bluuebunny/crossref_metadata_2025 huggingface dataset:
RFLP analysis for diagnosis of haemophilia A in the German Democratic Republic
Authors: Herrmann F. H. , Wehnert M. , Wulff K.
Published: July 2010

The frequencies of Bcl I, Hind III and Xba I intragenic polymorphic sites in the population of the GDR were found to be 0.68, 0.38 and 0.48, respectively. No differences in composition and frequencies were detectable at DXS 52 locus in comparison with other Caucasian populations. A strong linkage disequilibrium between the intragenic Bcl I and Hind III sites could be confirmed. The observed heterozygosity for the flanking marker DXS 52 in combination with intragenic Bcl I and Xba I polymorphisms was 0.97.

Using these three RFLPs, 122 females at risk in 41 independent haemophilia A families were investigated; 86 of them could be identified and 27 excluded as carriers; 9 females could not be classified. So far, four prenatal diagnoses in the first trimester of gestation have been performed by RFLP analysis.
Maternal serum markers in screening for Down syndrome
Authors: Nørgaard‐Pedersen Bent , Larsen Severin Olesen , Arends Jørgen , Svenstrup Birgit , Tabor Ann
Published: July 2010

The addition of two new markers in maternal serum, estriol and HCG, to those already known, namely the level of maternal serum alfa‐fetoprotein and maternal age, considerably improves the expected results of a screening strategy for Down syndrome. The detection rate is slightly increased from 53.0% to 57.6%, but, more importantly, the false‐positive rate decreases from 9.4% to 7.3%. It is our belief that, at least in women aged less than 35 years, a screening strategy based on a combination of maternal age and biochemical markers should be incorporated into antenatal care. For older women, the results of such a maternal serum test may refine counseling for genetic amniocentesis, as a much more explicit risk calculation can be performed than that based on age alone.
Lack of specificity of DA/DAPI fluorescence
Authors: Lin M. S. , Huynh K. H. , Fujimoto A. , Wilson M. G.
Published: July 2010

Cytogenetic studies showed 47,XY, + mar in a developmentally retarded child with some features of Prader‐Willi syndrome, and 46,XX in his mother. The marker chromosome showed a single subterminal primary constriction, bisatellites, and two C‐bands. DA/DAPI staining showed two intense bands in the marker chromosome, which most likely was derived from chromosome 15.

Intense DA/DAPI fluorescence was also found in one chromosome 13 in the child, and one 13 and one 10 in his mother. The present results confirm the reports of DA/ DAPI heteromorphism in acrocentric chromosomes other than the 15, and demonstrate a pericentric DA/DAPI heteromorphism in chromosome 10.
Defective oxidation of pristanic acid by fibroblasts from patients with disorders in propionic acid metabolism
Authors: Poulos A. , Johnson D. , Singh H.
Published: July 2010

The a‐methyl fatty acid, pristanic acid (2, 6, 10, 14 tetramethylpentadecanoic acid) is oxidised rapidly by normal skin fibroblasts in culture to CO2 and to water‐soluble metabolites. The latter are secreted into the culture medium. Fibroblasts from patients with propionyl CoA carboxylase, and to a lesser extent from patients with methylmalonyl CoA mutase defects, show reductions in the amount of CO2 released, although the production of water‐soluble metabolites is not affected. Our data indicate that propionic acid is produced from pristanic acid, and ultimately from its immediate precursor phytanic acid. As phytanic and pristanic acids are significant components of diets rich in ruminant fats, it is likely that they may contribute to the accumulation of propionate and its metabolites in disorders of propionate metabolism.
Mental retardation, craniofacial dysmorphism, hypogonadism, diabetes mellitus and epilepsy in four siblings. A “new” mental retardation syndrome
Authors: Fryns J. P. , Vogels A. , van den Berghe H.
Published: July 2010

In this report we describe a distinct and apparently new mental retardation syndrome in four siblings: three brothers and one sister. They present slight to moderate mental retardation associated with a peculiar craniofacial dysmorphism (4/4), hypergonadotrophic hypogonadism (4/4), eunuchoid habitus (4/4), diabetes mellitus (4/4) and epilepsy (3/4).
Deletion of chromosome 1p: a short review
Authors: Howard P. J. , Porteus M.
Published: July 2010

A further patient with a deletion of lp is described, bringing the number of reported cases to 13. The cytogenetic derivation of the deletions and the clinical phenotype are reviewed. The range of breakpoints and small number of cases result in no clearly defined phenotype. Facial dysmorphism, clinodactyly of the fifth finger, mental retardation and heart defects are, however, most frequently described, with a high‐arched palate, in particular, seen in deletions distal to P34.
Trisomy 17p due to a t(8; 17) (p23; p11.2)pat translocation. Case report and review of the literature
Authors: Schrander‐Stumpel C. , Schrander J. , Fryns J. P. , Hamers G.
Published: July 2010

We describe a female newborn girl with partial trisomy 17p, which was not detected at the initial cytogenetic investigation, but which later proved to be an unbalanced product of a paternal translocation t(8; 17)(p23;pl 1.2). Comparison with the three previously reported patients suggests a clinically distinct “trisomy 17p syndrome”, i.e. pre‐ and postnatal growth retardation, microcephaly, antimongoloid slanting of palpebral fissures, hypertelorism, long philtrum with thin upper lip, micrognathia and high‐arched palate. Two of the four patients had a heart defect, and psychomotor developmental delay was evident in all four cases. In the present patient, the chromosomal anomaly was only detected after the finding of the autosomal reciprocal translocation in the father. The importance of cytogenetic investigations in parents of a MCA/MR child with apparently normal chromosomes is emphasized.
Proximal 15q variant as possible pitfall in the cytogenetic diagnosis of Prader‐Willi syndrome
Authors: Hoo Joe‐Jie , Chao Margaret C. , Samuel Iris P. , Morgan Andrew M.
Published: July 2010

A patient with Prader‐Willi syndrome showed an elongated proximal 15q, and thus was initially considered to be negative for a proximal 15q deletion. However, repeated high resolution chromosome study demonstrating the DNA‐replication banding patterns revealed an obvious deletion/deficiency of the 15q12 equivalent band on that elongated chromosome 15. This deletion was further verified by comparison with the parental chromosomes 15 and the deleted chromosome 15 was of paternal origin. The elongation was due to a long variant of 15q11.2 band, which has previously been shown to be polymorphic/variable. This variable proximal 15q site could potentially mask a deletion if it is too long, or mimic a deletion if it is too short. The use of the DNA‐replication banding technique instead of the more widely used trypsin banding technique could alleviate this possible pitfall.
A case of 46,XX,r(X) (p1q1) diagnosed byin situhybridization
Authors: Koch J. , Kølvraa S. , Hobolt N. , Petersen G. B. , Willard H. F. , Waye J. S. , Gregersen N. , Bolund L.
Published: July 2010

A small marker chromosome was identified as an X‐derived ring chromosome byin situhybridization with a biotinylated X‐chromosome specifica‐satellite DNA probe. This procedure clearly determined the chromosomal origin of the marker chromosome, which had been impossible to define by conventional cytogenetic techniques including high resolution banding.
A linkage study of malignant hyperthermia (MH)
Authors: Bender K. , Senff H. , Wienker T. F. , Spiess‐Kiefer C. , Lehmann‐Horn F.
Published: July 2010

Five German families segregating for malignant hyperthermia (MH) were tested for linkage relationships using 35 serological and biochemical markers. Slightly positive lod scores were obtained with MNS, EsD, C3 and P. The relation with the C3 locus on chromosome 19p13.3–13.2 (ž=0.72, θ= 0.11) is of some interest, since genetic linkage of MH with several polymorphic DNA markers from the 19q12–13.2 region has been reported (McCarthy et al. 1989).
High resolution banding of an unusual reciprocal translocation in recurrent abortions
Authors: Kroisel P. M. , Rosenkranz W.
Published: July 2010

Reciprocal translocations involving two chromosomes frequently cause abortion of unbalanced offspring. In many cases, however, meiosis leads to a cytogenetically normal or balanced gamete with normal embryonal development. In a couple investigated because of recurrent reproductive loss, the husband had a recìprocal exchange of parts of the long arms of chromosomes 9 and 10 in the form of inverted insertions. Due to difficulties in obtaining regular homologous pairing during zygotene, this anomaly might not be compatible with cytogenetically normal or balanced offspring. The diagnosis of this translocation was possible using a previously published alkaline Giemsa G‐banding technique.
Phenotype of two males with abnormal Y chromosomes
Authors: Mićić M. , Mićić S. , Babić M. , Diklić V.
Published: July 2010

Two infertile males with sex chromosomal abnormalities and mosaic karyotype, 45,X/ 46,X,dic(Yq) and 45,X/46,X,ring(Y), had considerably changed physical findings, including tooth sizes and craniofacial dimensions. Spermatogenesis was preserved with abnormal meiotic chromosomal behaviour. Mosaic karyotype and structurally changed Y chromosome in both cases had an influence on physical parameters. Testes were normally developed and spermatogenesis was preserved but depressed in later stages.
Marfan syndrome: a diagnostic dilemma
Authors: Viuoen Denis , Beighton Peter
Published: July 2010

During a 17‐year period (1971–1988), the Marfan syndrome was diagnosed in 66 patients seen through the Department of Human Genetics, Medical School, University of Cape Town. Following reappraisal and application of the Pyeritz criteria, this diagnosis was confirmed in 33. Of the others, 17 with tall stature and a Marfanoid habitus had insufficient additional manifestations for firm diagnosis and were eliminated from the series. Sixteen had Marfanoid habitus, tall stature, arachnodactyly and other abnormalities which might have indicated the presence of a different syndrome. The difficulty in making a clinical diagnosis of the Marfan syndrome is stressed and emphasizes the need for a biomolecular marker.
Haplotype analysis for CF‐linked DNA polymorphisms in Switzerland
Authors: Liechti‐Gallati S. , Niederer B. U. , Schneider V. , Mächler M. , Alkan M. , Malik N. , Braga S. , Moser H.
Published: July 2010

A total of 295 patients, parents and unaffected sibs from 106 CF‐families in central and northeastern Switzerland were investigated with probes 7C22(D7S16), metH, metD, pKM19, pXV‐2c and pJ3.11(D7S8) for eight DNA polymorphisms (RFLP's). Linkage disequilibrium to the CF locus and haplotype frequencies were compared to those in other populations. They are comparable to other Caucasian populations and, for pKM 19 and pXV‐2c, very close to the findings in Italy. The prevalence of certain haplotypes among the CF and the normal allele‐bearing chromosomes indicate that the majority of the CF cases are probably the result of one ancient mutation in a common ancestor, but that there may be allelic heterogeneity accounting for an important proportion of patients, that may differ between countries or regions. Informative family constellations for the different polymorphisms in Switzerland and strategies for carrier detection and prenatal diagnosis are discussed. Haplotype analyses for each country and its ethnic subgroups are recommended.
Rate of recombination of chromosomes 21 in parents of children with Down syndrome
Authors: Hamers A. J. H. , Meyer H. , Jongbloed R. J. E. , van der Hulst R. R. W. J. , Geraedts J. P. M.
Published: July 2010

To test the hypothesis of reduced chiasma frequency causing nondisjunction during meiosis, we examined 34 Down syndrome patients and their parents. Chromosomal polymorphisms and RFLP markers were used to trace the parental origin as well as the frequency of recombination of chromosomes 21. In all but one case, the parental origin and the meiotic stage of nondisjunction could be established by either technique. In 11 cases recombination could be deduced to have taken place during meiosis in the parent who contributed the extra chromosome 21. Because of the underestimation which is inherent in the methods used, these results do not seem to support the chiasma theory.
Restriction site polymorphism at the LPA (Lp(a) apoliprotein; apoliprotein(a)) locus
Authors: Berg Kåre , Kondo Ikuko , Drayna Dennis , Lawn Richard
Published: July 2010

A restriction site polymorphism in the Lp(a) apoliprotein gene (the LPA gene) is reported. The basis for the polymorphism is presence or absence of an MspI restriction site that appears to be 3‘ to the last kringle IV structure of the gene. The “1” gene (presence of the restriction site) has a frequency of 0.316 and the “2” gene (absence of the restriction site) has a frequency of 0.684. Both members of each of 67 monozygotic (MZ) twin pairs had the same genotype and there was Mendelian segregation of the DNA variants in 40 families with a total of 75 children. There was a lower proportion of people with genotype 1–1 in the top quartile than in the 3 bottom quartiles of the population distribution of Lp(a) lipoprotein levels but the difference did not reach statistical significance.
Ratio of fetal to maternal DNA is less than 1 in 5000 at different gestational ages in maternal blood
Authors: Gänshirt‐Ahlert D. , Pohlschmidt M. , Gal A. , Miny P. , Horst J. , Holzgreve W.
Published: July 2010

Using Southern hybridization with the DNA probe pY3.4, we were not able to detect fetal DNA in blood of 36 pregnant women carrying male fetuses. Gestational ages ranged from 8–40 weeks of pregnancy. Using the same DNA probe, we were able to detect the male‐specific signal in experimental dilution series down to 1/5000 on autoradiograms. We conclude that the ratio of fetal DNA in maternal circulation, in contrast to previous estimations, must be lower than 1/5000.
Rhizomelic chondrodysplasia punctata and survival beyond one year: a review of the literature and five case reports
Authors: Wardinsky T. D. , Pagon R. A. , Powell B. R. , McGillivray B. , Stephan M. , Zonana J. , Moser A.
Published: July 2010

Rhizomelic chondrodysplasia punctata (RCDP), a peroxisomal disorder, is considered to be a lethal neonatal autosomal recessive chondrodysplasia. We report five patients, three of whom survived beyond 1 year, and we summarize the findings in 21 patients from a literature review who survived beyond 1 year. In those patients that survive, there is a high association of spasticity, psychomotor retardation, growth failure, seizures, thermoregulatory instability, feeding difficulty, and recurrent otitis media and pneumonia. Three of our five patients had no radiographic evidence of vertebral body clefts, a finding which has previously been considered invariable in RCDP. Three of our patients had distinctive facies that differ from the classic Conradi‐Hunermann facies.
Megalocornea, macrocephaly, mental and motor retardation (MMMM)
Authors: Frydman M. , Berkenstadt M. , Raas‐Rothschild A. , Goodman R. M.
Published: July 2010

Two patients with macrocephaly, mild mental retardation and megalocornea are reported. Hypotonia, poor coordination and swallowing difficulties were present. One patient was obese and the other had scoliosis. Both had large fleshy ears and long fingers. The spectrum of the mental retardation megalocornea syndrome is not fully defined. These two patients resemble a previously reported case, and although there are distinct differences from patients with familial or sporadic Neuhauser syndrome, these cases may represent clinical variability of that syndrome.
Sporadic late onset ornithine transcarbamylase deficiency in a boy with somatic mosaicism for an intragenic deletion
Authors: Legius E. , Baten E. , Stul M. , Marynen P. , Cassiman J.‐J.
Published: July 2010

Somatic mosaicism for a deletion in the ornithine transcarbamylase gene is described in a boy with sporadic late onset ornithine transcarbamylase deficiency. These findings are discussed in relation to the clinical picture of the patient and in relation to genetic counseling.
Familial caudal dysgenesis: evidence for a major dominant gene
Authors: Rudd Noreen L. , Klimek Mary L.
Published: July 2010

Four sibs with varying degrees of caudal dysgenesis are described. Case 1 showed aberrant umbilical cord vasculature with a single umbilical artery near the placental insertion. Cases 2 and 3 showed full sirenomelia, one with a complex congenital heart defect. Case 4 had an imperforate anus and an excessively long umbilical cord. The father's half‐sib had an imperforate anus, rectovaginal fistula and genitourinary anomalies. A dominant gene with reduced penetrance is likely.
Hemophilia B: diagnostic value of RFLP analysis in 19 of the 20 known Finnish families
Authors: Lehesjoki Anna‐Elina , Rasi Vesa , de la Chapelle Albert
Published: July 2010

With the aim of determining the usefulness of RFLP analysis in carrier detection and prenatal diagnosis, we studied all available members including 40 patients, 30 obligate carriers and 39 women at risk belonging to 19 out of a total of 20 Finnish hemophilia B families. The allele frequencies of the three intragenic polymorphisms studied (TaqI, XmnI and DdeI) did not differ significantly from those reported in other Caucasian populations. A considerable degree of linkage disequilibrium between the three polymorphisms was observed. Carriership evaluated in 39 females at risk led to exclusion in 14 while carriership was established in 5. The proportion of women who by pedigree analysis had a carriership risk between 10% and 90% could be reduced from 97% to 51% by RFLP analysis. Prenatal diagnosis using an intragenic polymorphism could potentially be offered to 69% of hemophilia carriers. DNAs from 19 unrelated patients were screened for mutations using a full‐length cDNA probe, but no abnormal hybridization patterns were observed. Our results indicate that RFLP segregation analysis provides a useful method of carrier detection and prenatal diagnosis in hemophilia B.
Congenital cardiovascular malformations (CCVM) and structural chromosome abnormalities: a report of 9 cases and literature review
Authors: Roskes Erik J. , Boughman Joann A. , Schwartz Stuart , Cohen Maimon M.
Published: July 2010

Nine cases of congenital cardiovascular malformations (CCVM) with associated unbalanced structural chromosomal abnormalities were ascertained in a population‐based study of heart defects, constituting 0.4% of the 2,103 cases of CCVM in the Baltimore‐Washington Infant Study (BWIS). This represents a four‐fold increase over the general population rate. In an effort to determine possible phenotype/karyotype correlations, the literature was searched for cases with similar karyotypic abnormalities. This comparison of 223 literature cases of karyotypic abnormalities with nine similar cases ascertained by heart malformation has provided the opportunity to review cardiac defects reported in cases of structural abnormalities of chromosomes 1, 3, 7, 8, 9, 10, 11, 15, and 18. The most common cardiac malformation present in the chromosomal cases was ventricular septal defect (VSD) (39%); similarly VSD is the most common CCVM among children with heart defects, although it is the primary defect in only 20% of the BWIS cases. Among all heart defects in the BWIS, atrial septal defect (ASD) represents 5.5% of all cases, but in cases of 8p duplication, ASD is present in 41%. In addition, 40% of cases of 9p duplication had an ASD. Similarly, 35% of cases of 11q duplication had an ASD. While the suggestion of specific karyotype/phenotype associations is premature, information on additional cases might clarify the possibility that genetic determinants related to septum formation may reside on chromosome 8, 9, and/or 11. The variety of chromosomal abnormalities in cases with ventricular septal defect indicates one type of genetic heterogeneity that may be involved in this very common heart defect.
Lacrimo‐auriculo‐dento‐digital (LADD) syndrome with renal and foot anomalies
Authors: Roodhooft A. M. , Brussaard C. C. , Elst E. , van Acker K. J.
Published: July 2010

A patient who presented with most features of lacrimo‐auriculo‐dento‐digital (LADD) syndrome, an autosomal dominant trait, is described. There was no deafness, and anomalies of the external ear and the upper limbs were discrete. Renal anomalies, consisting of progressive caliectasis with stone formation, were revealed by macroscopic hematuria. There were also skeletal anomalies of both feet, a feature not previously described. Renal and distal limb anomalies are probably features of LADD syndrome.
Reproductive planning after genetic counselling: a perspective from the last decade
Authors: Frets Petra G. , Niermeijer Martinus F.
Published: July 2010

Studies from the last decade on factors influencing reproductive planning after genetic counselling were reviewed. Increased possibilities of DNA‐analysis and prenatal diagnosis might have brought about a shift in the paramountcy of factors influencing reproductive planning after genetic counselling. In contrast to the literature in the seventies, the magnitude of the genetic risk was no longer found to be one of the decisive factors in postcounselling reproductive planning. Instead, the interpretation of the risk as high or low and the desire to have children appeared to be paramount. The impact of new developments in DNA‐analysis in prenatal diagnosis and presymptomatic testing will be an important subject for future studies on factors influencing reproductive planning.
Neurofibromatosis 2: a clinically and genetically heterogeneous disease? Report on 10 sporadic cases
Authors: Mayfrank L. , Wullich B. , Wolff G. , Finke J. , Gouzoulis E. , Gilsbach J. M.
Published: July 2010

Clinical and genetic data of 10 patients with neurofibromatosis 2 (NF‐2) are presented. Interestingly, no family history of neurofibromatosis was detectable in any of them, which indicates that these are sporadic cases of NF‐2, most likely due to a new mutational event. According to our own results and the data in the literature, sporadic cases of NF‐2 are clinically characterized by a high incidence of multiple meningiomas and spinal tumors in addition to the bilateral occurrence of acoustic neurinomas. The clinical heterogeneity of NF‐2 is pointed out and the possible existence of different forms of this disease is discussed.
Autosomal dominant craniosynostosis of the sutura metopica
Authors: Hennekam Raoul C. M. , van den Boogaard Marie‐Jose
Published: July 2010

Trigonocephaly due to craniosynostosis of the sutura metopica was found in two sibs with normal intelligence. Both were microcephalic. The father had a sloping forehead and possibly partial metopic craniosynostosis. The paternal grandfather had a bony ridge at the upper half of the metopic suture without significant head deformity. A paternal sister was possibly also affected. None of the affected persons showed significant other anomalies. Craniosynostosis of the metopic suture may be an autosomal dominantly inherited disorder, not associated with functional brain or other abnormalities.
Exclusion mapping of the Cohen syndrome gene from the Prader‐Willi syndrome locus
Authors: Kondo Ikuko , Hamabe Jun‐ichi , Yamamoto Kohtaro , Niikawa Norio
Published: July 2010

Karyotype and DNA analyses using DNA probes were carried out in a family with the Cohen syndrome. Two affected brothers had normal chromosomal constitutions. A major deletion or duplication of genomic DNA fragments hybridized with the DNA probes, pML34 at D15S9 locus and pTD3‐21 at D15S10 locus, assigned on 15q11‐q12 was not detected in the patients. In addition, a linkage of the syndrome to D15S9 and D15S10 loci was not observed in the family. These data suggest that a gene for the Cohen syndrome is excluded from the 15q11‐q12 region, on which a gene for the Prader‐Willi syndrome is assigned, and that the Cohen syndrome is distinctly different from the Prader‐Willi syndrome, although clinical manifestations of the Cohen and the Prader‐Willi syndromes are very similar.
Common intragenic and extragenic polymorphisms of blood coagulation factors VIII and IX are different in Chinese and Caucasian populations
Authors: de la Salle Corinne , Wu Qingyu , Baas Marie‐Jeanne , Hanauer André , Ruan Changgeng , Cazenave Jean‐Pierre
Published: July 2010

In order to examine the possibilities of carrier detection and prenatal diagnosis in hemophilia A and B in the Chinese region of Suzhou, we analyzed four different RFLPs within the factor IX gene and two intragenic RFLPs and one extragenic RFLP for the factor VIII gene. The results obtained show important differences between the Chinese and Caucasian populations. No polymorphism was found within the factor IX gene in the Chinese population and the informativity obtained for the factor VIII gene was quite different between the two populations for each RFLP studied.
Craniofrontonasal dysostosis: variable expression in a three‐generation family
Authors: Kere Juha , Ritvanen Annukka , Marttinen Eino , Kaitila Ilkka
Published: July 2010

A family with craniofrontonasal dysostosis (craniofrontonasal dysplasia) is described. There were three severely affected females, two of them daughters of apparently healthy parents. Examination of the male relatives revealed orbital hypertelorism and other minor anomalies in two of them, including the father of the two affected daughters. This family emphasizes the wide variation in the phenotype of craniofrontonasal dysostosis and suggests that male relatives with minor manifestations of the syndrome may be at high risk of having severely affected daughters. The expression of the gene may be modified by the sex.
Age of onset in vitiligo: relationship with HLA supratypes
Authors: Finco O. , Cuccia M. , Martinetti M. , Ruberto G. , Orecchia G. , Rabbiosi G.
Published: July 2010

HLA class I (A, B, C), class II (DR, DQ) histoglobulins and HLA class III (C4A, C4B and Bf) complement factors were analysed in 87 patients with vitiligo and in controls. Two HLA supratypes seem to mark different age of onset of vitiligo: HLA‐BfS, C4A3, C4B1, DR5 (W11), DQW3 is characteristic of the pediatric form; while HLA‐BfS, C4A3, C4B1, DR7, DQW2 marks the adult form of disease. The importance of defining HLA supratype, not single alleles, is discussed.
Inv dup (8) (p21.1 → 22.1): further case report and a new hypothesis on the origin of the chromosome abnormality
Authors: Gorinati Marino , Caufin Daniele , Minelli Antonella , Memo Luigi , Gaspardo Gianfranco , Dodero Andrea
Published: July 2010

We report a male infant with a de novo inverted duplication of bands 8p 21.1 → 22.1. The clinical features up to 8 months of age and the enzyme investigations are described. A new cytogenetic hypothesis on the genesis of this rare chromosome aberration is also discussed.
Tetrasomy 9p: an emerging syndrome
Authors: Jalal S. M. , Kukolich Mary K. , Garcia Mary , Benjamin Toni R. , Day Donald W.
Published: July 2010

An infant with non‐mosaic 9p tetrasomy is described. The tetrasomy apparently results from a translocation involving the 9qh region. All the cells analyzed from multiple banding techniques from lymphocyte culture as well as skin fibroblast culture were 9p tetrasomic. The infant, who had the characteristic dysmorphic features of 9p tetrasomy, survived for 2 months. Prominent features included: low birth weight, severe retardation, brachycephaly with large anterior fontanelle, hypertelorism with short bilateral palpebral fissures, beaked nose, bilateral cleft lip and palate, and low‐set, malformed ears. Skeletal anomalies, ambiguous genitalia and heart defect were also observed. These features are highly characteristic of the 9p tetrasomy syndrome based on six pure tetrasomy and four cases of tetrasomy that included part of the 9qh region.
Dizygotic twins concordant for truncus arteriosus
Authors: Lang Michael J. , Aughton David J. , Riggs Thomas W. , Milad Magdy P. , Biesecker Leslie G.
Published: July 2010

Persistent truncus arteriosus (TA) is an uncommon congenital cardiovascular malformation, which comprises between 0.4% and 4% of all congenital heart defects. Occurrence of TA in siblings has been reported infrequently. Twins concordant for isolated TA appear to have been reported only once previously. In this paper, we describe dizygotic twin females who were concordant for isolated TA.
Frequency of the phenylalanine deletion (ΔF508) in the CF gene of Belgian cystic fibrosis patients
Authors: Wauters Jan G. , Hendrickx Jan , Coucke Paul , Vits Lieve , Stuer Karel , van Schil Lutgard , van der Auwera Bart J. , Elsen August Van , Dumon Jan , Willems Patrick J.
Published: July 2010

Cloning and sequencing of the CF gene has identified a three‐base‐pair deletion (ΔF508) responsible for CF in the majority of CF patients (Kerem et al. 1989). We have used the polymerase chain reaction with oligonucleotide primers bridging the ΔF308 deletion to analyze the presence or absence of this mutation in the Belgian CF population. The ΔF306 mutation was present in 80% (57 on 71) of CF chromosomes from 36 unrelated Belgian CF families from the region of Antwerp. This mutation was associated with haplotype B for the KM.19–XV‐2c RFLPs as 93% (53 on 57) of the CF chromosomes with the Δ306 mutation carried haplotype B.
Unstable translocations: a new case?
Authors: Mattina T. , Milana G. , D'Agata A. , Conti L. , Sciacca F.
Published: July 2010

A female patient with Down syndrome due to unbalanced Robertsonian translocation (14;21) is reported. A different Robertsonian translocation involving a chromosome no. 14 was observed in her father, who was a carrier of a balanced Robertsonian t(13;14), while the maternal karyotype was normal. Hypotheses about the origin of the translocation in the daughter are discussed.
Hemophilia A: genetic prediction and linkage studies in all available families in Finland
Authors: Lehesjoki Anna‐Elina , Sistonen Pertti , Rasi Vesa , de la Chapelle Albert
Published: July 2010

RFLP studies were done in 82 (75%) of all known hemophilia A families in the Finnish population (approximately 5 million). Two intragenic RFLPs (BcII/F8A, Xbal/p482.6) and two extragenic markers (Taql/St14, BglII/DX13) were used. Among 263 females at risk, carriership could be evaluated with an intragenic marker in 47% and with an extragenic marker in 26%. In 27% of the females, carriership could be neither excluded nor confirmed; 68% of these females were relatives of an isolated patient. Eight recombinations between the factor VIII gene (F8C) and DXS52 (lod 25.02 at θ max 0.06), eight recombinations between F8C and DXS15 (lod 21.91 at θ max 0.05), and two recombinations between DXS52 and DXS15 (lod 33.56 at θ max 0.01) were found. Using multipoint linkage analysis, the most likely order of loci supported by the data was: F8C‐DXS15‐DXS52‐DXS134. RFLP segregation analysis provides a highly useful method of carrier detection and prenatal diagnosis of hemophilia A, but its limitations must be carefully taken into account.
Within‐individual variation in serum cholesterol levels: association with DNA polymorphisms at the apolipoprotein B and AI‐CIII‐AIV loci in patients with peripheral arterial disease
Authors: Monsalve M. V. , Robinson D. , Woolcock N. E. , Powell J. T. , Greenhalgh R. M. , Humphries S. E.
Published: July 2010

We have examined the association between variation at the apolipoprotein (apo) B gene and apo AI‐CIII‐AIV gene cluster and within‐individual variation in serum cholesterol levels. Annual measurements were available over a period of 5–10 years in a group of 117 male patients with peripheral arterial disease. The overall within‐individual coefficient of variation in cholesterol levels over time was 13.9%. For all patients, Restriction Fragment Length Polymorphism (RFLP) genotype at the apo B gene (Xbal and EcoRI) and apo AI‐CIII‐AIV gene cluster (XmnI, PstI and PvuII‐CIII) had previously been determined. At the apo B locus, individuals heterozygous for either the Xbal or EcoRI RFLP showed significantly greater within‐individual variability over time compared to individuals of other genotypes. At the apo AI‐CIII‐AIV gene cluster, individuals homozygous for the common allele of either the PstI or PvuIIA RFLPs showed the greatest within‐individual variability over time but there was no difference in this estimate associated with XmnI genotype. Our observations suggest that variation at both the apo B and apo AI‐CIII‐AIV loci interacts with unidentified environmental factors to determine individual variability in serum cholesterol levels over time.
Application of fluorescence in situ hybridization techniques in clinical genetics: use of two alphoid repeat probes detecting the centromeres of chromosomes 13 and 21 or chromosomes 14 and 22, respectively
Authors: Kølvraa S. , Koch J. , Gregersen N. , Jensen P. K. A. , Jørgensen A. L. , Petersen K. B. , Rasmussen K. , Bolund L.
Published: July 2010

Two cloned DNA fragments, one derived from an alpha satellite subfamily common to chromosomes 13 and 21, and the other derived from a similar subfamily common to chromosomes 14 and 22, have been used as biotinylated probes in in situ hybridization studies. Under high stringency conditions, chromosome specific centromeric labelling can be obtained. The applications of this technique in clinical situations are illustrated on metaphases from a fetus with trisomy 21, a fetus with trisomy 13, and a child with clinical features of cat‐eye syndrome.
Prader‐Willi syndrome and Robertsonian translocations involving chromosome 15
Authors: Casamassima Anthony C. , Shapiro Lawrence R. , Wilmot Patrick L. , Smith Karen Berk
Published: July 2010

A case of Prader‐Willi syndrome is presented in which high resolution chromosome analysis revealed not only a familial Robertsonian translocation (t(13q15q)], but also a del (15) (q11.2q13) of the chromosome 15 not involved in the translocation. While there have been numerous reports of Robertsonian translocations involving chromosome 15 in patients with Prader‐Willi syndrome, in this case, the Robertsonian translocation was shown to be unrelated to the clinical findings.
Automated multiple‐cell karyotyping: a clinical feasibility study
Authors: Lundsteen Claes , Gerdes Tommy , Maahr Jan
Published: July 2010

In order to increase the efficiency of the Magiscan metaphase location and karyotyping system, its software and mode of operation have been changed. In the new multiple‐cell karyotyping method, interactions by the operator are only required for relocation and counting of metaphases, but not for karyotyping. Metaphases are located and their coordinates recorded automatically as before. The first metaphase in the list is relocated, displayed on the screen, and counted by the operator. It is then karyotyped automatically while the operator relocates and counts the next metaphase in the list. This procedure continues until an appropriate number of metaphases have been counted and karyotyped. Finally a composite karyotype is printed out. Each karyotype is represented by a column of 23 chromosome pairs (1–22 and XX or XY) and all columns are lined up next to each other. Most chromosomes are correctly classified into the composite karyotype. Minor structural abnormalities are detected by comparing pairs of homologues. Overlapped, close touching, and grossly abnormal chromosomes are often misclassified or rejected and shown beneath the classified chromosomes. A trained cytotechnician can easily detect even small chromosome abnormalities on the composite karyotype. A clinical feasibility study indicates that the procedure can be used for routine cytogenetic analysis.
Metaphyseal acroscyphodysplasia
Authors: Verloes Alain , Merrer Martine Le , Farriaux Jean‐Pierre , Maroteaux Pierre
Published: July 2010

Based on two independent personal cases and a pair of sibs from the literature, we delineate a new category of bone dysplasia with cup‐shaped large metaphyses, for which the name metaphyseal acroscyphodysplasia is suggested. The main clinical features are severe growth retardation, micromelia predominating in the lower limbs, knee flexion, and severe brachydactyly. The radiological aspect of the knees is very specific: the lower femoral and upper tibial epiphyses embed themselves in their metaphyses, which are severely cup‐shaped. Premature central epiphyso‐metaphyseal fusion and gross deformation, or even coalescence, of the femoral condyles may occur. The femoral diaphyses are very short and broad, and there is progressive coxa valga. Bowed and/or short stubby tibiae with cone‐shaped metaphyses, and varus deformity of the tibio‐astragalian joint are other features. Slight deformations of the long bones occur in the upper limb. Severe brachydactyly, brachymesophalangy, phalangeal and metacarpal cone‐shaped epiphyses and irregular, bent and shortened diaphyses are the main signs of hand involvement. Psychomotor retardation is present in 3/4. Autosomal recessive inheritance is likely.
IBM‐PC compatible software for establishing metacarpophalangeal pattern profiles
Authors: Hosenfeld D. , Hosenfeld F. , Schaefer E. , Grote W.
Published: July 2010

We briefly present software for performing metacarpophalangeal pattern (MCPP) profile analysis, which runs on generally available low‐cost IBM (PC, XT, AT) and compatible PCs. The program is easy for the medical geneticist to handle and apply. We compared the mean MCPP of our own patients with Ullrich‐Turner syndrome with the mean MCPP for Ullrich‐Turner patients originally published by Poznanski.
A chromosome 17q de novo paracentric inversion in a patient with campomelic dysplasia; case report and etiologic hypothesis
Authors: Maraia Richard , Saal Howard M. , Wangsa Damrong
Published: July 2010

The campomelic syndrome is a skeletal dysplasia with a characteristic pattern of deformity involving the proximal and distal extremities, pelvic and shoulder girdles, thoracic cage and palate. Respiratory compromise often leads to death in early infancy. Etiology has not been determined although evidence suggests genetic heterogeneity in patients with campomelia. Cytogenetic analyses in the past have revealed an unexpectedly high incidence of a 46,XY karyotype in phenotypic females. We report here on a patient with a typical case of campomelic dysplasia in whom a de novo paracentric inversion of chromosome 17q was identified. Review of the genetic map of the inverted region identified potential “structural” genes including the Hox‐2‐homeobox gene and the collagen gene, COLlAl, which may be involved in the pathogenesis of campomelic syndrome.
Molecular identification of a small supernumerary marker chromosome by in situ hybridization: diagnosis of an isochromosome 18p with probe L1.84
Authors: Blennow Elisabeth , Nielsen Karen Bröndum
Published: July 2010

A dysmorphic child was found by cytogenetic analysis to have an extra small marker chromosome. The marker chromosome was shown to possess a chromosome 18 centromere by in situ hybridization, and probably represents an isochromosome 18p. Centromere specific probes should be of value in identifying extra small marker chromosomes, and thereby provide better understanding of the clinical significance of these.
Atelosteogenesis I and boomerang dysplasia: a question of nosology
Authors: Hunter A. G. W. , Carpenter B. F.
Published: July 2010

We report a patient whose clinical, radiologic and histopathologic findings are compatible with severe atelosteogenesis (AT‐I). The patient is compared with previously reported cases of AT‐I, as well as with patients reported as having “boomerang” dysplasia. We conclude that it is reasonable to consider AT‐1 and boomerang dysplasia as part of a spectrum, probably reflecting a common etiology. More and detailed clinical, radiologic and histopathologic reports are needed to further clarify the relationship of AT‐II and AT‐III in this family of skeletal dysplasias.
Identification of the 664 proline to leucine mutation in the low density lipoprotein receptor in four unrelated patients with familial hypercholesterolaemia in the UK
Authors: King‐Underwood Linda , Gudnason Vilmundur , Humphries Steve , Seed Mary , Patel Dilip , Knight Brian , Soutar Anne
Published: July 2010

Mutations in the gene for the low density lipoprotein (LDL) receptor cause Familial Hypercholesterolaemia (FH). One such mutation, a cytosine to thymine change in the codon for amino acid 664, causes proline (CCG) to be replaced by leucine (CTG) at this position, and creates a Pst I site in exon 14 of the gene. This mutation, previously identified in an FH homozygote of Asian Indian origin, results in a receptor with a reduced binding affinity for LDL and in delayed processing of the precursor form of the protein in cultured cells. A total of 224 unrelated heterozygous and 4 homozygous FH patients from London was screened for this mutation using direct amplification of genomic DNA by the polymerase chain reaction (PCR) and restriction digestion of the PCR product. Four patients were identified who were heterozygous for this mutation and the C to T base change was confirmed by sequencing. Affected relatives of these patients were also found to have the mutation. The effect of the mutation on LDL‐receptor function in lymphoblastoid cell lines obtained from two of these patients was similar to that observed in heterozygous relatives of the original proband (MM). Eight polymorphisms of the LDL receptor gene were used to determine the haplotype of the defective allele carried by the patients and the individual (MM) in whom the mutation was first discovered. Two different haplotypes were found, suggesting that the mutation, which occurs at a CpG ‘hotspot’, has arisen independently at least twice. The presence of the same single base change in the LDL‐receptor gene in several unrelated patients has not previously been reported in a population which is not geographically or culturally isolated.
Extra small marker chromosome associated with normal phenotype due to 3:1 disjunction of t(14;22) in a parent. Implications for the origin of marker chromosomes
Authors: Bröndum‐Nielsen Karen
Published: July 2010

A family with segregation of a translocation t(14;22) (q31;q11) is reported. The proband was ascertained by chromosome analysis after repeated spontaneous abortions in his wife. His normal sister was found to have the karyotype 47,XX,+der (22). The small size and banding pattern of chromosome 22 make it difficult to determine the breakpoint with certainty, but it was judged to be at q11. This small marker chromosome could thus be similar to the one found in the cat eye syndrome, and further studies may cast light on gene(s) involved in this syndrome.
Smith‐Lemli‐Opitz syndrome in female, monozygotic twins
Authors: Tzouvelekis G. , Antoniades K. , Batma A. , Nanas Ch.
Published: July 2010

A pair of monozygotic female twins with SLO syndrome is presented. We have found only one paper in the literature that referred to twins with this rare syndrome. The multiple congenital defects in these cases, consist of limb and genital abnormalities, retardation of growth, mental deficiency, craniofacial defects and abnormal neurological status.
Apolipoprotein B polymorphism and altered apolipoprotein B concentrations in Congolese blacks
Authors: Parra Henri‐Joseph , Martin F. , Monard F. , Ngangoué N. , Copin N. , Bard J. M. , Qafli M. , Dac N. Vu , Duriez P. , Fruchart J. C.
Published: July 2010

The immunoreactivity of apolipoprotein B (apo B) in plasma obtained from 238 unrelated black African male subjects from the People's Republic of Congo was analysed by non‐competitive Enzyme Linked‐Immunosorbent Assay (ELISA) with monoclonal BIP 45 anti‐LDL antibody. The polymorphism detected by BIP 45 monoclonal antibody is identical to the Ag(c,g) polymorphism. Antibody BIP 45 distinguishes three apo B allotypes (immunopheno‐types) encoded by the two allelic genes apo B Ag(c) and apo B Ag(g). Because of co‐dominant transmission, genotypes may be inferred from allotypes, and it has been shown that BIP 45 binds strongly to the Ag(c) factor and only weakly to the allelic Ag(g) factor. Analysis of the Congolese plasma samples indicated that 67.65% of them bound BIP 45 with low affinity (Ag(c‐,g+) genotype), 28.15% with intermediate affinity (Ag(c+,g+) genotype) and 4.20% with high affinity (Ag(c+,g‐) genotype). According to the Hardy‐Weinberg equilibrum, this corresponds to gene frequencies of 0.817 and 0.183 for the type Ag(g)/Ag(c) alleles, respectively. After adjustment for age and body‐mass index, it was found that the Ag(c) allele decreases the apo B level by 9.62 mg/dl and that the Ag(g) allele increases apo B by 0.43 mg/dl. Therefore, as much as 4.30% of the genetic variance for apo B level could be accounted for by the Ag(c,g) gene locus.
Saethre‐Chotzen syndrome (ACS III) in four generations
Authors: Niemann‐Seyde Susanne C. , Eber Stefan W. , Zoll Barbara
Published: July 2010

The acrocephalosyndactylies (ACS) are a group of inherited disorders characterized by premature fusion of cranial sutures in association with abnormalities of the hands and feet. Based on their clinical features, different types of ACS have been described. We here report on a family with 9 individuals affected with ACS III (Saethre‐Chotzen syndrome), 5 of them severely. Clinical features of the patients are presented with regard to differential diagnostic delineations.
Genetic epidemiology of cystic fibrosis in Saguenay‐Lac‐St‐Jean (Quebec, Canada)
Authors: Daigneault Jocelyne , Aubin Gervais , Simard Fernand , Braekeleer Marc De
Published: July 2010

Cystic fibrosis (CF) is an autosomal recessive disorder with a prevalence at birth estimated at 1/2000–1/2500 livebirths in Caucasian populations. Some 127 CF individuals are known in Saguenay‐Lac‐St‐Jean (SLSJ), a geographically isolated region of Quebec. The prevalence at birth was estimated at 1/902 live borns, and the carrier rate was estimated at 1/15 inhabitants in the SLSJ region. The mean inbreeding coefficient was only slightly elevated in the CF group compared with three control groups, and was due to remote consanguinity. The mean kinship coefficient was 2.4 times higher in the CF group than in the control groups. In SLSJ region, the places of origin of the CF individuals and their parents did not show a clustered nonuniform distribution. Endogamy was not higher in the CF group than in control groups.
Brachyolmia: a skeletal dysplasia with an altered mucopolysaccharide excretion
Authors: Sewell Adrian C. , Wern Christine , Pontz Bertram F.
Published: July 2010

A 15‐year‐old girl is described with brachyolmia. She presented with short‐trunked dwarfism, hypolordosis of the lower spine and radiological features of the disease. She was initially considered to have a mucopolysaccharidosis (type III Sanfilippo) on account of a pathological urinary glycosaminoglycan excretion pattern. The amount of urinary glycosaminoglycans was normal, but we found an increased amount of an undersulphated chondroitin sulphate molecule. Our finding of an undersulphated glycosaminoglycan points to a disturbance in chondroitin sulphate synthesis, and it is rare that a defect in glycosaminoglycan synthesis leads to a skeletal dysplasia. To our knowledge, this is the second case of brachyolmia with a possible defect in chondroitin sulphate‐sulphotransferase.
Familial Caffey's disease and late recurrence in a child
Authors: Borochowitz Zvi , Gozal David , Misselevitch Ines , Aunallah Jamal , Boss Johanan H.
Published: July 2010

Cortical Infantile Hyperostosis (Caffey's disease) is a benign and self‐limited disorder. Late recurrence or persistence of symptoms with deformity seems exceedingly rare. Its occurrence in isolated cases or in multiple members in families suggests the existence of two different forms, namely a sporadic form and a familial form. The tibia is the predominant bone known to be affected in the familial form, while the mandible is mostly affected in the sporadic form. The different pathological processes found in these two forms add further to the heterogeneity of this disorder. We describe an Arabic‐Christian, non‐consanguineous family with two affected sibs. In one, recurrent Caffey's disease was diagnosed at the age of 11 years.