bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic contributions to quantitative lipoprotein traits associated with coronary artery disease: Analysis of a large pedigree from the Bogalusa heart study
Authors: Heiba Ibrahim M. , DeMeester Cynthia A. , Xia Yu‐Rong , Diep Anh , George Varghese T. , Amos Christopher I. , Srinivasan Sathanur R. , Berenson Gerald S. , Elston Robert C. , Lusis Aldons J.
Published: June 2005

A pedigree of a large family with high prevalence of heart disease is subjected to association and sib‐pair linkage analysis to investigate the role of 5 candidate genes in the regulation of lipoprotein metabolism and the development of coronary artery disease. At the 5% nominal significance level, the apolipoprotien B locus (APOB) was found to be linked to high‐density lipoprotein cholestrol level (HDL‐C), low‐density lipoprotein cholestrol level (LDL‐C), the ratio HDL‐C/LDL‐C, and apolipoprotein AI level times this ratio (apoAI × LDL‐C/HDL‐C). APOB (PvuII) was strongly associated with apolipoprotein B levels (apoB) (P = 0.006) and the VNTR region of the APOB locus showed highly significant association between allele 7 and low triglyceride levels (P = 0.004). No significant linkage results were found with cholesterol ester transfer protein (CETP). At the 1% nominal significance level, CETP [TaqI(B)] showed significant association with LDL‐C, apoB, and HDL‐C/LDL‐C. There was significant linkage of lipoprotein lipase (LPL) with very‐low‐density lipoprotein cholestrol and the ratio apoAI/HDL‐C, and strong association results between LPL (HindIII) and triglyceride levels (P = 0.005). At the 5% nominal significance level, haptoglobin (HPA) was associated with HDL‐C, HDL‐C/LDL‐C, apoAI/HDL‐C and apoAI × LDL‐C/HDL‐C. The apolipoprotein AI locus did not show any significant linkages or associations. The study thus indicated that genetic variation of APOB, LPL, CETP, and lecithin cholestrol acyl transferase (which is linked to HPA and CETP) may play an important role in the regulation of lipoprotein metabolism and could contribute to the risk of coronary artery disease. © 1993 Wiley‐Liss, Inc.
Two additional cases of the Ohdo blepharophimosis syndrome
Authors: Maat‐Kievit Anneke , Brunner Han G. , Maaswinkel‐Mooij Petra
Published: June 2005

Two additional cases of the Ohdo blepharophimosis syndrome are described and compared to the 5 patients previously reported. Blepharophimosis, ptosis, dental hypoplasia, mental retardation, and deafness can be considered as common manifestations of the syndrome. Male patients show cryptorchidism and scrotal hypoplasia. © 1993 Wiley‐Liss, Inc.
Cleft lip (± cleft palate) in Danish twins, 1970–1990
Authors: Christensen Kaare , Fogh‐Andersen Poul
Published: June 2005

A classical twin study is one of the best methods to address the open question of the role of genes and environment in the cause of cleft lip with or without cleft palate [CL(P)]. In addition, when twin concordance rates are combined with information about the risk for CL(P) to more remote relatives, they can help to establish the most likely mode of inheritance for CL(P).

The present study was based on three nation wide ascertainment sources of CL(P) in twins in Denmark during the period 1970‐1990. The Danish surgical files were found suitable for ascertaining twins with non‐syndromic CL(P) and a total of 39 pairs was identified through these files. In more than 70% of the cases, the zygosity assignment was based on unlike‐sex or an extensive panel of blood, serum, and enzyme types. More mono‐ and dizygotic twin CL(P) cases than expected were found, although the difference was not significant. The proband concordance rate for CL(P) was 60% in monozygotic twins and 10% in dizygotic twins; six cases were of unknown zygosity. This finding indicates that genetic factors play a major role in the cause of CL(P) but environmental and/or stochastic factors are probably acting too.

When the familial recurrence patterns analyzed by Mitchell and Risch 1992: Am J Hum Genet 51:323‐3321 are interpreted in light of these new estimates of monozygotic concordance, they provide further evidence for the finding that no single locus can account for more than a six‐fold increase in risk to first‐degree relatives. © 1993 Wiley‐Liss, Inc.
Association of familial duane anomaly and urogenital abnormalities with a bisatellited marker derived from chromosome 22
Authors: Cullen Paul , Rodgers Catherine S. , Callen David F. , Connolly Vincent M. , Eyre Helen , Fells Peter , Gordon Harold , Winter Robin M. , Thakker Rajesh V.
Published: June 2005

We report a spectrum of defects that were found in an 18‐year‐old girl who presented for investigation of primary amenorrhea. The patient was found to have Duane anomaly, left renal agenesis, absent uterus, bilateral sen‐sorineural deafness, and bilateral preauricular skin tags and sinuses. Investigation of her family showed that her brother also had Duane anomaly, right renal agenesis, sensorineural deafness, and preauricular skin tags. Cytogenetic analysis, including in situ hybridisation of peripheral blood lymphocytes, demonstrated a supernumerary bisatellited marker chromosome derived from the region of chromosome 22pter‐q11 in the affected individuals. Our findings indicate that a gene or genes located in the region of chromosome 22pter‐q11 may be associated with the Duane anomaly and the development of the urogenital tract. © 1993 Wiley‐Liss, Inc.
Uncombable hair, retinal pigmentary distrophy, dental anomalies, and brachydactyly: Report of a new patient with additional findings
Authors: Silengo M. , Lerone M. , Romeo G. , Calcagno E. , Martucciello G. , Jasonni V.
Published: June 2005

A new ecttodermal dysplasia syndrome was reported by Bork et al. in 1987 (Hautarzt 38:342–347). The syndrome consisted of hypotrichosis with the typical SEM (scanning electron microscopy) changes of uncombable hair, retinal pigmentary dystrophy, juvenile cataract, oligodontia, brachydactyly with brachymetacarpia; it was inherited as an autosomal dominant trait. We describe a sporadic case and add further chinical findings to expand the spectrum of this rare syndrome. © 1993 Wiley‐Liss, Inc.
Familial Brachmann‐de Lange syndrome: Further evidence for autosomal dominant inheritance and review of the literature
Authors: Feingold Murray , Lin Angela E.
Published: June 2005

We report on a mother and daughter with the Brachmann‐de Lange syndrome which supports the view that in some families this disorder is due to autosomal dominant inheritance. A review of the literature concerning autosomal and recessive inheritance of this syndrome is presented. © 1993 Wiley‐Liss, Inc.
Partial duplication of 3q (q25.1→q26.1) without the Brachmann‐de Lange phenotype
Authors: Lopez‐Rangel E. , Dill F. J. , Hrynchak M. A. , Van Allen M. I.
Published: June 2005

Partial duplications of chromosome 3 have previously been reported to have phenotypic characteristics similar to Brachmann‐de Lange syndrome (BDLS). We present the case of a 13‐Year‐old girl with an apparent duplication in the 3q25.1→q26.1 region but none of the manifestations commonly seen in BDLS. The chromosome 3 duplication was confirmed with a FISH painting probe of the involved region. These results suggest that the region critical for Brachmann‐de Lange syndrome is not within the duplicated region of 3q25.1→q26.1. © 1993 Wiley‐Liss, Inc.
Asymmetric and symmetric long bone bowing in two sibs: An apparently new bone dysplasia
Authors: Moore Laura A. , Moore Cynthia A. , Smith John A. , Weaver David D.
Published: June 2005

We describe 2 sibs, one with congenital asymmetric long bone bowing and one with congenital symmetric long bone bowing. Other bony abnormalities in these sibs include beaten metal appearance of the skull, dolichomacrocephaly, ocular hypertelorism, and anterior beaking and bone‐within‐bone appearance of vertebrae. A differential diagnosis including campomelic dysplasia, kyphomelic dysplasia, hypophosphatasia, Grant syndrome, and osteogenesis imperfecta, and a discussion of potential mechanisms of long bone bowing are presented. The condition that these sibs have shares some characteristics of the above bone disorders, but appears to be a separate entity which to our knowledge has not been described previously. © 1993 Wiley‐Liss, Inc.
Report on two patients with Costello syndrome and sialuria
Authors: Rocco Maja Di , Gatti Rosanna , Gandullia Paolo , Barabino Arrigo , Picco Paolo , Borrone Carla
Published: June 2005

We report on 2 unrelated patients with Costello syndrome. The first is a 5‐year‐old girl with “coarse” face, nasal papillomata, redundant skin of feet and hands, hyperextensible hand and finger joints, curly hair, feeding problems due to oral motor apraxia, growth and psychomotor retardation. The second is a 3‐year‐old boy with “coarse” face, loose skin on hands and feet, curly hair, oral motor apraxia, severe growth and psychomotor retardation. In both patients urine sialic acid levels were found to be repeatedly high. The meaning of this biochemical abnormality is discussed. © 1993 Wiley‐Liss, Inc.
Characterization of a small supernumerary ring X chromosome by fluorescence in situ hybridization
Authors: Duncan Alessandra M. V. , Macdonald Athen , Brown Carolyn J. , Wolff Daynna , Willard Huntington F. , Sutton Bernice
Published: June 2005

We report on a male with mild learning disabilities who has a supernumerary marker chromosome. The marker chromosome was defined by fluorescence in situ hybridization as a ring X chromosome with breakpoints in the juxacentromeric region. Replication studies suggest that the ring X is late‐replicating. However XIST, a gene in the X inactivation centre interval which is expressed exclusively from the inactive X chromosome, is not present on the marker, nor is it expressed in the patient's cells. These results are discussed with respect to karyotype‐phenotype correlations and X inactivation. © 1993 Wiley‐Liss, Inc.
Holoprosencephaly and primary craniosynostosis: The Genoa syndrome
Authors: Camera Gianni , Lituania Mario , Cohen M. Michael
Published: June 2005

We report on 2 sibs with holoprosencephaly of the semilobar type, unusual facial appearance not diagnostic of holoprosencephaly, and primary craniosynostosis involving the coronal and lambdoid sutures. The condition represents a newly recognized syndrome, possibly having autosomal recessive inheritance. © 1993 Wiley‐Liss, Inc.
Significance of mosaic isochromosome 20q on amniocentesis
Authors: Donnenfeld Alan E. , Kershner Melessa A.
Published: June 2005

We report on 2 fetuses with prenatally diagnosed mosaic isochromosome 20q in amniotic fluid. Neither had an identifiable cytogenetic abnormality after birth. One infant developed a benign intracranial dermoid cyst at age 8 months. The other was completely normal in all respects. We are aware of 13 fetuses with this prenatally diagnosed chromosome finding; all fetuses tested have had normal chromosomes on subsequent cytogenetic studies and all, except one, have been morphologically normal. Fetuses with mosaic isochromosome 20q identified on amniocentesis are are most likely to be phenotypically and cytogenetically normal after birth. © 1993 Wiley‐Liss, Inc.
Inverted duplication of chromosome 5p14p15.3 confirmed with in situ hybridization
Authors: Zenhger‐Hain Julie L. , van Dyke Daniel L. , Wiktor Anne , Walker Hugh , Feldman Gerald L.
Published: June 2005

Duplication of the short arm of chromosome 5 [dup(5)(p13.1p15.3)] has been associated with craniofacial malformations, cardiac defects, renal and intestinal malformations, limb abnormalities, and mental retaredation. We report a 2‐year‐old white girl with a denovo 46, XX, inv dup(5)(p14p15.3) chromosome constitution, who presented with motor and language delays, bilateral strabismus, small posteriorly angulated ears, a high‐arched palate, mild hypotonia, and an atrial septal defect. A CT scan of the head was normal. In situ hybridization with a cosmid probe specific for sub‐band 5p15.3 (Oncor, Inc., Gaithersburg, MD) was used to identify the origin and orientation of the extra material. The milder manifestations in our patient are consistent with the hypothesis that significant phenotypic effects are associated with duplication of material proximal to band 5p14. This study demonstrates the usefulness of in situ probes in identifying the origin and orientation of duplicated genetic material. © 1993 Wiley‐Liss, Inc.
Agenesis of the corpus callosum with mental retardation and osseous lesions
Authors: Kozlowski Dr K. , Ouvrier R. A.
Published: June 2005

We report on a patient with agenesis of corpus callosum, mental retardation, and unusual hitherto undescribed bone changes. The latter include multiple Wormian bones, thin ribs, short, straight, laterally tapering clavicles, small iliac bodies, high iliac angles, triangular areas of sclerosis in the iliac bones, minimal metaphyseal irregularity, striated trabecular pattern in some metaphyses, granular ossification pattern of the patellae, hypoplastic distal phalanges, minimal flatness of phalangeal epiphyses, and retarded bone age. This patient represents a new mental retardation syndrome with agenesis of corpus callosum and unusual bone changes. © 1993 Wiley‐Liss, Inc.
Do genes influence exposure to trauma? A twin study of combat
Authors: Lyons Michael J. , Goldberg Jack , Eisen Seth A. , True William , Tsuang Ming T. , Meyer Joanne M. , Henderson William G.
Published: June 2005

Data from 4,029 male‐male twin pairs who served in the United States military during the Vietnam era (1965–1975) were used to examine genetic and non‐genetic factors that influence wartime exposure to traumatic events. Specific events examined were volunteering for service in Vietnam, actual service in Southeast Asia, a composite index of 18 combat experiences, and information from military records about being awarded combat decorations. Correlations within monozygotic (MZ) and dizygotic (DZ) twin pairs for volunteering for service in Vietnam were 0.40 and 0.22, respectively. For actually serving in Southeast Asia, the MZ correlation was 0.41 and the DZ correlation was 0.24. Analysis of twin pairs in which both siblings served in Southeast Asia (n = 820) demonstrated a correlation for self‐reported combat experiences within MZ and DZ pairs of 0.53 and 0.30, respectively. Heritability estimates ranged from 35 to 47%. The family environment did not have a significant effect on any of the variables. Analyses of data from military records regarding being awarded a combat decoration provided very similar results to those found for self‐reported combat experiences. © 1993 Wiley‐Liss, Inc.
What is associated with the fragile X syndrome?
Authors: Fisch Gene S.
Published: June 2005

In addition to mental retardation (MR), fragile X [fra(X)] syndrome has been associated with a variety of other disorders. Despite earlier reports, it has been shown that MR fra(X) males are at no greater risk for autism than is any MR male. Therefore, studies in which fra(X) has been associated with behavioral, developmental, and psychopathological disabilities were examined to determine whether fra(X) individuals were at an increased risk for these dysfunctions as well. Psychiatric disorders among fra(X) individuals were found not to occur more frequently than in other individuals with cognitive deficits. It was also observed that hyperactivity and attention deficit disorder among MR fra(X) individuals do not occur more frequently than in other MR individuals. Pooled results from studies of cognitive profiles used to characterize fra(X) phenotypes also indicated that there are no consistent patterns in either males or females. Plausible explanations for a variable phenotype include allelic heterogeneity and pleitropy. © 1993 Wiley‐Liss, Inc.
Duchenne/becker muscular dystrophy carrier detection using quantitative PCR and fluorescence‐based strategies
Authors: Mansfield Elaine S. , Robertson James M. , Lebo Roger V. , Lucero Micheal Y. , Mayrand P. Eric , Rappaport Eric , Parrella Teresa , Sartore Maria , Surrey Saul , Fortina Paolo
Published: June 2005

Dystrophin gene deletions account for up to 68% of all Duchenne (DMD) and Becker (BMD) muscular dystrophy mutations. In affected males, these deletions can be detected easily using multiplex PCR tests which monitor for exon presence. In addition, quantitative dosage screening can discriminate female carriers. We previously analyzed multiplex PCR products by gel electrophoresis and quantitation of fluorescently labeled primers with the Gene Scanner™ in order to test carrier status. These multiplex PCR protocols detect DMD gene deletions adequately, but require up to 18 pairs of fluorochrome‐labeled primers. We previously described two alternative fluorescent labeling strategies, each with approximately 1,000‐fold greater sensitivity than ethidium bromide staining, which can be used to quantify the products of multiplex PCR. The first method uses the DNA intercalating thiazole orange dye TOTO‐1 to stain PCR products after 20 cycles. In the second method, fluorescein‐12,2′‐dUTP is incorporated into products during PCR as a fluorescent tag for subsequent quantitative dosage studies. Both methods label all multiplexed exons including the 506 bp exon 48 fragment that is difficult to detect and quantify by standard ethidium bromide staining. Using this approach, we determined DMD/BMD carrier status in 24 unrelated families using a fluorescent fragment analyzer. Analysis of fluorochrome‐labeled PCR products facilitates quantitative multiplex PCR for gene‐dosage analysis. © 1993 Wiley‐Liss, Inc.
Sclerocornea, hypertelorism, syndactyly, and ambiguous genitalia
Authors: Martínez‐Frías M. L. , Bermejo E. , Otero T. Sánchez , Urioste M. , Morena V. , Cruz E.
Published: June 2005

We present a child with an MCA pattern of sclerocornea, hypertelorism, pterygium colli, upper limb syndactyly, ambiguous genitalia, abnormal ears and nose, umbilical hernia, congenital heart disease, and normal chromosomes (46,XX). Although the defects observed in this case follow the diagnostic criteria for Fraser syndrome proposed by Thomas et al. [1986: Am J Med Genet 25:85–98], we think that this is a different entity. © 1994 Wiley‐Liss, Inc.
Gypsy phenylketonuria: A point mutation of the phenylalanine hydroxylase gene in Gypsy families from Slovakia
Authors: Kalanin Jan , Takarada Yutaka , Kagawa Shohei , Yamashita Keiko , Ohtsuka Norimitsu , Matsuoka Akira
Published: June 2005

A direct mutational analysis of the phenylala nine hydroxylase gene (PAH) in Gypsy families with phenylketonuria (PKU) has not yet been presented. However, they obviously represent a group at high risk for this inherited disease. We analyzed the PAH loci of 65 Gypsies originating from Eastern Slovakia by a combination of PCR amplification, direct sequencing and ASO hybridization. These studies uncovered 10 “classical PKU” patients to be homozygous for a R252W (CGG‐TGG) transition, and 29 heterozygous carriers of this mutation. Fifteen control Caucasoid PKU patients from the Czech and Slovak Republics were selected. In this group we detected R252W mutation in two subjects (6.67% of all mutant alleles). Both were compound heterozygous for two different mutations. Previous haplotype studies of Welsh Gypsies with PKU were uniformative in the determination of heterozygosity. ASO hybridization served us effectively for the consequent analyses in Gypsy PKU‐related families and to identify the carriers among the unrelated subjects. © 1994 Wiley‐Liss, Inc.
Short stature in a patient with Klinefelter syndrome and growth hormone deficiency
Authors: Rossodivita A. , Colabucci F.
Published: June 2005

We report on a child with Klinefelter syndrome and short stature due to idiopathic growth hormone deficiency (IGHD). His height was below the mid‐parental height, with a significant delay in bone age. Height velocity increased from 4.5 to 8.2 cm/year during 1 year of GH therapy and typical catch‐up growth was observed. No adverse reactions to the treatment were observed. We wish to emphasize the rare association between Klinefelter syndrome and IGHD and the apparent effectiveness and safety of recombinant somatotropin treatment in aneuploid patients. © 1994 Wiley‐Liss, Inc.
Deletion (11)(q14.1q21)
Authors: Stratton Robert F. , Lazarus Kenneth H. , Ritchie Elizabeth J. L. , Bell Ann Marie
Published: June 2005

We report on a 4‐year‐old girl with moderate developmental delay, horseshoe kidney, bilateral duplication of the ureters with right upper pole obstruction, hydronephrosis and nonfunction, and subsequent Wilms tumor of the right lower pole. She had an interstitial delection of the long arm of chromosome 11 involving the region 11(q14.1q21). © 1994 Wiley‐Liss, Inc.
Brachyolmia: An autosomal dominant form
Authors: Gardner Jessica , Beighton Peter
Published: June 2005

We have investigated a mother and son of South African Xhosa stock who presented with short‐trunk dwarfism and kyphoscoliosis. Radiographs show the marked platyspondyly and vertebral irregularity characteristic of brachyolmia. Our patients provide further evidence for the existence of an autosomal dominant form and supports the theory of heterogeneity in this rare group of genetic skeletal disorders. Molecular investigations in this South African family are currently underway but at present the basic defect of brachyolmia remains unknown. © 1994 Wiley‐Liss, Inc.
Delineatino of the da‐Silva syndrome
Authors: Naritomi Kenji , Tohma Takaya , Goya Yoshinobu , Shiroma Noboru , Hirayama Kiyotake
Published: June 2005

We present a 6‐month‐old boy with agenesis of the corpus callosum, hypertonicity, severe growth and psychomotor retardation, microcephaly, large prominent ears, and delayed bone age. Similarity of his manifestations to these in 3 sibs described by da‐Silva in 1988 suggests initial delineation of the da‐Silva syndrome. © 1994 Wiley‐Liss, Inc.
Stratton‐Parker syndrome: Confirmation of a new entity
Authors: Gabrielli Orazio , Carloni Ines , Catassi Carlo , Natalini Giuliana , Coppa Giovanni V. , Giorgi Pierluigi
Published: June 2005

Recently, Stratton and Parker [Am J Med Genet 32:169–173, 1989] reported on a child with a previously undescribed combination of growth hormone deficiency, wormian bones, dextrocardia, brachycamptodactyly, and other midline defects. We report on another patient with similar clinical signs. © 1994 Wiley‐Liss, Inc.
Relatively low proportion of dystrophin gene deletions in Israeli Duchenne and Becker muscular dystrophy patients
Authors: Shomrat Ruth , Gluck Eithan , Legum Cyril , Shiloh Yosef
Published: June 2005

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the X‐linked dystrophin gene. The most common mutations in western populations are deletions that are spread non‐randomly throughout the gene. Molecular analysis of the dystrophin gene structure by hybridization of the full length cDNA to Southern blots and by PCR in 62 unrelated Israeli male DMD/BMD patients showed deletions in 23 (37%). This proportion is significantly lower than that found in European and North American populations (55–65%). Seventy‐eight percent of the deletions were confined to exons 44–52, half of these to exons 44–45, and the remaining 22% to exons 1 and 19. There was no correlation between the size of the deletion and the severity of the disease. All the deletions causing frameshift resulted in the DMD phenotypes. © 1994 Wiley‐Liss, Inc.
Terminal deletion of the long arm of chromosome 2 in a premature infant with karyotype: 46,XY,del(2)(q37)
Authors: Wang Tung‐Ho , Johnston Kathreen , Hsieh Chih‐Lin , Dennery Phyllis A.
Published: June 2005

We present a premature newborn boy with multiple congenital anomalies, including craniofacial anomalies, syndactyly, cardiac defects, and a horseshoe kidney associated with terminal deletion of 2q. The infant's karyotype was 46,XY,del(2)(q37). Clinical, cytogenetic, and autopsy findings are presented in this report. Clinical manifestations in this infant are compared with those four other known patients with terminal deletion of chromosome 2. © 1994 Wiley‐Liss, Inc.
Linkage localization of the thoraco‐abdominal syndrome (TAS) gene to Xq25–26
Authors: Parvari R. , Weinstein Y. , Ehrlich S. , Steinitz M. , Carmi R.
Published: June 2005

The thoraco‐abdominal syndrome (TAS) presents a closure defect confined to the ventral midline, manifested as ventral hernia of various degrees in all affected individuals and antero‐lateral diaphragmatic defect manifested almost exclusively in affected males. The syndrome is inherited as an X‐linked dominant trait affecting blastogenesis (XLB mutation).

We studied 27 members of the TAS family for linkage on the X chromosome. The best lod score of 5.5 at θ 0.04 was found for the HPRT locus on Xq26.1. A multilocus lod score of 12.4 was observed when the linkage analysis utilized additional markers in Xq25–26. © 1994 Wiley‐Liss, Inc.
X‐linked laterality sequence in a family with carrier manifestations
Authors: Mikkilä S. P. , Janas M. , Karikoski R. , Tarkkila T. , Simola K. O. J.
Published: June 2005

X‐linked laterality sequence (XLLS) consists of situs inversus, complex cardiac defects, and alterations in the development of the spleen. We describe a family in which two male cousins had XLLS with caudal manifestations. In our family, the obligate carrier females had uterine septum and hypertelorism, which may be gene carrier manifestations. © 1994 Wiley‐Liss, Inc.
Identification of a small supernumerary ring chromosome 8 by fluorescent in situ hybridization in a child with developmental delay and minor anomalies
Authors: Melnyk A. R. , Dewald G.
Published: June 2005

We report a 15‐month‐old female with developmental delay, hypotonia, and minor anomalies whose karyotype is 47,XX, + r. Due to its small size, the origin of the ring chromosome was indeterminate by standard G‐banded karyotyping. Fluorescent in situ hybridization was performed, which indicated that the ring chromosome was derived from the pericentric region of chromosome 8. © 1994 Wiley‐Liss, Inc.
Prenatal diagnosis of unusual hemoglobinopathies
Authors: Kim Jong‐Hwa , Lebo Roger V. , Cai Shi‐Ping , Su Xia , Chung Jae‐Hyun , Mentzer William C. , Golbus Mitchell S.
Published: June 2005

While analyzing 280 hemoglobinopathy kindreds with prescribed molecular tests, 3 unusual mutations were observed that required additional characterization. In the first case, the hypervariable region flanking the α‐globin genes generated an intermediate length 8.2kb Ψζ‐globin gene fragment on a Southeast Asian chromosome with two deleted α‐globin genes. Rehybridization of the Southern blot with α‐globin probe distinguished the mutation unambiguously. In the second case, restriction enzyme analysis of a PCR amplified black β‐globin gene detected a novel β−83 point mutation adjacent to a promoter element. In the third case, which was uninformative with available allele specific oligonucleotides (ASOs), total genomic PCR amplification and sequencing identified a single basepair insertion in codon 36/37 of an Iranian β‐globin gene that shifted the reading frame and obliterated gene activity. Developing additional region‐specific ASOs will further diminish the number of cases that must be characterized by genomic PCR sequencing. © 1994 Wiley‐Liss, Inc.
Confirmation of proximal 1q duplication using fluorescence in situ hybridization
Authors: Chen Harold , Kusyk Christine J. , Tuck‐Muller Cathy M. , Martinez Jose E. , Dorand Rodney D. , Wertelecki Wladimir
Published: June 2005

We report on a boy with excessively wrinkled skin, mild micro/brachycephaly with mild hydrocephalus and slightly small temporal lobes, apparently low‐set ears, retro/micrognathia and cleft soft palate (Pierre‐Robin anomaly), patent ductus arteriosus and foramen ovale, pulmonary hypoplasia, eventration of the left hemidiaphragm, right cryptorchidism, a sacral dimple, flexion contractures of fingers and knees, and equinovarus deformities of both feet. The infant had a de novo dir dup(1)(pter→ q25::q12→qter). Partial duplications involving proximal 1q have rarely been reported. Furthermore, this is the first case of proximal duplication of chromosome 1q with unequivocal identification using fluorescence in situ hybridization (FISH) with a chromosome 1 painting probe. © 1994 Wiley‐Liss, Inc.
Anophthalmia, cleft lip/palate, facial anomalies, and CNS anomalies and hypothalamic disorder in a newborn: A midline developmental field defect
Authors: Leichtman Lawrence G. , Wood Brian , Rohn Reuben
Published: June 2005

We describe an infant with a unique pattern of midline defects, including anophthalmia, cleft lip and palate, macrocephaly, cutis aplasia, and micrognathia. CNS anomalies including massive hydrocephalus with destruction of most recognizable structures were observed. The infant also developed panhypopituitarism, diabetes insipidus, and a seizure disorder. We postulate that this patient could represent a more complex form of the Delleman syndrome or a new morphogenetic syndrome secondary to ventral induction with extension to the developmental fields of the first and second branchial arches. © 1994 Wiley‐Liss, Inc.
Hypoplasia of the cerebellar vermis and corpus callosum in thrombocytopenia with absent radius syndrome on MRI studies
Authors: MacDonald Madeleine R. , Schaefer G. Bradley , Olney Ann Haskins , Patton Donna F.
Published: June 2005

Thrombocytopenia with absent radius (TAR) syndrome is infrequently (7%) associated with mental retardation. In those cases, the mental deficiency is presumed to be a consequence of intracranial hemorrhage due to the thrombo‐cytopenia. We report on 2 infants with TAR syndrome. One had developmental delay with evidence of cerebral dysgenesis by magnetic resonance imaging (MRI). Such findings have not been noted in the literature, but may not have been investigated in most cases. The other infant with TAR syndrome, who has had normal psychomotor development, has a normal brain on MRI scan. Detailed neuroimaging studies, preferably MRI, should be considered in the evaluation of patients with TAR syndrome, especially when there are documented signs of developmental delay, with or without a history of intracranial hemorrhage. © 1994 Wiley‐Liss, Inc.
Confined placental chimerism: Prenatal and postnatal cytogenetic and molecular analysis, and pregnancy outcome
Authors: Falik‐Borenstein Tziporah C. , Korenberg Julie R. , Schreck Rhona R.
Published: June 2005

The presence of two cell lines in chorionic villi sampling (CVS) represents a significant complication in CVS analysis, interpretation, and counseling. We report on the cytogenetic and molecular analysis of a pregnancy that was conceived on clomiphen citrate. Two cell lines (46,XX and 47,XY, + 9) were discovered in CVS analysis done for maternal age; 94% of the cells in the culture were 46,XX and 6% were 47,XY, + 9 (the direct preparation was 46,XX). As neither line could have derived from the other, chimerism and not mosaicism was suspected, with the 47,XY, + 9 cells deriving from a co‐twin whose demise was the result of the autosomal trisomy. At a subsequent amniocentesis, only normal female cells were observed and a normal female infant was delivered at term. Cytogenetic analysis done on the infant's peripheral blood and on a sample of an umbilical vessel showed only 46,XX cells, while amnion and a fibrotic area of the placenta contained 2 cell lines, 46,XX and 47,XY, + 9.

Molecular analysis of 3 different tissues was done by the polymerase chain reaction (PCR) and Southern blotting, using Y specific primers and probes, respectively. The presence of Y specific DNA was detected in the placenta and amnion, but not in the umbilical blood vessel. These data excluded true chimerism in the fetal tissues at the level of about 1 in 105 cells and have defined for the first time probable confined placental chimerism (CPC), the result most likely of a “vanishing twin.” Whenever two cell lines are found in CVS, especially in the setting of pharmacologically stimulated ovulation, the possibility of CPC should be considered. The effects of CPC on placental function and fetal outcome merit further study. © 1994 Wiley‐Liss, Inc.
Cephalometric evidence for a dominantly inherited predisposition to cleft lip‐cleft palate in a single large kindred
Authors: Ward Richard E. , Bixler David , Jamison Paul L.
Published: June 2005

Several studies have demonstrated an association between facial shape in parents and the presence of oral clefts in their offspring. However, these observations have been of little practical value because it has been assumed that facial shape was just one predisposing component among many in a multifactorial model of inheritance. Cephalometric analysis of a large family with 5 generations of affected individuals suggests that facial shape can be used to identify presumed carriers of a major gene associated with an increased risk for oral clefts. Discriminant function analysis indicates that such at risk individuals can be recognized effectively through a combination of increased midfacial and nasal cavity widths, reduced facial height, and a flat facial profile. The ability to identify minimally affected gene carriers within families would provide critical information needed in the search for molecular markers that segregate with the genetic risk for clefting. © 1994 Wiley‐Liss, Inc.
Isochromosome 15q of maternal origin in two Prader‐Willi syndrome patients previously diagnosed erroneously as cytogenetic deletions
Authors: Saitoh Shinji , Mutirangura Apiwat , Kuwano Akira , Ledbetter David H. , Niikawa Norio
Published: June 2005

Since our previous report on two Prader‐Willi syndrome (PWS) patients with t(15q;15q) (Niikawa and Ishikiriyama; Hum Genet 69:22–27,1985) was erroneous, we report here new data and a corrected interpretation. Reexamination of the parental origin of their t(15q;15q) using polymorphic DNA markers that are mapped to various regions of 15q documented no molecular deletions at the 15q11‐q13 region in either patient. Both patients were homozygous at all loci examined and their haplotypes on 15q coincided with one of those in their respective mothers. These results indicate that the presumed t(15q;15q) in each patient was actually an isochromosome 15q producing maternal uniparental disomy, consistent with genomic imprinting at the PWS locus. © 1994 Wiley‐Liss, Inc.
Heteroduplex analysis of the dystrophin gene: Application to point mutation and carrier detection
Authors: Prior Thomas W. , Papp Audrey C. , Snyder Pamela J. , Sedra Mary S. , Western Lorraine M. , Bartolo Claire , Moxley Richard T. , Mendell Jerry R.
Published: June 2005

Approximately one‐third of the Duchenne muscular dystrophy patients have undefined mutations in the dystrophin gene. For carrier and prenatal studies in families without detectable mutations, the indirect restriction fragment length polymorphism linkage approach is used. Using a multiplex amplification and heteroduplex analysis of dystrophin exons, we identified nonsense mutations in two DMD patients. Although the nonsense mutations are predicted to severely truncate the dystrophin protein, both patients presented with mild clinical courses of the disease. As a result of identifying the mutation in the affected boys, direct carrier studies by heteroduplex analysis were extended to other relatives. We conclude that the technique is not only ideal for mutation detection but is also useful for diagnostic testing. © 1994 Wiley‐Liss, Inc.
Three new cases of the Schinzel‐Giedion syndrome and review of the literature
Authors: Labrune Philippe , Lyonnet Stanislas , Zupan Véronique , Imbert Marie‐Claire , Goutieres Françoise , Hubert Philippe , Le Merrer Martine
Published: June 2005

Three fetuses with normal chromosomes were found to have uni‐ or bilateral hydronephrosis during the third trimester of pregnancy. At birth, they presented with coarse face, hypertelorism, and a deep groove under the eyes. Fontanelles and sutures were wide open. Genital abnormalities were present in 2 cases. Skeletal radiographs showed delayed bone maturation, broad and dense ribs, and a wide synchondrosis between the exoccipital and supraoccipital bones. The combination of such findings suggested the diagnosis of Schinzel‐Giedion syndrome. Two patients died soon after birth, whereas the third one developed severe mental and motor retardation with seizures and spasticity, and died at 18 months.

Schinzel‐Giedion syndrome is rare and likely to be inherited as an autosomal recessive trait. So far, 13 well‐documented cases have been reported allowing major and minor traits of the syndrome to be distinguished. Since no genetic marker is available, the prenatal diagnosis of Schinzel‐Giedion syndrome relies on ultrasound examination, especially detection of renal abnormalities. © 1994 Wiley‐Liss, Inc.
Deletions of Xq and growth deficit: A review
Authors: Geerkens Claudia , Just Walter , Vogel Walther
Published: June 2005

A critical review of the literature disclosed 44 cases with a 46,X,Xq‐ karyotype without apparent mosaicism. Of these, 17 were of normal height (compared to the respective population), 11 had a height of over 1 SD below the mean, and 16 had a height of over 2 SD below the mean with breakpoints between Xq13 and Xq25. Since patients of normal height occurred with breakpoints as proximal as Xq13 we conclude that there is no major “growth gene” on Xq distal to q13. The most likely explanation for the variable phenotypic effect of Xq‐ is to assume that growth gene(s) in Xp or proximal Xq are inactivated on such a chromosome with some variability similar to the variable spreading of X inactivation seen in some X‐autosome translocations. © 1994 Wiley‐Liss, Inc.
Lower mesodermal defects: A common cause of fetal and early neonatal death
Authors: Pauli Richard M.
Published: June 2005

Among the first 1,130 referrals to the Wisconsin Stillbirth Service Program 17 infants have been recognized to share phenotypic characteristics involving the genital, urinary, lower gastrointestinal, and axial skeletal systems. The pattern of abnormalities identified appears to be limited to structures sharing a common embryologic origin. These features, for the most part, are shown to be non‐randomly associated. No clearly definable sub‐groups within this population are demonstrable. The pattern of abnormalities is defined to include abnormalities of the following structures as pathogenetically primary features: lumbosacral vertebrae, kidneys, ureters, uterus/fallopian tubes, vagina, bladder, urethra, adrenals, gonads, anorectum, external genitalia, and umbilical arteries. An embryologic mechanism is proposed which explains this non‐random association as arising secondary to disruption of structures derived from the lower portion of the primitive intra‐embryonic mesoderm. The Lower Mesodermal Defects Sequence appears to be a rather common (and under‐recognized) cause of stillbirth and immediate neonatal death. © 1994 Wiley‐Liss, Inc.
Duplication 20p identified via fluorescent in situ hybridization
Authors: LeChien Kay A. , McPherson Elizabeth , Estop Anna M.
Published: June 2005

A 3‐year‐old girl is reported with dup (20p) resulting from 3:1 segregation of a de novo t(20;21). The proposita presented with minor anomalies, developmental delay, a clinical phenotype suggestive of 20p trisomy, and a karyotype with a 21p+ and an additional small marker chromosome. Conventional cytogenetic techniques were not informative for the identification of the origin of the extra material of chromosome 21p nor for the marker chromosome. The 21p + and marker chromosomes were successfully characterized using fluorescent in situ hybridization (FISH). © 1994 Wiley‐Liss, Inc.
Growth hormone (GH), insulin‐like growth factors (IGFs), and IGF‐binding protein‐3 (IGFBP‐3) in a child with Proteus syndrome
Authors: Rudolph Günter , Blum Werner F. , Jenne Enno W. , Schöning Martin , Enders Herbert , Meitinger Thomas , Murken Jan D. , Kampik Anselm
Published: June 2005

Proteus syndrome is a congenital hamartomatous disorder characterized by partial overgrowth involving all germ layers. A somatic mutation model has been proposed since familial cases are extremely rare. We report on a 3‐year‐old girl with typical manifestations of Proteus syndrome, including local, asymmetric hypertrophy of various parts of the body. Total body length was reduced. Serum levels of IGF‐I and especially IGF‐II and their major growth hormone dependent binding protein (IGFBP‐3) were significantly reduced, although growth hormone secretion after a pharmacological stimulus was normal. In vitro studies of fibroblasts derived from hypertrophied tissue showed normal IGF‐I production and somewhat reduced IGF‐II and IGFBP‐3 production as compared to normal human skin fibroblasts.

Affinity cross‐linking experiments showed that fibroblasts of the affect tissue in Proteus syndrome produced an unusual pattern of IGF bindings proteins containing large amounts of an IGFBP with high affinity to IGF‐II. The data suggest that IGF production is generally disturbed in Proteus syndrome with imbalanced levels of specific IGFBP in affected tissue. © 1994 Wiley‐Liss, Inc.
Scalp‐ear‐nipple syndrome: Additional manifestations
Authors: Edwards Matthew J. , McDonald David , Moore Patrick , Rae John
Published: June 2005

Scalp‐ear‐nipple (SEN) syndrome is a rare, autosomal dominant condition that causes aplasia cutis congenita of the scalp, alteration of the shape of the external ear, and hypoplasia of the nipple. Women in a new family, the fifth to be described, had virtually complete aplasia of the breast and a small skin dimple without any pigmentation instead of a normal nipple, although other affected women had normal breast and nipple development. Dental changes included widely spaced or missing secondary teeth; the ears were cupped or folded and stood out from the head, axillary apocrine secretion and axillary hair growth were reduced; and finger nails were brittle. There was no generalized abnormality of sweating. Some patients had partial syndactyly of the 3rd and 4th fingers, and complete cutaneous syndactyly of the 2nd and 3rd toes. © 1994 Wiley‐Liss, Inc.
Recombinant chromosome 18 resulting from a maternal pericentric inversion
Authors: Ayukawa Hiroshi , Tsukahara Masato , Fukuda Masamichi , Kondoh Osamu
Published: June 2005

We report on a newborn girl with duplication of 18q12.2→18qter and deficiency of 18p11.2→18pter which resulted from meiotic recombination of the maternal pericentric inversion, inv(18) (p11,2q12.2). Her clinical manifestations were compatible with those of partial trisomy 18q syndrome. We review the previously reported 9 cases in 8 families of rec(18) resulting from recombination of a parental pericentric inversion. © 1994 Wiley‐Liss, Inc.
Developmental regulation of the expression of genes encoding proteins involved in cholesterol homeostasis
Authors: Ness Gene C.
Published: June 2005

The developmental patterns of expression of HMG‐CoA reductase, farnesyl pyrophosphate synthase, cholesterol 7α‐hydroxylase, and LDL receptor were investigated using Northern blotting analysis to quantitate mRNA levels. It was found that HMG‐CoA reductase and farnesyl pyrophosphate synthase mRNA levels in brain reached peaks at age 4 days which correlates with the time of peak enzyme activity and the onset of rapid brain growth and myelination. In liver, HMG‐CoA reductase and cholesterol 7α‐hydroxylase mRNA both rose dramatically at weaning. This is consistent with the concept that de novo synthesized cholesterol is the preferred substrate for cholesterol 7α‐hydroxylase and may also be involved in the induction of the enzyme. In testes, HMG‐CoA reductase activity was highest at age 21 days and then declined, while LDL receptor mRNA levels rose from age 31 to 120 days. These studies suggest a major role for de novo cholesterol synthesis in developing brain, liver, and testes. © 1994 Wiley‐Liss, Inc.
Smith‐Lemli‐Opitz syndrome: Biochemical before clinical diagnosis; early dietary management
Authors: Nwokoro Ngozi A. , Hyde Bruce , Mulvihill John J.
Published: June 2005

Pursuit of a possible metabolic basis for an unrecognized pattern of multiple congenital anomalies in a newborn girl led to the detection of a huge elevation of plasma 7‐dehy‐drocholesterol at age 8 months. The biochemical findings and the evolving clinical picture led to the diagnosis of Smith‐Lemli‐Opitz syndrome at age 11 months. High cholesterol diet may have improved the rate of developmental progress. © 1994 Wiley‐Liss, Inc.
Angelman syndrome due to paternal uniparental disomy of chromosome 15: A milder phenotype?
Authors: Bottani A. , Robinson W. P. , Delozier‐Blanchet C. D. , Engel E. , Morris M. A. , Schmitt B. , Thun‐Hohenstein L. , Schinzel A.
Published: June 2005

The Angelman syndrome (AS) is a neurological disorder characterized by severe mental retardation, absent speech, seizures, gait disturbances, and a typical age‐dependent facial phenotype. Most cases are due to an interstitial deletion on the maternally inherited chromosome 15, in the critical region q11–q13. Rare cases also result from paternal uniparental disomy of chromosome 15. In a group of 14 patients with sporadic AS diagnosed in Switzerland, we found 2 unrelated females with paternal isodisomy for the entire chromosome 15. Their phenotypes were milder than usually seen in this syndrome: one girl did not show the typical AS facial changes; both patients had late‐onset mild seizures; as they grew older, they had largely undisturbed gross motor functions, in particular no severe ataxia. Both girls were born to older fathers (45 and 43 years old, respectively). The apparent association of a relatively milder phenotype in AS with paternal uniparental disomy will have to be confirmed by detailed clinical descriptions of further patients. © 1994 Wiley‐Liss, Inc.
Mirror‐image dental fusion and discordance in monozygotic twins
Authors: Sperber G. H. , Machin G. A. , Bamforth F. J.
Published: June 2005

A pair of monozygotic twins had similar but not identical dental anomalies. One twin had fusion of deciduous mandibular lateral incisor and canine on the left, with normal dentition on the right; the co‐twin had right mandibular incisor/canine fusion, with aplasia of the lateral incisor on the left. These findings are discussed in the context of the related phenomena of situs inversus, mirror‐imaging in twins, and gradients of severity of anomalies in the four copies of the mandibular developmental dental field. © 1994 Wiley‐Liss, Inc.
Metacarpophalangeal pattern profile analysis in Sotos and Marfan syndrome
Authors: Dijkstra P. F. , Cole T. R. P. , Oorthuys J. W. E. , Venema H. W. , Oosting J. , Nocker R. E. T.
Published: June 2005

Patients with Sotos and Marfan syndrome have unusually long metacarpals and phalanges which may make the differential diagnosis difficult in younger children. Using Q‐scores, we compared metacarpophalangeal pattern profile (MCPP) analysis in these two syndromes and identified distinct and different pattern profiles. This illustrates that the MCPPs are specific in these syndromes, even at an early age, and not related solely to the unusually long metacarpals and phalanges. For this study we used data from 50 Sotos patients (34 from the United Kingdom and 16 from the Netherlands, with a total of 95 hand films) and 36 Marfan patients (from the Netherlands, with 98 hand films). Of all patients over age 3 years the bone length (including the epiphysis) was determined. The patients under 7½ years (29 Sotos and 12 Marfan) were also measured without inclusion of the epiphysis. The patients measured without epiphysis had a relative short metacarpal 1 (MC1) and long distal phalanx 1 (DPh1) in Sotos syndrome, and a relative long MC1 and short DPh1 in Marfan syndrome. Between age 3 and 7½ years more than 90% of the films could be classified correctly using these two variables. Of the roentgenograms measured with epiphyses, about 80% were classified correctly. © 1994 Wiley‐Liss, Inc.