bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial translocation resulting in Wolf‐Hirschhorn syndrome in two related unbalanced individuals: Clinical evaluation of a 39‐year‐old man with Wolf‐Hirschhorn syndrome
Authors: Wheeler Patricia G , Weaver David D. , Palmer Catherine G.
Published: June 2005

A chromosomal translocation between chromosomes 4 and 8 resulting in Wolf‐Hirschhorn syndrome in 2 individuals has been traced through 4 generations of a family. Ascertainment of the family was through a newborn infant with evident Wolf‐Hirschhorn syndrome who had an unbalanced chromosomal translocation [46,XY,−4,+der(4),t(4;8) (p15.32;p22)]. Discussion with the family documented a paternal great‐uncle who also had a similar phenotype and profound mental retardation. Subsequently this individual was found to have the same unbalanced chromosome constitution as the propositus. The 39‐year‐old great‐uncle is the oldest reported individual with the Wolf‐Hirschhorn syndrome. The importance of chromosome evaluation of older individuals with mental retardation syndromes is emphasized. © 1995 Wiley‐Liss, Inc.
Tooth agenesis in down syndrome
Authors: Russell Björn G. , Kjær Inger
Published: June 2005

We studied the frequency and pattern of tooth agenesis in a Danish population with Down syndrome, trisomy 21 (46 females and 54 males). The control group consisted of a normal Danish population (2424 females and 2431 males) [Rølling, 1980: Scand J Dent Res 88:365–369; Ravn and Nielsen, 1973: Tandlaægebladet 77:12–22]. We found that individuals with Down syndrome have an occurrence of agenesis that is some 10 times greater that in the general population with a higher frequency in males than in females. Agenesis occurred more frequently in the mandible than in the maxilla and most often on the left side. The highly significant differences were primarily found in the occurrence of agenesis of the mandibular central incisors, followed by the maxillary lateral incisors and second premolars and the mandibular second premolars. The main components in the pattern of agenesis observed in Down syndrome are supposed to be related to the peripheral nervous systern and abnormal cartilagenous tissue. The present study on Down syndrome suggests that the dentition, with its many different anomalies, from agenesis to malformation, can be used as an indicator in evaluating different aspects in the patheogenetic of aneuploidy conditions. © 1995 Wiley‐Liss, Inc.
Fetal akinesia and multiple perinatal fractures
Authors: Chen Harold , Blackburn Will R. , Wertelecki Wladimir
Published: June 2005

Two newborn infants with fetal akinesia sequence were noted to have multiple perinatal fractures of the long bones. The radiographic manifestations are characterized by gracile ribs, thin long bones, and multiple diaphyseal fractures. Consistent histopathologic changes of bone are irregular with focal areas of extreme diaphyseal thinning, thin and long marrow spicules, and with or without callous formation at fracture sites. Pathogenic mechanisms of bone fractures in fetal akinesia sequence and the differential diagnoses of congenital/perinatal bone fractures are discussed. © 1995 Wiley‐Liss, Inc.
Spondyloenchondromatosis: Syndromic identity and evolution of the phenotype
Authors: Zack P. , Beighton P.
Published: June 2005

We present case details and depict the phenotypic manifestations of a dwarfing skeletal dysplasia in an adolescent boy who was first seen in early childhood. His initial clinical and radiological findings resembled those of pseudoachondroplasia but these subsequently metamorphosed to an appearance which was diagnostic of spondyloenchondromatosis. It is uncertain whether this latter condition is a homogeneous entity or a group of heterogeneous disorders. Pedigree data were consistent with autosomal recessive inheritance. © 1995 Wiley‐Liss, Inc.
Multiple epiphyseal dysplasia with small head, congenital nystagmus, hypoplasia of corpus callosum, and leukonychia totalis: A variant of Lowry‐Wood syndrome?
Authors: Yamamoto Toshiyuki , Tohyama Jun , Koeda Tatsuya , Maegaki Yoshihiro , Takahashi Yoshika
Published: June 2005

We report on a boy with multiple epiphyseal dysplasia (MED), mild short stature, small head, mental retardation and congenital nystagmus associated with other visual problems. These manifestations were similar to those seen in Lowry‐Wood syndrome (LWS). He also had hypoplasia of the corpus callosum and leukonychia totalis, which were not described in the previous cases. © 1995 Wiley‐Liss, Inc.
Heterotaxia syndrome and autosomal dominant inheritance
Authors: Alonso Sandrine , Pierpont Mary Ella , Radtke Wolfgang , Martinez José , Chen Su‐Chiung , Grant James W. , Dähnert Ingo , Taviaux Sylvie , Romey Marie‐Catherine , Demaille Jacques , Bouvagnet Patrice
Published: June 2005

Previous familial cases of recurrent hetero‐taxia have suggested an autosomal recessive or exceptionally X‐linked or dominant inheritance. Here, we report six families including 18 affected members, consistent with autosomal dominant inheritance. Among these, four families have more than one case of heterotaxia. The other two families have one member with heterotaxia and at least one other affected member with an “isolated” heart malformation, which could be considered as a mild form of heterotaxia. In five families, the disorder is transmitted through two or three generations. In one family, the patients are of the same generation but are linked to each other by obligate carriers. We suggest a rule to classify these families with heart malformations, according to the etiologic factor involved (rule of precocity). This rule might be useful to other disruptions of morphogenetic processes. © 1995 Wiley‐Liss, Inc.
Acampomelic campomelic syndrome and sex reversal associated with de novo t(12;17) translocation
Authors: Ninomiya Shinsuke , Narahara Kouji , Tsuji Kazushiro , Yokoyama Yuji , Ito Satoko , Seino Yoshiki
Published: June 2005

The association of rare chromosomal rearrangements involving a specific 17q breakpoint with campomelic syndrome (CMPS) and or sex reversal (SR) has led to an assignment of the CMPS1 SRA1 locus to 17q24.3→q25.1. We describe a patient with multiple anomalies and SR, who had a de novo t(12;17) translocation. The phenotype was consistent with that of CMPS except for the lack of lower limb bowing and talipes equinovarus. Chromosome painting indicated that the breakpoints appeared to have occurred at 12q21.32 and 17q24.3 or q25.1. This study suggests that acampomelic CMPD with SR represents a variant of the CMPS1/SRA1 locus disorder. We emphasize the likelihood that CMPS may be a contiguous gene syndrome. © 1995 Wiley‐Liss, Inc.
Down syndrome consequent to a cryptic maternal 12p;21q chromosome translocation
Authors: Scott Jennifer A. , Wenger Sharon L. , Steele Mark W. , Chakravarti Aravinda
Published: June 2005

A 9‐year‐old, mildly mentally retarded girl presented with phenotypic manifestations of Down syndrome. G‐banded chromosomal analyses of peripheral blood lymphocytes from the patient and her parents, and skin fibroblasts from the patient, did not detect any abnormality. Molecular analysis of 15 highly polymorphic chromosome 21 dinu‐cleotide repeat markers demonstrated a partial duplication of the Down syndrome critical region (D21S55, subband 21q22.2) of maternal origin in the patient. The segmen‐tal trisomy was confirmed by FISH analysis using the cosmid probe D21S55. Further analysis demonstrated that the trisomy was due to segregation of an apparently balanced cryptic translocation from the mother. The patient's karyotype is 46,XX,‐12, tder(12)t(12;21)(p13.1;q22.2)mat. © 1995 Wiley‐Liss, Inc.
Major gene is responsible for anencephaly among Iranian Jews
Authors: Zlotogora Joël
Published: June 2005

Anencephaly is relatively frequent in Jews originating from Iran, in particular when its incidence is compared to that of open spina bifida in the same population (12 cases of anencephaly out of 14 cases of neural tube defects). The high incidence of this disorder in Iranian Jews, a relatively isolated community with a very high rate of consanguinity, suggests that anencephaly is caused by a major recessive gene. This possibility is supported by the sex ratio among these patients, which was significantly different from that observed for patients with anencephaly in other populations. © 1995 Wiley‐Liss, Inc.
Classical Noonan syndrome is not associated with deletions of 22q11
Authors: Robin Nathaniel H. , Sellinger Beatrice , McDonald‐McGinn Donna , Zackai Elaine H. , Emanuel Beverly S. , Driscoll Deborah A.
Published: June 2005

Deletions of 22qll cause DiGeorge sequence (DGS), velo‐cardio‐facial syndrome (VCFS), conotruncal anomaly face syndrome, and some isolated conotruncal heart anomalies. Demonstration of a 22qll deletion in a patient with manifestations of DGS and Noonan syndrome (NS) has raised the question of whether NS is another of the chromosome 22 microdeletion syndromes. This prompted us to evaluate a cohort of patients with NS for evidence of 22qll deletions. Five of 6 NS propositi studied in our laboratory with marker N25 (D22S75) did not have a 22qll deletion. A 2‐month‐old infant with several findings suggestive of NS did have a 22qll deletion, suggesting that a small number of 22qll deletion propositi may present with a NS‐like picture. However, most cases of NS must have another cause. © 1995 Wiley‐Liss, Inc.
Molecular cytogenetic study of supernumerary marker chromosomes in an unselected group children
Authors: Gravholt Claus Højbjerg , Friedrich Ursula
Published: June 2005

We report on an unselected group of 24 children with small supernumerary marker i chromosomes, found in a large sample of 34,910 consecutive newborns karyotyped at I birth. Sixteen of these were available for re‐examination. With the use of in situ hybridization with a‐satellite centromere probes and satellite III, ribosomal and (3‐satellite DNA probes, we have characterized these markers. In 14 of the 16 cases we have been able to determine the chromosomal origin of the marker. Twelve of the markers are derived from the acrocentric chromosomes. Of these 12 markers, 4 are derived from chromosome 14, 4 from chromosome 22, 3 from I chromosome 15 and one is from either chromosome 13 or 21. Ten of these markers were j initially ascertained with the satellite III DNA probe, taking advantage of the fact 1 that satellite III DNA is found in the cen‐I tromeric region of the following chromo‐J somes: 1, 5, 9, 13, 14, 15, 16, 20, 21, 22, and Y. I Two markers were derived from chromo‐) somes 4 and 8. The origin of the last 2 mark‐i ers could not be determined with the techniques employed. Only one of these children is psychometrically retarded and has a pe culiar appearance. Unfortunately we were; not able to determine the origin of the I marker in her case. All other children developed normally. © 1995 Wiley‐Liss, Inc.
Choledochal cyst associated with rare hand malformation
Authors: Dudin Anwar , Abdelshafi Mustafa , Rambaud‐Cousson Annie
Published: June 2005

We report on an 8‐year‐old boy with choledochal cyst associated with most unusual hand malformation. Review of the literature and possible etiopathogenesis are discussed. © 1995 Wiley‐Liss, Inc.
Craniofacial and dental characteristics of Silver‐Russell syndrome
Authors: Kotilainen Johanna , Hölttä Päivi , Mikkonen Tapio , Arte Sirpa , Sipilä Ilkka , Pirinen Sinikka
Published: June 2005

We found significant differences in a craniometric, cephalometric, and dental study of 19 Silver‐Russell syndrome patients (13 without growth hormone treatment) with appropriate controls. Although head circumference was normal for age, head length was increased, while cranial and facial widths and facial heights were reduced. Posterior facial height, posterior cranial base length, cranial base height, and mandibular body size were significantly smaller than in healthy children of the same height. Articulatory speech disorders were common. Enamel defects pointed to an early prenatal insult. Delayed dental age and small mandibular and cranial base dimensions support the possibility of physiological growth hormone deficiency in many Silver‐Russell syndrome children; however, facial soft tissue structures were strikingly different from those observed in classical growth hormone deficiency. © 1995 Wiley‐Liss, Inc.
Prenatal diagnosis and fetopathological findings in five fetuses with trisomy 9
Authors: Chitayat David , Hodgkinson Kathy , Luke Anthony , Winsor Elizabeth , Rose Toby , Kalousek Dagmar
Published: June 2005

Five male fetuses with trisomy 9 are discussed. Three were detected prenatally and terminated, 1 aborted spontaneously, and the fifth delivered prematurely and died soon after. Multiple congenital abnormalities characteristic of trisomy 9 were detected in all 5 cases and are compared to those of previous reports. © Wiley‐Liss, Inc.
Unusual case of Smith‐Lemli‐Opitz syndrome “type II”
Authors: Seller Mary J. , Russell J. , Tint G. S.
Published: June 2005

We describe a fetus with abnormalities suggestive, but not typical, of severve Smith‐Lemli‐Opitz syndrome (SLO). Biochemical studies demonstrated that there was a defect of cholesterol biosynthesis similar to that recently discovered in children with SLO. The findings in this fetus extend even further the wide spectrum of abnormalities of the SLO phenotype, andemphasize that a genetic pathological examination and biochemical studies should always be undertaken on atypical cases, especially fetuses. © Wiley‐Liss, Inc.
Smith‐Lemli‐Opitz syndrome: Prenatal diagnosis by quantification of cholesterol precursors in amniotic fluid
Authors: Rossiter Judith Pratt , Hofman Karen J. , Kelley Richard I.
Published: June 2005

Until recently, the diagnosis of Smith‐Lemli‐Opitz syndrome (SLOS), an autosomal recessive malformation/mental retardation syndrome, was made on the basis of clinical criteria alone. As a result, prenatal diagnosis has been possible only if sonography disclosed distinct fetal malformations in a subsequent pregnancy. However, the recent description of increased levels of 7‐dehydrocholesterol (cholesta‐5,7‐dien‐3β‐ol) in patients with SLOS, most likely caused by a deficiency of 3β‐hydroxysteroid‐δ7‐reductase, has provided an apparently reliable biochemical marker for diagnosis of SLOS. To determine if this abnormality of sterol metabolism has utility for prenatal diagnosis of SLOS, we measured the levels of neutral sterols in stored amniotic fluid samples from two SLOS pregnancies. In both cases, the diagnosis of SLOS was made in the neonatal period by clinical criteria and the finding of markedly increased levels of 7‐dehydrocholesterol in plasma. Quantitative analysis by gas chromatography of sterols extracted from the amniotic fluid of both pregnancies revealed similar, markedly increased levels of 7‐dehydrocholesterol and its precursor, lathosterol (cholest‐7‐en‐3β‐ol), both of which were undetectable in reference amniotic fluids. These findings suggest that abnormalities of cholesterol biosynthesis in SLOS may be sufficiently expressed in fetal life to permit prenatal diagnosis of this disorder by measurement of 7‐dehydrocholesterol in amniotic fluid. © Wiley‐Liss, Inc.
De novo tandem duplication of chromosome segment 22q11‐q12: Clinical, cytogenetic, and molecular characterization
Authors: Lindsay Elizabeth A. , Shaffer Lisa G. , Carrozzo Romeo , Greenberg Frank , Baldini Antonio
Published: June 2005

We report on a case of duplication of the segment 22q11–q12 due to a de novo duplication. Molecular cytogenetics studies demonstrated this to be a tandem duplication, flanked proximally by the marker D22Z4, a centromeric alpha satellite DNA repeat, and distally by D22S260, an anonymous DNA marker proximal to the Ewing sarcoma breakpoint. The segment includes the regions responsible for the “cat‐eye,” Di George, and velo‐cardio‐facial syndromes and extends distal to the breakpoint cluster region (BCR). The clinical picture is dominated by the cardiac defects and includes findings reminiscent of “cat‐eye” syndrome. These findings reinforce the hypothesis that the proximal 22q region contains dosagesensitive genes involved in development. © Wiley‐Liss, Inc.
Histopathology of fetal diastrophic dysplasia
Authors: Qureshi F. , Jacques S. M. , Johnson S. F. , Johnson M. P. , Hume R. F. , Evans M. I. , Yang S. S.
Published: June 2005

We report on three cases of diastrophic dysplasia in second trimester fetuses and discuss the differential diagnosis and clinical, radiologic, and histopathologic findings. Manifestations of typical diastrophic dysplasia in infants and older patients include abnormal pinnae, scoliosis, and joint contractures; these were absent in the fetuses, in keeping with the tendency for the clinical and radiologic aspects of this disease to become more severe with age. The histopathologic characteristics of the cartilage appear to be similar in the fetus and older patient, and therefore may be useful in differentiating diastrophic dysplasia from other osteochondrodysplasias in the second trimester. © Wiley‐Liss, Inc.
Further study of genetic interactions: Loss of short arm material in patients with ring chromosome 4 changes developmental pattern of del(4)(q33)
Authors: Lurie Iosif W.
Published: June 2005

Segment 4q33 is not considered a probable location of a gene related with limb deficiency by Roberts and Tabin [Am J Hum Genet 55:1–6, 1994]; however, the occurrence of ectrodactyly or its equivalents in at least 9 published cases of monosomy 4q33 suggests probable location of one of these genes in that region. Ulnar ray defects and/or ectrodactyly were the prevailing forms. An additional loss of the tip of 4p in patients with ring chromosome 4 leads to a change of limb deficiency type: 8 of 9 patients with r(4) and limb deficiency had radial ray defects. Therefore, interactions between a proposed ½ dose “ectrodactyly” gene on 4q33 and some ½ dosage genes on distal 4p (or disturbed cellular homeostasis due to a ring chromosome 4) can change the developmental pattern of limb deficiency. Possible mechanisms and significance of the Phenomenon are discussed. © Wiley‐Liss, Inc.
Evidence for Ritscher‐Schinzel syndrome in Canadian native Indians
Authors: Marles Sandra L. , Chodirker Bernard N. , Greenberg Cheryl R. , Chudley Albert E.
Published: June 2005

We report on 8 (3 male, 5 female) native Canadian children with distinctive facial appearance and variable combinations of ocular colobomas, hypertelorism, macrocephaly, hand anomalies, congenital heart defects, structural CNS posterior fossa malformations, and mental retardation. These 8 children belong to 7 families; 3 of the families are related. The parents and other sibs are clinically unaffected. We think these manifestations provide evidence for Ritscher‐Schinzel syndrome in native Canadian children, and we have confirmed that ocular colobomas are a common occurrence in this disorder. © 1995 Wiley‐Liss, Inc.
Prenatal diagnosis of retinal nonattachment in the Walker‐Warburg syndrome
Authors: Chitayat David , Toi Ants , Babul Riyana , Levin Alex , Michaud Jacques , Summers Ann , Rutka James , Blaser Susan , Becker Laurence E.
Published: June 2005

We report on the prenatal ultrasonographic diagnosis of Walker‐Warburg syndrome based on cerebral and ocular findings. The ultrasound study done at 37 weeks gestation documented hydrocephalus and retinal nonattachment consistent with this syndrome. The ability to detect retinal nonattachment prenatally may have implications for the prenatal diagnosis of other conditions which have early retinal nonattachment as one of their findings. However, it is uncertain how early in pregnancy this defect can be detected. © 1995 Wiley‐Liss, Inc.
Primary midline developmental field. I. Clinical and epidemiological characteristics
Authors: Martínez‐Frías María‐Luisa
Published: June 2005

Opitz [BD: OAS XXIX(1): 3‐37, 1993] has postulated that during early blastogenesis the entire embryo represents a single morphogenetic unit, the primary field. During this period, beginning gastrulation, the most important events are the formation of the midline and the mesoderm. Consequently, one could expect that dysmorphogenetic reactions of the primary field are likely to disturb more than one of the essential events of blastogenesis, such as fusion, lateralization, decussation, segmentation, morphogenetic movements, asymmetry formation, etc.

I have used the 20,891 liveborn malformed infants identified by the Spanish Collaborative Study of Congenital Malformations (ECEMC) to analyze the concept of the primary field defect (DFD). The malformed children were separated into 4,679 children with only midline defects, 1,592 children with midline plus other non‐midline anomalies, and 14,620 babies without midline defects. Sex, twinning, neonatal death, parental consanguinity, and other malformed first degree relatives in the family were analyzed in each group. Different defects were selected as indicators of specific morphogenetic events of blastogenesis. Cardiac and neural tube defect were selected as indicators of fusion anomalies; agenesis/hypoplasia of the corpus callosum were included as example of decussation defect; cyclopia as representation of the alteration of lateralization; vertebral defects as indicators of anomalies of segmentation; intestinal malrotation and omphalocele as representatives of the alteration of the morphogenetic movement; and, finally, infants with asplenia, polysplenia, dextrocardias, transposition of great vessels, visceral transposition, and situs inversus totalis were grouped to allow an analysis of alteration of the normal body asymmetry.

The results of this analysis demonstrate, from an epidemiological standpoint, that the infants with midline anomalies have alteration of the normal body asymmetry more frequently than infants without midline defects. Children with midline anomalies have more severe malformations with high lethality, associated with twinning, without sex differences in occurrence, and with low recurrence risk, than do infants without midline defects, as was suggested by Opitz [BD: OAS XXIX(1): 3–37, 1993]. © 1995 Wiley‐Liss, Inc.
Replication banding and molecular studies of a mosaic, unbalanced dic(X;15)(xpter→xq26.1::15p11→15qter)
Authors: Scheuerle Angela , Zenger‐Hain Julie L. , Van Dyke Daniel L. , Ledbetter David H. , Greenberg Frank , Shaffer Lisa G.
Published: June 2005

We present a patient with a chromosomal mosaicism involving the X chromosome. One cell line is 45,X and the other has a de novo paternally derived dicentric X;15 translocation. Her karyotype is therefore 45,X/45,X,dic(X;15)(Xpter→Xq26.1: : 15p11→15 qter) based on G‐banding. The presence of 2 centromeres on the derivative X was confirmed by fluorescence in situ hybridization (FISH) and a deletion of Xq26.1→qter was confirmed by polymerase chain reaction (PCR) using DXS52 and DXYS154. Replication banding studies indicate that the derivative X is late replicating. Based on these studies, it is unclear whether inactivation has spread to proximal 15q. The patient has a unique phenotype distinct from Ullrich‐Turner or Prader‐Willi syndromes, but includes ataxia and language delay which are commonly seen in Angelman syndrome. These findings are contrary to those anticipated since deficiency of paternal genes at 15q12 typically leads to Prader‐Willi syndrome. Molecular analysis of PCR‐based polymorphisms of chromosome 15 and X indicates that uniparental disomy is not present for the X chromosome or chromosome 15 in either cell line. It is hypothesized that her phenotype results from the interaction of the 2 abnormal genotypes. Each abnormality may be diluted by the mosaicism and, in the derivative X line, by the possible variation among cells of inactivation spreading to chromosome 15. © 1995 Wiley‐Liss, Inc.
High resolution genetic map of the adenomatous polyposis coli gene (APC) region
Authors: Olschwang Sylviane , Laurent‐Puig Pierre , Melot Thomas , Thuille Bénédicte , Thomas Gilles
Published: June 2005

Familial adenomatous polyposis coli (APC) is a dominantly inherited colorectal cancer susceptibility disease caused by mutation in a gene called APC and located on chromosome 5q21. Presymptomatic diagnosis of this condition is recommended because it enables restriction of the efficient but demanding prevention program to those relatives that are genetically affected. The large size of the APC gene makes the direct search for the causal alteration difficult to implement in routine diagnostic laboratories. Because APC appears to be genetically homogeneous with alteration in a single locus causing the disease, cosegregation analysis may represent an alternative efficient method for presymptomatic diagnosis. However, the reliability of the risk estimation by linkage analysis in APC families is hampered by the lack of a short range genetic map of the APC locus. A combined approach including genotyping of 65 APC families, analysis of the CEPH database, and complementary typing of both APC and CEPH families has made it possible to derive the following genetic map: Centromere‐[D5S82‐D5S49]‐0.02‐D5S122‐0.01‐D5S136‐0.01‐D5S135‐0.02‐[APC‐D5S346‐MCC]‐0.04‐[D5S81‐D5S64]‐Telomere. This order, which differs from previously proposed genetic maps, is fully compatible with recent physical mapping data. These data should contribute to increase the reliability of the presymptomatic test for APC. © 1995 Wiley‐Liss, Inc.
Mixed sclerosing bone dysplasia, small stature, seizure disorder, and mental retardation: A syndrome?
Authors: Jurenka Stanislava B. , Van Allen Margot I.
Published: June 2005

We present a 40‐year‐old man with mental retardation, short stature, minor anomalies, and seizures, who was found to have osteopoikilosis with melorheostosis (mixed sclerosing bone dysplasia, MSBD). Cytogenetic findings of a low level trisomy 8 mosaicism were not confirmed by fluorescence in situ hybridization (FISH) of fibroblast cells. To our knowledge, the association of MSBD and mental retardation has not been previously reported. © 1995 Wiley‐Liss, Inc.
Lipoma of corpus callosum associated with dysraphic lesions and trisomy 13
Authors: Wainwright Helen , Bowen Robert , Radcliffe Marlon
Published: June 2005

We report on a further case of corpus callosal lipoma and frontal cranial defects. Most cases in the literature of corpus callosal lipoma in association with “dysraphic” lesions have been frontal in location. Malformation of the corpus callosum is said to be associated with 50% of these lipomas. Trisomy 13 was confirmed by the 13q14 cosmid probe on paraffin‐embedded liver tissue. © 1995 Wiley‐Liss, Inc.
Further contribution to the description of phenotypes associated with partial 4q duplication
Authors: Zollino M. , Zampino G. , Torrioli G. , Pomponi M. G. , Neri G.
Published: June 2005

We report on a 15‐year‐old girl with a previously undescribed de novo duplication of segment 4q13.1→q22.2. The origin of the extrachromosomal material on 4q was unequivocally established by fluorescent in situ hybridization with a chromosome 4 painting probe. Clinical manifestations included moderate mental retardation, destructive behavior, and minor physical anomalies. An analysis of the literature on partial 4q trisomy led us to identify a region comprising bands 4q22‐q23, which may be involved in the development of the acrorenal field. © 1995 Wiley‐Liss, Inc.
Topographic variabilities of immunoreactivity to subunit c of mitochondrial ATP synthase and lectin binding in late infantile neuronal ceroid‐lipofuscinosis
Authors: Kida Elzbieta , Wisniewski Krystyna E. , Connell Fred
Published: June 2005

A subset of lipophilic neurons in the brain tissue of late infantile neuronal ceroid lipofuscinosis (LINCL) cases shows in addition to finely granular storage lipopigment, larger spheroidal lysosomal inclusions, so called protein‐type myoclonus bodies. Their incidence, significance, and biochemical composition have not been determined. To further characterize this type of lysosomal storage material, immunocytochemistry to subunit c of mitochondrial ATP synthase at the light and electron microscopy level, electron microscopy, and lectin histochemistry were applied. The majority of spheroidal inclusions were nonreactive to subunit c, the main protein component of the storage material in LINCL. These inclusions also showed no binding sites for the eight lectins examined, although six of the lectins used labeled finely granular storage material. According to electron and immunoelectron microscopy, spheroidal inclusions were composed of more homogeneous and more densely arranged material than typical curvilinear profiles, with shorter membranous profiles and sometimes filamentous structures. The dissimilarities disclosed between finely granular lipopigment with curvilinear profiles and spheroidal inclusions in LINCL brain tissue suggest that either protein(s) other than subunit c are present in spheroidal inclusions, or subunit c in these sites undergoes conformational or proteolytic changes. These changes require further biochemical evaluations. © 1995 Wiley‐Liss, Inc.
Significance of lipopigments with fingerprint profiles in eccrine sweat gland epithelial cells
Authors: Goebel Hans Hilmar , Warlo Irene , Klockgether Thomas , Harzer Klaus
Published: June 2005

Lipopigments with fingerprint profiles in eccrine sweat gland epithelial cells are regular findings in childhood NCL. They have also been described in adult NCL (ANCL) a few times, but not consistently. However, they have been considered nonspecific when not matched by similar abnormal profiles in noneccrine sweat gland epithelial cells. These conflicting reports may pose a diagnostic dilemma as outlined in the following 2 examples. Patient 1 is a 20‐year‐old man who developed severe tetraparesis and dementia over 2 years. Electroencephalogram was abnormal with epileptiform discharges. The patient died at age 21 years without autopsy; no other relatives are known to have a similar disease. Patient 2, a 49‐year‐old woman, developed ataxia and gait abnormalities when 44 years old, and, later, psychosis and dementia. The patient is still alive; no other family members are similarly affected. Both patients lacked evidence of a retinopathy clinically, funduscopically, and by electroretinography. Both patients showed lipopigments within secretory eccrine sweat gland epithelial cells which harbored unequivocal fingerprint profiles, but not within noneccrine sweat gland cells. Regular lipofuscin was observed in other cells, including skeletal muscle fibers of patient 2. © 1995 Wiley‐Liss, Inc.
Immunelectronmicroscopic characterization of T4 and T8 lymphocytes and natural killer cells in neuronal ceroid‐lipofuscinosis
Authors: Kieseier Bernd C. , Goebel Hans Hilmar
Published: June 2005

CD4+, CD8+, and CD56+ cells were isolated with the immunomagnetic separation technique from peripheral blood mononuclear cells (PBMC) of 3 patients with neuronal ceroid‐lipofuscinosis: one patient each with infantile (INCL), late infantile (LINCL), and juvenile (JNCL) neuronal ceroid‐lipofuscinoses, all studied by light (LM) and electron (EM) microscopy. To compare the pathology of these cells with affected cells in other types of lysosomal diseases, the separation was also performed with PBMC of 1 patient with mucolipidosis (ML) type II, 2 patients with mucopolysaccharidosis (MPS) type I, and 4 patients with MPS type III. Diseasespecific lysosomal inclusions were identified in CD4+, CD8+, and CD56+ cells. Subclass‐specific storage products could not be found. T4 and T8 lymphocytes showed nearly the same ratio of affected to nonaffected cells.

These results suggest that lysosomal storage can be found in most of the lymphocyte subclasses in these forms of neuronal ceroid‐lipofuscinoses and other lysosomal diseases. © 1995 Wiley‐Liss, Inc.
Late‐infantile Batten disease: Purification of the subunit c of the mitochondrial ATP synthase from storage material
Authors: Hagopian Kevork , Lake Brian D. , Winchester Bryan G. , Clark John B.
Published: June 2005

The accumulation of subunit c of the mitochondrial ATP synthase in late‐infantile neuronal lipofuscinosis (LINCL) and juvenile neuronal lipofuscinosis (JNCL) is well documented. The purification of the subunit from diverse sources has been reported previously, although not from the brain of Batten disease patients. This proteolipid has now been purified from late‐infantile Batten disease brain. The procedures used were an original combination of the conventional solubilisation, differential centrifugation, organic solvent extractions, preparative gel electrophoresis, and FPLC. Gel filtration of the purified protein indicated molecular mass equal to or greater than 2 × 106 Da; however, electrophoresis of this pure protein suggested a molecular mass of approximately 3,500 Da, which is a characteristic of subunit c. The pure protein may be solubilised in aqueous buffer containing <1% lithium dodecyl sulphate (LDS). The protein binds dicyclohexylcarbodiimide (DCCD) and shows immunoreactivity to antibodies raised against ovine storage bodies. © 1995 Wiley‐Liss, Inc.
Variant proteins in ovine ceroid‐lipofuscinosis
Authors: Moroni‐Rawson Pisana , Palmer David N. , Jolly Robert D. , Jordan T. William
Published: June 2005

Two‐dimensional polyacrylamide gel electrophoresis has been used to search for diseaserelated protein variation in South Hampshire sheep with ovine ceroid‐lipofuscinosis. Several hundred proteins in homogenates and subcellular fractions from livers have been examined, using isoelectric focusing as the first dimension separation, and SDS PAGE in the second dimension. Under these circumstances it was not possible to detect subunit c of the Fo region of ATP synthase, as this protein did not enter the isoelectric focusing gels. However, our studies emphasize the selective nature of misprocessing of subunit c, as we have not been able to detect any other consistent variation between affected and control animals for over 200 mitochondrial fraction proteins. Comparison of the presence or absence, and abundance, of proteins from isolated storage bodies with their counterparts in subcellular fractions from normal liver indicated that storage bodies contained a small subset of mitochondrial proteins, in addition to subunit c, with possible minor contributions from lysosomal, microsomal, and soluble proteins. Analysis of extramitochondrial proteins showed greater than 10–20‐fold accumulation of ferritin light chains in microsomes, and partial loss of a putatively lysosomal protein, in ovine ceroid‐lipofuscinosis. In addition, senescence marker protein was more abundant in the cytoslic fraction of controls, compared with affected individuals. We are currently investigating the basis and significance of these differences. © 1995 Wiley‐Liss, Inc.
Abnormal acid phosphatases in neuronal ceroid‐lipofuscinoses
Authors: Khan K. M. Faisal , Brooks Susan Sklower , Pullarkat Raju K.
Published: June 2005

Acid phosphatases in brain and cultured lymphoblasts from patients affected with neuronal ceroid‐lipofuscinoses (NCL) were studied by starch gel electrophoresis. After electrophoresis the gel was incubated with 4‐methyl umbelliferyl phosphate at pH 4.5 and the fluorescent reaction product was visualized under ultraviolet light. Control brain showed a single band with mobility of about 1 cm while NCL patients showed two additional fast moving bands. In the lateinfantile, and in the adult form (Kufs disease), the middle band was prominent while the fast moving band was predominant in juvenile NCL. In long‐term lymphoblasts, controls showed a single band of acid phosphatase activity while both juvenile and late‐infantile NCL showed two additional fast moving bands. Obligate heterozygotes showed reduced levels of the fast moving bands. Fluorometric assay of acid phosphatase using 4‐methylumbelliferyl phosphate as substrate showed a 2‐fold increase in activity in the patients. The increased acid phosphatase activity is completely inhibited by tartrate. Lymphocyte hexosamnidase activities were unchanged in NCL patients lymphoblasts. Studies on brains of NCL patients and on cultured lymphoblasts from families with late‐infantile and juvenile form of NCL showed that abnormal acid phosphatase is characteristic of NCL © 1995 Wiley‐Liss, Inc.
Mitochondrial damage results in a reversible increase in lysosomal storage material in lymphoblasts from patients with juvenile neuronal ceroid‐lipofuscinosis (Batten disease)
Authors: Boriack Richard L. , Cortinas Elma , Bennett Michael J.
Published: June 2005

We have previously demonstrated reduced phospholipid fatty acid content in blood cells and cultured skin fibroblasts from patients with JNCL. This has led to an experimental treatment regimen consisting of dietary supplementation with polyun‐saturated fatty acids (PUFAs).

In order to study the effects of PUFA supplementation in vitro, we have developed a laboratory model based upon cultured lymphoblast cell lines. We have transformed lymphocytes from four JNCL patients in whom disease linkage to chromosome 16 was informative. Cells from patients and controls were cultured with and without antibiotic (50 μg/ml gentamycin) and with and without PUFA supplementation.

None of the control cells demonstrated significant storage under any of the above conditions. In gentamycin treated cells, we observed that many of the mitochondria were damaged. In addition, cells from patients incubated with gentamycin demonstrated large accumulations of autofluorescent storage material. Disease cells grown in the presence of antibiotic and PUFAs did not demonstrate a significant accumulation of storage material; this suggests a direct relationship between mitochondrial damage and storage of autofluorescent material. Moreover, it appears that this storage (but not mitochondrial damage) is reversed by the addition of PUFAs. © 1995 Wiley‐Liss, Inc.
Erythrocyte membrane reacylation in juvenile neuronal ceroid‐lipofuscinosis: Measurement of membrane‐bound carnitine palmitoyl transferase, acyl‐CoA synthetase, and lysophospholipid: Acyl‐CoA acyltransferase activities
Authors: Bennett Michael J. , Boriack Richard L.
Published: June 2005

In order to study the biochemical mechanisms responsible for the membrane fatty acid deficiency in juvenile neuronal ceroidlipofuscinosis, we have analyzed the reacylation pathway in isolated erythrocyte membranes in 5 patients. We studied membrane carnitine palmitoyl transferase, and developed a combined assay to study acyl‐CoA synthetase and lysophospholipid acyl‐CoA acyltransferase activities. There were no significant differences between control and patient membranes, suggesting that abnormalities in these 3 putative candidate enzymes are not responsible for the disease.
Application of chromosome 16 markers in the differential diagnosis of neuronal ceroid‐lipofuscinosis
Authors: Taschner Peter E. M. , de Vos Nanneke , Catsman‐Berrevoets Coriene E. , van Duinen Sjoerd G. , Lindhout Dick , Breuning Martijn H.
Published: June 2005

Accurate diagnosis of neuronal ceroid lipofuscinosis (NCL) is important for a correct prognosis of the disease and for genetic counseling. Up to now, no direct diagnostic test has been available for NCL. The clinical diagnosis is made on the basis of symptoms, neurophysiological, neuroradiological, and specific lipopigment pattern data. Recent advances in the genetics of NCL have enabled us to use polymorphic DNA markers linked to the CLN1 and CLN3 loci as a tool in the differential diagnosis of NCL. We have applied genetic analysis with polymorphic DNA markers flanking the CLN3 gene on chromosome 16 to two consanguineous families in which NCL occurs. In the first family, which is of Turkish extraction, two patients suffering from a protracted form of juvenile NCL previously had been diagnosed with juvenile NCL. Haplotypes from this family indicate that the patients and their healthy sibling are haplo‐identical, suggesting that this protracted form of juvenile NCL is not linked to the CLN3 locus. In the second family, which is of Moroccan origin, one patient suffers from the early juvenile variant of NCL (Lake‐Cavanagh). In this family, the patient and one of the healthy siblings have identical haplotypes, excluding linkage of early juvenile NCL to the CLN3 locus on 16p12.1‐11.2. Therefore, these cases from different populations demonstrate that haplotype analysis can be used as an additional method to exclude the diagnosis of juvenile NCL. © 1995 Wiley‐Liss, Inc.
Linkage analysis of late‐infantile neuronal ceroid‐lipofuscinosis
Authors: Sharp Julie , Savukoski Minna , Wheeler Ruth B. , Harris Juliette , Järvelä Irma , Peltonen Leena , Gardiner Mark , Williams Ruth
Published: June 2005

The neuronal ceroid‐lipofuscinoses (NCL) are a group of neurodegenerative disorders with an autosomal‐recessive pattern of inheritance. There are 3 main categories of childhood NCL, namely, infantile, late‐infantile, and juvenile NCL. These can be distinguished on the basis of age of onset, clinical course, and histopathology. A number of variant forms of NCL have also been described, and these show symptoms intermediary between the main classical forms. The genes for both the infantile and juvenile forms of NCL have previously been mapped to chromosome areas 1p32 and 16p12, respectively. The gene for late‐infantile NCL (LINCL), CLN2, has been excluded from both these loci, but its location is as yet unknown. Recently, CLN5, the gene for the Finnish variant form of LINCL, was mapped to 13q21.1–32. Using the 3 microsatellite markers which were most tightly linked to CLN5, we have excluded CLN2 from this region using a subset of 17 families. Thus, CLN2 represents a fourth distinct genetic locus involved in the pathogenesis of NCL. © 1995 Wiley‐Liss, Inc.
Renal anomalies in Marden‐Walker syndrome: A clue for prenatal diagnosis
Authors: Ben‐Neriah Ziva , Yagel Simcha , Ariel Ilana
Published: June 2005

Marden‐Walker syndrome is an autosomal‐recessive disorder characterized by psy‐chomotor retardation, blepharophimosis, joint contractures, arachnodactyly, failure to thrive, and, infrequently, renal anomalies. We report on the prenatal diagnosis of Marden‐Walker syndrome in a fetus which had had a previously affected sib with this syndrome. The ultrasonic findings indicative of the diagnosis in this fetus were in‐trauterine growth retardation and renal cystic disease. We emphasize the importance of renal anomalies which, when present in combination with other ultrasound evidence of this syndrome, should be used as a clue for the diagnosis of Marden‐Walker syndrome. © 1995 Wiley‐Liss, Inc.
Velo‐cardio‐facial syndrome: Frequency and extent of 22q1l deletions
Authors: Lindsay Elizabeth A. , Goldberg Rosalie , Jurecic Vesna , Morrow Bernice , Carlson Christine , Kucherlapati Raju S. , Shprintzen Robert J. , Baldini Antonio
Published: June 2005

Velo‐cardio‐facial. (VCFS) or Shprintzen syndrome is associated with deletions in a region of chromosome 22q11.2 also deleted in DiGeorge anomaly and some forms of congenital heart disease. Due to the variability of phonotype, the evaluation of the incidence of deletions has been hampered by uncertainty of diagnosis. In this study, 54 patients were diagnosed with VCFS by a single group of clinicians using homogeneous clinical criteria independent of the deletion status. Cell lines of these patients were established and the deletion status evaluated for three loci within the commonly deleted region at 22q11.2 using fluorescence in situ hybridization (FISH). In 81% of the patients all three loci were hemizygous. In one patient we observed a smaller interstitial deletion than that defined by the three loci. The phenotype of this patient was not different from that observed in patients with larger deletions. © 1995 Wiley‐Liss, Inc.
Interstitial duplication 19p
Authors: Stratton Robert F. , Dupont Barbara R. , Olsen Anne S. , Fertitta Anne , Hoyer Mark , Moore Charleen M.
Published: June 2005

We report on a 9‐month‐old girl with an interstitial duplication of 19p, developmental delay, and multiple anomalies including bifrontal prominence, obtuse frontonasal angle, short columella, additional midline philtral pillar, midline ridge on the tongue, vertical midline ridge at the mental symphysis, and a complex congenital heart defect including severe branch pulmonary artery stenosis, secundum atrial septal defect (ASD), and several ventricular septal defects (VSDs). Use of fluorescent in situ hybridization (FISH) with chromosome 19‐specific probes showed a direct duplication of bands 19p13.13 and 19p13.2. © 1995 Wiley‐Liss, Inc.
Patient with craniosynostosis and marfanoid phenotype (Shprintzen‐goldberg syndrome) and cloverleaf skull
Authors: Saal Howard M. , Bulas Dorothy I. , Allen Jill Fonda , Vezina L. Gilbert , Walton Dawn , Rosenbaum Kenneth N.
Published: June 2005

Marfanoid phenotype with craniosynostosis (Shprintzen‐Goldberg syndrome) is a rare disorder previously described in only 5 patients. We report on the sixth known patient with this condition. The findings which distinguish our patient from others reported previously are that she was ascertained prenatally as having a cloverleaf skull; this is the first female patient described with this condition. Postnatally, she presented with arachnodactyly, camptodactyly and cloverleaf skull. Imaging studies of the brain documented microcephaly with malformed brain, hydrocephaly, and hypoplasia of the corpus callosum. She also had choanal atresia and stenosis, a clinical finding previously reported only once, in this disorder. © 1995 Wiley‐Liss, Inc.
Interstitial deletions of the short arm of chromosome 4 in patients with a similar combination of multiple minor anomalies and mental retardation
Authors: White Donna M. , Pillers De‐Ann M. , Reiss Jacob A. , Brown Michael G. , Magenis R. Ellen
Published: June 2005

Interstitial deletions of chromosome 4 have been described rarely and have had variable presentations. We describe the phenotypic characteristics associated with interstitial deletion of the p14–16 region of chromosome 4 in 7 patients with multiple minor anomalies in common, and with mental retardation. A review of published cases of interstitial deletions of the short arm of chromosome 4 is provided. These deletions present a distinct phenotype which is different from that of Wolf‐Hirschhorn syndrome. © 1995 Wiley‐Liss, Inc.
Autosomal dominant osteosclerosis type stanescu: The third family
Authors: Horovitz Dafne Dain Gandelman , Neto João Goncalves Barbosa , Boy Raquel , Vargas Fernando Regla , Llerena Juan Clinton , de Almeida José Carlos Cabral
Published: June 2005

We describe a family with Stanescu osteosclerosis. The propositus and his mother were short and had cortical sclerosis of the long bones, deficient facial sinus development, cranial bone malformations, and normal intelligence. To the best of our knowledge, only two such families have been described previously. The autosomal dominant pattern of inheritance of this skeletal dysplasia is reinforced, as there are many other reportedly affected relatives, including the maternal grandfather, uncles, and aunts of the propositus. The findings of wormian bones and calcification of the falx, not previously described, may be added to the phenotype. © 1995 Wiley‐Liss, Inc.
CHARGE association in a child with de novo inverted duplication (14)(q22 → q24.3)
Authors: North Kathryn N. , Wu Bai Lin , Cao Benning N. , Whiteman David A. H. , Korf Bruce R.
Published: June 2005

We report on a 4‐1/2 year old girl with apparent CHARGE association who had a de novo inverted duplication (14)(q22 → 24.3), iris colobomas, ventricular septal defect, soft tissue choanal atresia, intellectual impairment, growth retardation, sensorineural deafness, apparently low set ears, and upslanting palpebral fissures. Family history was unremarkable and parental chromosomes were normal. Similarities between this and previously reported cases of 14q duplication suggest that a locus for a gene or genes causing some of the anomalies of CHARGE association may reside in the region 14q22 to 24.3. © 1995 Wiley‐Liss, Inc.