist D. M. , Friedman J. M. , Rogers P. C. J. , Creighton S. P.
Published: June 2005

Acquired monosomy 7 is a frequent finding in myelodysplastic syndromes, including acute myelogenous leukemia. A subset of these patients has been described with an apparently distinct condition: myelodysplasia and leukemia syndrome with monosomy 7 (MLSM7). We report 2 brothers, 3 and 5 years of age, with MLSM7 and review other reports of familial occurrence. Genetic factors appear to be important in the cause of MLSM7, but the reported families do not fit neatly into any monogenic pattern. Recognition of the frequently familial nature of this condition requires hematological evaluation and genetic counseling for the families of patients with MLSM7.
Severe postaxial acrofacial dysostosis: An anatomic and angiographic study
Authors: Rodríguez José Ignacio , Palacios José
Published: June 2005

We describe a severe case of postaxial acrofacial dysostosis syndrome [POADS] or Geneée‐Wiedemann syndrome in a stillborn female. The report includes an arteriographic and anatomic study of the limbs. Previously unreported findings such as hypoplasia of the femora, ossification defect of the ischium and pubis, bilobed tongue, and lung hypoplasia were noted. This case documents further variability in the POADS or Genée‐Wiedemann syndrome.
Mosaicism in Pallister i(12p) syndrome
Authors: Wenger Sharon L. , Boone Leslie Y. , Steele Mark W.
Published: June 2005

The clinical diagnosis of Pallister syndrome in a 1‐day‐old white boy was confirmed by the presence of i(12p) in 100% of cells on direct bone marrow analysis. This is the second Pallister syndrome case in which cytogenetic diagnosis was made in bone marrow cells during the neonatal period. Other tissues analyzed in our patient included peripheral blood PHA‐stimulated cultured lymphocytes and postmortem skin and lung cultured fibroblasts with 3%, 98.5%, and 97.5% of cells containing the i(12p), respectively. Serial skin fibroblast cultures re‐established from frozen cells were analyzed sequentially over time for the isochromosome. There was slight reduction in the proportion of i(12p) cells until passage 15 with plateauing of the proportion of i(12p) cells at about 80% until culture senescence. Our review of such cytogenetic analyses suggests that in vivo and perhaps also in vitro isochromosome loss best explains the intra‐ and inter‐tissue specific chromosomal mosaicism in the i(12p) syndrome. In any event, our results indicate that confirmation of the diagnosis in the neonatal period is possible by direct cytogenetic analysis of bone marrow.
De novo inverted interstitial (“mirror”) duplication of chromosome 8(q13→q24.1) in a liveborn male
Authors: Donnenfeld Alan E. , Coyne Michael D. , Beauregard Laurent J.
Published: June 2005

We report on a newborn boy with a de novo inverted interstitial duplication of chromosome 8(q13→q24.1). This form of cytogenetic abnormality, in which a mirror image interstitial duplication has occurred, is exceedingly rare. Review of the literature and mechanisms to explain the origin of this type of chromosome aberration are presented. A review of the findings from individuals with partial dup(8q) demonstrate remarkable similarity to the infant we describe.
Alagille syndrome (arteriohepatic dysplasia) and del(20)(p11.2)
Authors: Legius Eric , Fryns Jean‐Pierre , Eyskens Benedict , Eggermont Ephren , Desmet Valeer , de Bethune Guy , Van den Berghe Herman
Published: June 2005

We report on a boy with Alagille syndrome. Chromosome analysis on a peripheral blood lymphocyte culture showed a de novo deletion of the short arm of chromosome 20 with a 46,XY,del(20)(p11.2) chromosome constitution. This is the second report of a del(20p) in a patient with Alagille syndrome. The possible localisation of this autosomal dominant syndrome on 20p is discussed.
Trichothiodystrophy, mental retardation, short stature, ataxia, and gonadal dysfunction in three Moroccan siblings
Authors: Przedborski Serge , Ferster Alina , Goldman Sylvie , Wolter Renée , Song Micheline , Tonnesen Tonne , Pollitt Rodney J. , Vamos Esther
Published: June 2005

Three sibs, a boy and two girls, born to Moroccan consanguineous parents, were affected with a syndrome characterized by brittle hair, mental retardation, short stature, ataxia, and gonadal dysfunction. The hair in these three patients displayed the morphological and biochemical hallmarks of trichothiodystrophy (TTD). Gonadal function tests showed abnormal gonadotropic responses to LHRH, consistent with delayed puberty in the male and ovarian failure in both females. Comparison with previously reported cases of TTD associated with mental retardation suggests genetic heterogeneity, although specific biochemical markers are needed in order to answer this question.
Distal phalangeal hypoplasia in children with prenatal phenytoin exposure: Results of a controlled anthropometric study
Authors: Gaily Eija
Published: June 2005

Phalangeal and metacarpal bone length was measured from hand radiographs in 111 children of epileptic mothers and 96 control children of nonepileptic mothers. Seventy‐six children of the study group had been exposed to phenytoin in the first 20 weeks of pregnancy, 21 had been exposed to other antiepileptic drugs excluding phenytoin, and 14 had not been exposed. Distal phalangeal lengths were significantly reduced in phenytoin‐exposed children. The second and fifth digits were most affected. Phenytoin exposure was associated with a significantly elevated prevalence (11%) of radiologically defined distal phalangeal hypoplasia. The subgroup of children exposed to phenytoin levels over 40 μmol/I showed more prominent effects than did the subgroup exposed to lower or unknown concentrations. These results confirm that early fetal exposure to phenytoin decreases distal phalangeal size, as suggested by several previous studies relying on clinical examination only. Distal phalangeal hypoplasia was not accompanied by other serious abnormalities.
Comparison of direct and indirect methods of carrier detection in an X‐linked disease
Authors: Koeberl Dwight D. , Bottema Cynthia D. K. , Sommer Steve S.
Published: June 2005

For a severe X‐linked disease such as hemophilia B, unrelated patients generally will have different mutations. Restriction fragment length polymorphisms (RFLPs) have been used to perform carrier testing in an indirect manner by following the segregation of the disease allele through the pedigree. However, this approach requires family participation and suffers from multiple levels of uncertainty. We have applied the direct sequencing technique of genomic amplification with transcript sequencing (GAWTS) to direct carrier testing. Here we compare direct and RFLP‐based testing in two families with hemophilia B. A total of 22 at‐risk females was diagnosed by direct testing, whereas only 11 females could be diagnosed by standard RFLP analysis. The superior accuracy and greater conceptual simplicity of direct testing is demonstrated and some commonly overlooked uncertaintics in RFLP analysis are highlighted.
Apparently nonmosaic trisomy 22: Clinical report and review
Authors: Sundareshan T. S. , Naguib K. K. , Al‐Awadi S. A. , Redha M. A. , Hamoud M. S.
Published: June 2005

We report on apparently nonmosaic trisomy 22 in a liveborn girl with multiple congenital anomalies. The abnormalities were growth retardation; microcephaly; hypertelorism; epicanthic folds; anti‐mongoloid slant; apparently low‐set, malformed ears; highly arched, cleft palate; short webbed neck; and hypoplastic nails. The extra 22 was found to be of maternal origin by chromosome polymorphism.
The UCLA–university of Utah epidemiologic survey of autism: Genealogical analysis of familial aggregation
Authors: Jorde L. B. , Mason‐Brothers A. , Waldmann R. , Ritvo E. R. , Freeman B. J. , Pingree C. , McMahon W. M. , Petersen B. , Jenson W. R. , Mo A.
Published: June 2005

To assess familial aggregation of autism, 86 autistic subjects were linked to the Utah Genealogical Database. Kinship coefficients were estimated for all possible pairs of autistic subjects and then averaged. Fifty replicate sets of matched control subjects (86 members in each set) were drawn randomly from the database, and the average kinship coefficient was computed for all possible pairs of individuals in each set. The average kinship coefficient for the autistic subjects was approximately 1/1,000, while the average kinship coefficients for the 50 control groups ranged from 4/100,000 to 1.6./10,000. These results indicate a strong tendency for autism to cluster in families. When kinship was analyzed by specific degrees of relationship, it was shown that the familial aggregation of autism is confined exclusively to sib pairs and does not extend to more remote degrees of relationship. This finding indicates that a single‐gene model is unlikely to account for most cases of autism.
Midtrimester diagnosis and anomalies in the dup(22q) syndrome: Correlation of aneuploidy with low maternal serum alpha‐fetoprotein and oligohydramnios
Authors: Johnson Mark Paul , Greb Anne , Goyert Gregory , Drugan Arie , Qureshi Faisal , Sacks Alan J. , Evans Mark I.
Published: June 2005

We present the first reported case of prenatally diagnosed dup(22q) syndrome in a 20‐year‐old woman referred for genetic counseling because of a low maternal serum alphafetoprotein value. An ultrasound study at 22 weeks demonstrated oligohydramnios, intrauterine growth retardation, multiple facial malformations, and a cardiac defect. Fetal karyotype was 46, XYdup(22)(pter→q13:: q12→qter) by amniocentesis. Necropsy following pregnancy termination confirmed all prenatally delineated anomalies. Comparison is made with the complete and partial proximal dup(22q) syndromes. We emphasize the correlation between aneuploidy and the presence of low maternal serum alpha‐fetoprotein, oligohydramnios, and midgestational intrauterine growth retardation.
Evidence for a major gene in familial anencephaly
Authors: Shaffer Lisa G. , Marazita Mary L. , Bodurtha Joann , Newlin Anna , Nance Walter E.
Published: June 2005

A 21‐year‐old white woman sought counseling after the birth of two consecutive anencephalic male fetuses with complete rachischisis and discordant renal dysplasia. The presence of parental consanguinity prompted reconsideration of recessive inheritance. The segregation ratio from 23 additional consanguineous cases was compared with that observed in 294 presumably nonconsanguineous families previously reported. Using classical segregation analysis, the segregation ratios in the non‐sporadic cases were consistent with a major autosomal recessive locus in both populations.
Neonatal‐onset panhypopituitarism in a girl with Brachmann‐De Lange syndrome
Authors: Tonini G. , Marinoni S.
Published: June 2005

We report on a girl with recurrent hypoglycemia since age 2 days and severe impairment of physical and neurological development. Panhypopituitarism was recognized at age 5 months. The diagnosis of Brachmann‐De Lange syndrome (BDLS) was also made. Replacement therapy has avoided further episodes of hypoglycemia, improved growth, and allowed partial psychomotor catch‐up.

Though we are not aware of any other report of panhypopituitarism in patients with BDLS, we suggest that hormonal derangement may play a role in the manifestations of this syndrome.
The thoracoabdominal syndrome (TAS): A new X‐linked dominant disorder
Authors: Carmi R. , Barbash A. , Mares A. J.
Published: June 2005

We report on a family with a previously undescribed malformation syndrome. The syndrome is composed of diaphragmatic and ventral herniae, hypoplastic lung, and associated cardiac anomalies. The relative number of affected males and females and appreciably severer manifestations in males suggest an X‐linked dominant inheritance.
Another model for the inheritance of Rett syndrome
Authors: Bühler Erica M. , Malik Naseem J. , Alkan Muallâ
Published: June 2005

The fact that probably less than 1% of Rett syndrome cases are familial speaks in favor of a spontaneous mutation as the most common cause of Rett syndrome. However, the few familial cases (about 10) described in the literature, the elevated consanguinity rate in parents of Rett patients (2.4% vs. 0.5%), and the existence of “formes frustes” in relatives of Rett girls, suggest that inheritance must exist. A model based on a hypothetical form of inheritance, namely allelic and non‐allelic metabolic interference, fits almost all available data, as well as the exclusive occurrence in females without increased abortion rate.
Tetrasomy 18p in a child with trisomy 18 phenotype
Authors: Singer T. S. , Kohn G. , Yatziv S.
Published: June 2005

We report on a patient with trisomy 18 syndrome and tetrasomy 18p. The case indicates that the presence of an isochromosome i(18p) can mimic complete trisomy 18 syndrome.