bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural tube defects and omphalocele in trisomy 18
Authors: Moore Cynthia A. , Harmon Joseph P. , Padilla Lillie‐Mae , Castro Virgilio B. , Weaver David D.
Published: July 2010

A trisomy 18 fetus with severe congenital anomalies including craniorachischisis, large omphalocele, and bilateral cleft lip and palate is reported. The occurrence of neural tube defects and/or omphalocele in reported cases of trisomy 18 is discussed and the frequency of these anomalies in 85 trisomy 18 patients evaluated at Indiana University School of Medicine from 1963 to 1986 is reviewed. In this series of patients the frequency of neural tube defects was 7.0% and the frequency of omphaloceles was 5.9%. The percentage of these findings in our cases supports the premise that neural tube defects and omphaloceles are part of the trisomy 18 phenotype. Since fetuses with trisomy 18 are subject to early fetal loss or premature birth, the more subtle physical features of this condition may not be apparent. Thus, karyotyping of fetuses and premature infants with either neural tube defect or omphalocele should be considered.
Genetic counselling in a case of TAR syndrome where the father presented malformations of the feet
Authors: Le Marec B. , Odent S. , Bracq H. , Roussey M. , Le Gall E. , Gandon Y.
Published: July 2010

TAR syndrome is usually an autosomal recessive disease; we report a family where the father of the propositus presented malformations of the feet, and review the known cases involving several generations. The authors of these cases concluded that the TAR syndrome is probably genetically heterogeneous.
Genetic counselling in hypomelanosis of Ito: case report and review
Authors: Moss Celia , Burn John
Published: July 2010

A 27‐year‐old male with hypomelanosis of Ito (HI) is reported. One of his two children had a postaxial ray defect of one leg but neither had cutaneous features of HI. Somatic mosaicism for a gene defect lethal to ectodermal derivatives offers the best explanation for HI in males, with consequent negligible recurrence risk. The limb defect is considered coincidental. The excess of girls with HI could be due to a female cohort with incontinentia pigmenti (IP) which may be indistinguishable: counselling of females must therefore take account of possible X‐linked inheritance.
Karyotyping urine sediment cells confirms trisomy 12 mosaicism detected at amniocentesis
Authors: Leschot Nico J. , Wilmsen‐Linders Ellen J. M. , van Geijn Herman P. , Samsom Janny F. , Smit Leo M. E.
Published: July 2010

A newborn is described in whom trisomy 12 mosaicism was detected prenatally at third trimester amniocentesis during the fourth pregnancy of a 34‐year‐old woman. After birth, trisomy 12 cells were found in placental tissue and in cultured urine sediment cells. A sample of cord blood and a skin biopsy revealed only normal (46,XX) cells. Both parents had a normal karyotype. After a difficult start with unexplained hypoglycaemias and convulsion equivalents, the girl is doing well at the age of 9 months: there are no signs of central motor disturbance. The importance of the use of cultured urine sediment cells in confirming chromosomal mosaicism is stressed.
Acid α‐neuraminidase deficiency: a nephropathic phenotype?
Authors: Roth Karl S. , Chan James C. , Ghatak Nitya R. , Mamunes Peter , Miller William W. , O'Brien John S.
Published: July 2010

Isolated neuraminidase deficiency is a member of the relatively rare group of storage disorders known as glycoproteinoses. We report the long‐term natural history of the disease in one of the first patients described in the literature. An unusual feature of the disease is the abrupt onset and fulminant nature of the nephrotic syndrome, complications of which caused the demise of our patient. Pathological examination of the kidneys from this child revealed renal epithelial cell damage, most marked in the membranes of the glomeruli and proximal tubules, findings which are consistent with the high sialic acid content of the membrane in these areas of the nephron. Chemical analysis indicated that the bulk of the stored material in the kidney was in the form of polar sialyloligosaccharides of high molecular weight. On the basis of our experience, as well as the previous reports of neuraminidase‐deficient patients with nephropathy, we propose a nephropathic phenotypic variant of type 2 infantile sialidosis.
Four copies of 8p in a mentally retarded boy with the mosaic karyotype 47,XY, +i(8p)/46,XY
Authors: Kristoffersson Ulf , Lagergren Jan , Heim Sverre , Mandahl Nils
Published: July 2010

A 5‐year‐old boy with slow psychomotor development, slight widening of the posterior part of the brain ventricles, and anomalies of vertebrae and ribs is described. Cytogenetic investigation revealed the mosaic karyotype 47,XY, +i(8p)/46,XY, i.e., a triplication of 8p. This abnormality has not been reported before.
Infantile autism, fragile (X) (q27.3) and RFLP analysis in an extended Swedish family
Authors: Anvret Maria , Gillberg Christopher , Wahlström Jan , Albertsson‐Wikland Kerstin , Davies Kay
Published: July 2010

In an extended family with eight individuals with infantile autism, in association with other developmental disorders and fragile (X) (q27.3), DNA techniques were used to investigate linkage between X chromosomal probes and the disorder. F9 was not informative and recombination was found between fragile X and DXS15, DXS51 and DXS52.
Ataxia‐without‐telangiectasia in two sisters with rearrangements of chromosomes 7 and 14
Authors: Maserati Emanuela , Ottolini A. , Veggiotti P. , Lanzi G. , Pasquali F.
Published: July 2010

Two sisters, 11 and 9 years old respectively, had the clinical features of a progressive neurological disorder similar to the ataxia‐telangiectasia (AT) syndrome. The two patients have ataxia and chromosome instability with rearrangements of chromosomes 7 and 14 but no telangiectasia, nor the range of immunological anomalies typical of AT. Comparison with similar cases from the literature leads to the conclusion that either there is a specific disorder characterized by ataxia‐without‐telangiectasia and with the same cytogenetic pattern of AT, or AT shows a wider variability of phenotypic expression than thought before.
Effects of arachidonic acid and inhibitors of arachidonic acid metabolism on phagocyte‐induced sister chromatid exchanges
Authors: Weitberg Alan B.
Published: July 2010

Stimulated human phagocytes produce toxic oxygen radicals which induce sister chromatid exchanges in cultured mammalian cells. Oxidative damage to membranes initiates lipid peroxidation chain reactions and stimulation of the arachidonic acid cascade. The products of these reactions may mediate the genetic toxicity of oxygen radicals. Arachidonic acid significantly augmented the number of sister chromatid exchanges in target cells exposed to stimulated phagocytes. This genetic damage was abrogated in radical‐treated cells preincubated with inhibitors of the cyclooxygenase (indomethacin), lipoxygenase (nordihydroguaiaretic acid) or both (piroxicam) pathways.
Clinical features in a de novo interstitial deletion 15q13 to q15
Authors: Autio Seppo , Pihko Helena , Tengström Carola
Published: July 2010

A boy with several dysmorphic features and suffering from mental and motor retardation was found to have a de novo interstitial deletion of chromosome 15, involving bands q13 to q15. His clinical picture is described and compared with the clinical features reported in other deletions of this chromosome, located or extending distally from the region associated with Prader‐Willi syndrome.
Homozygosity for the transthyretin‐met30‐gene in two Swedish sibs with familial amyloidotic polyneuropathy
Authors: Holmgren G. , Haettner E. , Nordenson I. , Sandgren O. , Steen L. , Lundgren E.
Published: July 2010

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder. Recent biochemical studies have revealed that amyloid protein in FAP of Japanese, Swedish and Portuguese origin mainly consists of a variant transthyretin (TTR) (formerly called prealbumin) with one amino acid substitution of methionine for valine at position 30. In a 56‐year‐old man with typical polyneuropathy, gastrointestinal problems and vitreous amyloid, we diagnosed homozygosity for the TTR‐met30‐gene using RFLP analysis. In a family study, a sister presented the same homozygous RFLP pattern; however, in a careful clinical investigation we were not able to demonstrate any of the typical symptoms of FAP, nor could we demonstrate amyloid deposits in a biopsy skin specimen. This is the first report of homozygosity for the TTR‐met30‐gene, and it shows that the mutation of the protein involved in amyloid formation may be necessary but is clearly not sufficient for the clinical symptoms.
Further evidence for an association between the Xbal polymorphism at the apolipoprotein B locus and lipoprotein level
Authors: Leren Trond P. , Berg Kåre , Hjermann Ingvar , Leren Paul
Published: July 2010

Subjects with non‐familial hypercholesterolemia who were homozygous for absence of an Xbal restriction site in the apolipoprotein B gene (genotype X2X2) had significantly lower values of apolipoprotein B than those possessing the site. Our data are in agreement with those of Berg (1986) and Law et al. (1986) indicating that X2X2 homozygotes have lower levels of apolipoprotein B, total serum cholesterol, triglycerides and LDL cholesterol. The mechanism underlying this effect is unknown, but could reflect different LDL metabolism between subjects with different genotypes.
Rates and survival of individuals with trisomy 13 and 18 Data from a 10‐year period in Denmark
Authors: Goldstein Henri , Nielsen Kim Gjerum
Published: July 2010

Rates and survival figures for trisomy 13 and trisomy 18 have been calculated for Denmark (DK) based on a 10‐year period (1977–86). The data have been ascertained through The Danish Central Cytogenetic Register, all cytogenetic laboratories in DK, paediatric departments throughout the country, The Medical Birth Register and The Register of Causes of Death in DK. Nineteen liveborn probands with trisomy 13 and 76 liveborn probands with trisomy 18 were found. No stillborn cases with trisomy 13 but 6 with trisomy 18 were found. By prenatal diagnosis 19 probands with trisomy 13 and 46 with trisomy 18 were found. Based on liveborn and stillborn probands, the prevalence at birth was 1 per 29374 for trisomy 13 and 1 per 6806 for trisomy 18. The median survival for trisomy 13 was 2.5 days, while the same figure for trisomy 18 was 6.0 days. The rates calculated seem rather low compared to earlier studies.
A de novo interstitial deletion of chromosome 6 (q22.2q23.1)
Authors: Park Jonathan P. , Graham John M. , Berg Susan Z. , Wurster‐Hill Doris H.
Published: July 2010

A unique interstitial deletion of the long arm of chromosome 6 involving bands q22.2 and q23.1 was observed in a patient referred for craniostenosis and developmental delay. The associated phenotypic anomalies are compared with other reported cases of deletion 6q involving adjacent regions.
Translocation t(13;14) in nine generations with a case of translocation homozygosity
Authors: Eklund A. , Simola K. O. J. , Ryynänen M.
Published: July 2010

The Robertsonian translocation t(13;14) (p11;q11) was studied in three families with probable common ancestry in Eastern Finland. In the largest family the translocation has segregated through at least nine generations. The same family also included a female who was homozygous for t(13;14). No clear‐cut effect of the translocation on fertility could be demonstrated and only one case of trisomy 13 was recorded in the offspring of t(13;14) carriers. The results are discussed, with implications for human chromosomal evolution.
Clinical findings in 12 patients with MPS IV A (Morquio's disease)
Authors: Nelson J. , Broadhead D. , Mossman Jean
Published: July 2010

Clinical heterogeneity in MPS IV A (Mucopolysaccharidosis IV A, Morquio Disease Type A) has become more clearly identified in recent years. The clinical findings in 12 cases of MPS IV A are described. Clinical presentation was variable, and some cases were only mildly affected. All showed deficiency of N‐acetylgalactosamine‐6‐sulphate sulphatase in fibroblasts, but the patient with the mildest clinical presentation showed a high residual enzyme activity. The urinary glycosaminoglycans (GAGs) were examined on all patients by a two‐dimensional electrophoresis technique which proved to be highly reliable and efficient. In particular, no false negative results were obtained, a problem often encountered with routine screening methods. These cases support the division of MPS IV A into three subgroups: the severe “classical” type, an intermediate type and a mild type, all caused by N‐acetylgalactosamine‐6‐sulphate sulphatase deficiency. Residual enzyme activity may be an important prognostic indicator.,
Clinical findings in 12 patients with MPS IV A (Morquio's disease)
Authors: Nelson J. , Kinirons M.
Published: July 2010

Typical dental changes were present in all cases, although they were of variable degree. However, the tooth morphology would appear to be highly specific for MPS IV A, and is not found in MPS IV B (β‐galactosidase deficiency) or the recently delineated MPS IV C (enzyme defect unknown). Thus the dental changes have a very useful diagnostic potential in mild atypical cases of MPS IV A, although they may only be demonstrable radiologically in some such cases.
Clinical findings in 12 patients with MPS IV A (Morquio's disease)
Authors: Nelson J. , Thomas P. S.
Published: July 2010

Odontoid dysplasia in the absence or presence of atlanto‐axial instability was found in all cases. In general, this correlated well with the overall clinical severity of the condition and illustrates the importance of careful follow‐up of these patients. Symptoms or signs of cervical cord compression merit further investigation. Proven compromise of the upper cervical cord is an indication for posterior fusion of the upper cervical spine.
Microdeletions in patients with X‐linked muscular dystrophy: molecular‐clinical correlations
Authors: Lindlöf M. , Kääriäinen H. , van Ommen G. J. B. , de la Chapelle A.
Published: July 2010

The DNA from 68 patients with X‐linked (Duchenne and Becker) muscular dystrophy belonging to 49 unrelated families was analyzed for microdeletions using 13 closely linked or gene‐specific DNA‐markers. Fourteen patients from eight families showed a deletion involving at least one of the markers used, giving a deletion frequency of 16%. The proportion of families with deletions was 36% in the Becker and 8% in the Duchenne form of the disease. With one exception, the extent of the deletion was different in different families. All living, affected males from the same family carried the same deletion. The extent or the localization of the deletion did not correlate with clinical features such as severity of disease or mental retardation.
Discriminant analysis of dermatoglyphic measurements in fragile X males and females
Authors: Loesch Danuta Z.
Published: July 2010

Two hundred and eight fragile X subjects (92 males and 116 females) and matched Australian (60 males and 32 females) and British (122 males and 118 females) normal samples were used to calculate 4 discriminant functions, based on dermatoglyphic measurements. The most efficient discriminating variables between fragile X and normal males, selected by means of the Wilk's stepwise method, included: ridge counts on fingers 1–3, the hallucal (f) count on soles, the atd angle, and pattern intensities in palmar areas 2, 4 and 5 as well as on fingers 4 and 5. In females, the ridge breadth, the hallucal (e) count, the atd angle and pattern intensities in palmar areas 3–5 as well as on fingers 1, 3 and 5 comprised the final discriminant. The misclassification rate based on distributions of individual discriminant scores in each pair of samples, and on prior probabilities, was lowest (16.8%) in fragile X males compared with the Australian normal subjects. In both female comparisons, this rate approached 44%. A bias to misclassification rates resulting from various analytical procedures and some properties of the data are discussed. We conclude that the discriminant function based on dermatoglyphic measured variables alone is not good enough for assessing carrier probabilities for fragile X, especially in females. However, we have been able to select the best discriminators which may be used, together with other measured body characteristics, to obtain a more powerful discriminant function. Moreover, a consideration of discriminant scores based on dermatoglyphic traits only may help in estimating carrier probabilities. We propose that the discriminant function based on such scores is most appropriate for use as a dermatoglyphic diagnostic index, since indices which are derived from frequencies of binary traits tend to understimate misclassification rates.
Association between epitopes detected by monoclonal antibody BIP‐45 and the Xbal polymorphism of Apolipoprotein B
Authors: Dunning Alison M. , Duriez P. , Dac N. Vu , Fruchart J. C. , Humphries Steve E.
Published: July 2010

An epitope of Apolipoprotein B (ApoB), recognised by a monoclonal antibody BIP‐45, is associated with the development of ischaemic heart disease (Duriez et al. 1988). We have examined the genetic relationships between this epitope and three Restriction Fragment Length Polymorphisms (RFLPs) of the gene for ApoB detected with the enzymes EcoRI, PvuII and XbaI in a sample of 53 unrelated individuals from France. There is an association between binding affinity to BIP‐45 and the XbaI RFLP; the 8.6kb XbaI allele (absence of cutting site) being associated with low‐affinity binding to BIP‐45. In this sample of individuals there is no significant association between serum cholesterol levels and BIP‐45 binding affinity, but there is a significant correlation between serum cholesterol levels and XbaI genotype, with individuals of the genotype XIXI having the highest and those with the genotype X2X2 having the lowest levels of serum cholesterol. This suggests that variation at the ApoB locus may be involved independently in the determination of serum lipid levels and in the development of ischaemic heart disease.
Chromosomal imbalance in the offspring of translocation carriers involving 7p
Authors: Gabarrón J. , Glover G. , Jiménez A. , Salas P. , Pérez‐Bryan J. , Parra M. J.
Published: July 2010

Five families with balanced translocations involving 7p are reported. Three girls from two of these families presented several congenital malformations and partial trisomy 7p. A comparison is made of their phenotype with other reported cases.
Follow‐up of 30 Klinefelter males treated with testosterone
Authors: Nielsen Johannes , Pelsen Bjarne , Sørensen Kurt
Published: July 2010

Thirty Klinefelter males treated with testosterone were studied by a follow‐up examination carried out an average of 3.6 years after treatment began. The age of the men averaged 25.5 years at the time of the follow‐up. Seventy‐seven per cent of the men were judged to have benefited from testosterone treatment. They showed better mood, less irritability, more energy and drive, less tiredness, more endurance and strength, less need for sleep, better concentration ability and better relations with others during testosterone treatment. The beneficial effects of testosterone persisted in some of the men after cessation of treatment. The findings show that Klinefelter males given testosterone for the first time as adults can benefit from such treatment, even though it is preferable to start treatment at the age of 11–12 years.
Km mutant of acid α‐glucosidase in a case of cardiomyopathy without signs of skeletal muscle involvement
Authors: Suzuki Yoshiyuki , Tsuji Akihiko , Omura Kiyoshi , Nakamura Gen , Awa Shoichi , Kroos Marian , Reuser Arnold J. J.
Published: July 2010

A male patient is reported with a mutation of acid α‐glucosidase causing an altered Km toward natural substrates. Cardiac arrhythmia was found at 12 years of age, and he died of heart failure at 15 years. No skeletal muscle involvement was observed either clinically or histologically. Acid α‐glucosidase activity in fibroblasts was moderately low (43% of the control mean) with normal Km for 4‐methylumbelliferyl α‐D‐glucoside. The hydrolysis of glycogen was markedly decreased (14% of the control mean), and the Km for maltose was increased 4‐fold and for glycogen 5‐fold. The biosynthesis and the posttranslational processing of the mutant enzyme appeared normal, but the total amount of the enzyme was lower than normal. This mutant enzyme comigrated with normal acid α‐glucosidase on starch gel electrophoresis, and not with the rare isozyme, acid α‐glucosidase 2. A possible role of this mutant enzyme in the pathogenesis of this disease and the relationship to glycogenosis II are discussed.
Partial trisomy 20q due to paternal t(8;20) translocation: Case report and review of the literature
Authors: Pierquin G. , Herens C. , Dodinval P. , Frederic J. , Weber I. , Senterre J. , Fryns J. P.
Published: July 2010

In this report we present a malformed female newborn with partial trisomy 20q who was the unbalanced product of a paternal 8p/20q translocation (46,XY,t(8;20) (p23.1;q11)).
X‐linked recessive aqueductal stenosis without macrocephaly
Authors: Kelley Richard I. , Mennuti Michael T. , Hickey William F. , Zackai Elaine H.
Published: July 2010

A normocephalic, severely retarded boy with a family history suggesting aqueductal stenosis was found by computerized tomography to have aqueductal stenosis. His parents' concurrent pregnancy was monitored by ultrasonography and amniocentesis; these disclosed a male fetus which developed marked hydrocephalus after the 20th week. The pregnancy was terminated and an autopsy of the fetus demonstrated several major CNS malformations in addition to a very narrowed aqueduct. This case illustrates the diffuse CNS disease present in at least some cases of X‐linked aqueductal stenosis (XLAS) and the importance of considering this variable syndrome in normocephalic, non‐dysmorphic mentally retarded males. Important aspects of the prenatal diagnosis of XLAS are also illustrated.
Carrier detection in Sanfilippo A syndrome
Authors: Toone J. R. , Applegarth D. A.
Published: July 2010

Leucocytes or fibroblasts from 10 obligate heterozygotes for Sanfilippo A syndrome gave decreased heparan N‐sulphatase levels, using a modification of the method of Hall et al. (1978), which did not overlap normal control values. Five family members gave decreased values and are presumed heterozygotes.
Amniotic fluid folate, vitamin B12 and transcobalamins in neural tube defects
Authors: Gardiki‐Kouidou P. , Seller Mary J.
Published: July 2010

Levels of folate, vitamin B12, the vitamin B12 binding proteins, apotranscobalamin I, II and III (TC I, II and III) and the unsaturated vitamin B12 binding capacity (UBBC) were measured in mid‐trimester amniotic fluids from normal pregnancies, and from those where the fetus had open spina bifida, anencephaly or omphalocoele, and where the fetus was normal but the mother had had a previous neural tube defect pregnancy. At 15–19 weeks' gestation, vitamin B12 levels were low in the fluids of all the types of abnormal fetuses, and also of normal fetuses where there had been a previous NTD sib. In contradistinction, TC I, II and III and UBBC levels were generally abnormally high in all these groups. Low vitamin B12 levels in the face of high carrier protein levels suggest deranged vitamin B12 production or transport. Since these abnormalities are present in fluids from normal sibs of NTD individuals as well as from those with midline lesions, an inherited defect is implied. We propose that at least part of the genetic predisposition to NTD, and possibly other midline defects, could reside in an abnormality connected with vitamin B12 production, transport or metabolism, and a mechanism is suggested.
Unusual segregation in a family with a 11/21 translocation
Authors: Steensen Pernille , Ford Judith Helen , Lillquist Kaj , Friedrich Ursula
Published: July 2010

A familial 11/21 translocation is described where the proband has an unbalanced translocation and the oldest translocation carrier shows mosaicism with a partial trisomy no. 21.
Familial recurrent dislocation of patella with autosomal dominant mode of inheritance
Authors: Borochowitz Zvi , Soudry Michael , Mendes David G.
Published: July 2010

Recurrent dislocation of the patella is considered to be a manifestation of generalized joint laxity. An autosomal dominant mode of inheritance was previously suggested in a few instances; however, male‐to‐male transmission has not yet been reported. We report a recurrent dislocation of the patella occurring in five generations of one family with male‐to‐male transmission and without generalized joint laxity.
First trimester prenatal evaluation for I‐cell disease by N‐acetyl‐glucosamine 1‐phosphotransferase assay
Authors: Ben‐Yoseph Yoav , Mitchell Deborah A. , Nadler Henry L.
Published: July 2010

First trimester prenatal diagnosis was offered to a couple at risk for having a child with I‐cell disease (mucolipidosis II). The prenatal evaluation was based for the first time on examination of N‐acetylglucosamine 1‐phosphotransferase activity, deficiency of which is the primary biochemical defect in both I‐cell disease and pseudo‐Hurler polydystrophy (mucolipidosis III). Heterozygote levels of this enzyme activity were determined in chorionic villi obtained at 9 weeks of gestation, as well as in cultured trophoblasts derived from this specimen, and led to the diagnosis of an unaffected fetus. This procedure has advantages over that based on detection of abnormal intracellular‐extracellular distribution of lysosomal enzyme activities, which is expressed only in homozygotes and fully expressed only in cell culture specimens.
Partial deletion of 4p in fetal cells not present in chorionic villi
Authors: Eiben Bernd , Leipoldt Michael , Schübbe Ingrid , Ulbrich Rainer , Hansmann Ingo
Published: July 2010

A case of a prenatal diagnosis at the second trimester is presented showing a normal karyotype in 12 metaphases from chorionic villi. In all cultured amniotic cells, however, and also in all fetal fibroblasts analyzed after abortion a structural anomaly (46,XY;del 4(pter→p15.2) was detected. Prenatal diagnosis was performed because of intrauterine growth retardation, cleft lip and esophagus atresia by ultrasound. The fetal stigmata are compatible with the Wolf Hirschhorn syndrome. We conclude that amniocentesis may be indicated notwithstanding a normal CV‐diagnosis in those rare pregnancies with a characteristically abnormal ultrasound.
Emery‐Dreifuss syndrome and X‐linked muscular dystrophy with contractures: evidence for homogeneity
Authors: Goldblatt J. , Schram L. J. , Wallis G. , Oswald A. , Beighton P.
Published: July 2010

We report on a family in which individuals have clinical features of both Emery‐Dreifuss syndrome (EMD) and X‐linked muscular dystrophy with contractures (XLMDC). Molecular studies on this kindred showed linkage between the disorder and probe DXS 52 (St 14) located at Xq28. The gene for conventional EMD has previously been mapped to this region and our molecular findings therefore suggest that EMD and XLMDC represent the phenotypic spectrum of the same mutated gene rather than heterogeneity, as sometimes postulated.
Childhood manifestation of autosomal dominant polycystic kidney disease: no evidence for genetic heterogeneity
Authors: Gal Andreas , Wirth Brunhilde , Kääriäinen Helena , Lucotte Gerard , Landais Paul , Gillessen‐Kaesbach Gabriele , Müller‐Wiefel Dirk E. , Zerres Klaus
Published: July 2010

Autosomal dominant polycystic kidney disease (ADPKD) usually becomes symptomatic between the third and fifth decades. We studied ten families segregating for ADPKD in which children were observed with typical manifestations of the disease at birth or in early childhood. In these families, linkage analysis was carried out with a cloned DNA sequence from the alphaglobin locus known to be closely linked to the disease gene in adult onset ADPKD. In the families studied here, close linkage (θmax= 0.09 at Zmax= 2.32) was also observed between the marker and disease loci. These results provide no evidence for genetic heterogeneity of ADPKD in families with early and adult onset.
Growth, bone maturation and pubertal development in children with the EMG‐syndrome
Authors: Sippell W. G. , Partsch C.‐J. , Wiedemann H. R.
Published: July 2010

In 7 patients (5 girls, 2 boys) with the EMG or Wiedemann‐Beckwith syndrome, statural growth, bone age (BA), weight and pubertal development were studied longitudinally. Height was above the 90th percentile (%) for chronological age (CA) after age 2 years, reaching an average of 2.5 SD above the mean at or after puberty. Adult or attained height also exceeded significantly (P<0.015) parental (genetic) target height by 13.2 cm on the average. In one girl, adult height prognosis (190 cm) could be reduced to an adult height of 183 cm by high‐dose estrogen treatment. In most children, growth velocity remained above the 90th % up to 4–6 years of age and normalized thereafter. In all patients studied, bone age was markedly advanced and particularly so during the first 4 years after birth. Weight was above the 90th–97th % during infancy and early childhood and remained there, appropriate or slightly subnormal for height, until adulthood, except for 3 girls who reached and maintained the 50th % during or after puberty. Spontaneous pubertal development occurred within normal limits for CA and around the 50th % for BA. Except for the marked bone age acceleration, the reason for the increased statural growth and adult height in patients with the EMG syndrome is still unknown.
Bloom's Syndrome. XII. Report from the Registry for 1987
Authors: German James , Passarge Eberhard
Published: July 2010

Bloom's syndrome has been known as a clinical entity for 34 years. Careful records of cases diagnosed throughout the world have been maintained since its recognition as an entity, and most instances of cytologically verified Bloom's syndrome have been accessioned to what has been referred to as the Bloom's Syndrome Registry since the mid‐1960s. Presented here is the fourth in a series of progress reports from the Registry of information accumulated during this long‐term surveillance of affected families, along with mention of selected recent advances that have been made in the understanding of the syndrome. 130 persons had been accessioned to the Registry by the end of 1987; 96 of these were alive, their mean age being 18.9 years. Although a number of clinical complications occur in Bloom's syndrome, the most important is malignant neoplasia. In the 130 persons in the Registry, 57 malignant neoplasms had been detected, the mean age at diagnosis being 24.8 years. Neoplasia in Bloom's syndrome is noteworthy not only because of its frequency and exceptionally early age of emergence but for its variety of histological types and sites of origin.
A case of prenatal diagnosis of a familial satellited Yq chromosome
Authors: Tsita K. P. , Vallas O. S. , Velissariou P. J. , Lyberatou‐Moraitou E. K.
Published: July 2010

A case of a fetus with a satellited Yq revealed during prenatal diagnosis because of advanced maternal age is presented. This case is the 18th reported in the literature. Cytogenetic studies in the father, uncle and grandfather of the fetus revealed that the Yqs was inherited and the possible mechanisms of origin are discussed.
Bloom's syndrome. XIV. The disorder in Japan
Authors: German James , Takebe Hiraku
Published: July 2010

Fourteen persons have been diagnosed Bloom's syndrome in Japan, with cytological verification in 11. Widely separated birthplaces throughout Honshu, Shikoku, and Kyushu and a parental consanguinity incidence greater than in the general population suggest that the Bloom's syndrome mutation, although very rare, is distributed widely throughout the Japanese population. The locus mutated is the same as in Jews and persons of Western European extraction. The phenotype differs somewhat from most cases recognized elsewhere, in that dolichocephaly is a less constant feature, the facial skin lesion is less prominent, and life‐threatening infections are less common. The characteristic predisposition to neoplasia exists, however, as probably does that to diabetes mellitus.
Dual porphyria in double heterozygotes with porphobilinogen deaminase and uroporphyrinogen decarboxylase deficiencies
Authors: Doss Manfred O.
Published: July 2010

A coexistent dual deficiency of porphobilinogen deaminase (PBG‐D; EC 4.3.1.8) and uroporphyrinogen decarboxylase (EC 4.1.1.37) in erythrocytes was recognized in five individuals, four males and one female. Clinically, the female and one male were diagnosed as suffering from acute intermittent porphyria (AIP), and the other two males were diagnosed as having porphyria cutanea tarda (PCT). Biochemically, the excretion pattern of urinary and fecal heme precursors exhibited a complex constellation with signs characteristic for both AIP and PCT. A coexistent dual enzyme deficiency of PBG‐D and URO‐D could be confirmed by repeated studies over 10 years. Clinical courses of both disease manifestations were observed. Family investigations have shown that the two disorders do not consistently segregate together. The findings suggest that the dual porphyria reflects a double heterozygous condition of coexistent AIP and PCT genes in the same individual.
Perinatal and first year follow‐up of patients with Prader‐Willi syndrome: normal size of hands and feet
Authors: Chitayat David , Davis Ellen B. , McGillivray Barbara C. , Hayden Michael R. , Hall Judith G.
Published: July 2010

Four patients with Prader‐Willi syndrome, diagnosed in the neonatal period and followed during the first year of life, are reported. There were three males and one female. All four patients presented with hypotonia and distinct craniofacial dysmorphism. Prometaphase chromosome analysis showed interstitial deletion of 15q in all of them. The placentae and umbilical cords were examined in three of the patients and found normal. Electromyography done in the neonatal period suggested primary myopathy. Height, weight and head circumference were normal at birth in all patients. Hand and foot measurements showed normal size at birth and during the first year of life.
Brachydactyly type A‐7 (Smorgasbord): a new entity
Authors: Meiselman Samuel A. , Berkenstadt Michal , Ben‐Ami Tami , Goodman Richard M.
Published: July 2010

We report a family with a form of brachydactyly that involves characteristic features of types A2 and D brachydactyly plus features found in other types of brachydactyly and also features not previously noted. This set of findings represents a new syndrome, which we have termed brachydactyly type A7 (Smorgasbord).
An interstitial deletion of the long arm of chromosome 13
Authors: Roland B. , Lowry R. B. , Robertson A. S. , Cox D. M.
Published: July 2010

A case of an interstitial deletion of chromosome 13, identified as 46,XY,del(13)(q22q31), is reported in a child with psychomotor retardation, prominent low‐set ears, epicanthus, hypertelorism, broad nasal bridge, hypoplastic fifth fingers and abnormal dermatoglyphics. This patient is compared to others in the literature with a similar deletion.
A 45,X/69,XXY fetus
Authors: Betts David R. , Fear Claudine N. , Barby Teresa , Seller Mary J.
Published: July 2010

Post‐mortem examination of a 20‐week fetus showed incompletely masculinised external genitalia, hypoplastic adrenal glands and minor physical stigmata suggestive of a chromosome abnormality. Gonad and skin were karyotyped and both were found to contain two cell lines, 45,X and 69,XXY. It appears this fetus is a true 45,X/69,XXY mosaic.
Linkage between serum cholinesterase 2 (CHE2) and γ‐crystallin gene cluster (CRYG): assignment to chromosome 2
Authors: Eiberg H. , Nielsen L. S. , Klausen J. , Dahlén M. , Kristensen M. , Bisgaard M. L. , Møller N. , Mohr J.
Published: July 2010

Serum cholinesterase 2 (CHE2) was examined in a Danish material of normal families that has been tested earlier for 70–78 classical marker systems and 25 RFLP systems. DNA for RFLP typing was provided by transforming 16‐year‐old frozen lymphocytes. The frequency of allele CHE2*C5 + in the Danish population was found to be 0.0430. The highest lod score was between CHE2 and the γ‐crystallin gene cluster (CRYG) (ẑ= 4.21 at θ= 0.00 in females). The scores were from a single family with 15 children. CHE2 may, accordingly, be assigned to the location of CRYG: chromosome 2, bands q33‐q35.
Radial ray defects and associated anomalies
Authors: Cox H. , Viljoen D. , Versfeld G. , Beighton P.
Published: July 2010

In a series of 34 patients with defects of the radial ray, 24 individuals had additional clinical manifestations. A firm syndromic diagnosis could be reached in 17 persons (TAR syndrome 4, Holt‐Oram syndrome 8, Fanconi anaemia 2, VATER association 2, Radial ray‐choanal atresia 1). In the remainder, no specific diagnosis could be established. The heterogeneity of radial ray syndromes has important implications for prognostication and genetic counselling.
X‐linked olivopontocerebellar atrophy
Authors: Lutz R. , Bodensteiner J. , Schaffer B. , Gay C.
Published: July 2010

We present a kindred with a relatively pure cerebellar degeneration that demonstrates X‐linked recessive inheritance. The unique clinical picture of affected patients in our kindred is characterized by an infantile onset of ataxia; very slow rate of progression; normal strength, reflexes, and sensation; and cerebellar degeneration with involvement of the olive and pons demonstrated by neuroimaging techniques. The distinction between this and other reported olivopontocerebellar degenerations is made on the basis of the clinical features and mode of inheritance. It is not clear if the distinct clinical pattern in this kindred represents variable expression of a previously reported condition, allelic variance of previously reported kindreds, or a separate clinical entity. Molecular analysis, currently underway, may help settle the issue.
Parental origin of chromosomal non‐disjunction in a 49,XXXXY male using recombinant‐DNA techniques
Authors: Villamar M. , Benitez J. , Fernández E. , Ayuso C. , Ramos C.
Published: July 2010

We have analyzed the origin, in a patient with 49,XXXXY, of the four X‐chromosomes by means of recombinant DNA techniques. We found a maternal origin of the four X‐chromosomes due to non‐disjunctions in the first and second meiotic divisions.
Mental illness and cognition in relation to age at puberty: a hypothesis
Authors: Saugstad Letten F.
Published: July 2010

Onset of puberty is usually considered to coincide with the last major step in brain development: the elimination of some 40% of neuronal synapses. Mean pubertal age has declined by some 4 years during the last 100 years. There is a relation between age at puberty and body build, and between body build and mental illness. The difference in body build between schizophrenia (S) and manic‐depressive psychosis (MDP) is similar to that between late and early maturers. It is suggested that S affects late‐maturing individuals and MDP very early maturers. The observed marked rise in MDP and decline in the most malignant forms of S (non‐paranoid) are in agreement with MDP and S as neurodevelopmental disorders occurring at the extremes of maturation. Maturational irregularities are most likely to occur at the extremes, and it is suggested that abbreviation of the regressive process may have led to persistent redundancy of neuronal synapses in MDP and that prolongation of the process past the optimal has yielded an inadequate synaptic density in S. The lack of cerebral abnormality in the majority of MDP and the presence of only subtle structural deficits in S, are in agreement with this. The two disorders are probably as old as mankind, and early puberty is the necessary factor for the development of MDP and late puberty is the necessary factor for that of S. There is an inverse relation between spatial ability and rate of maturation, whereas verbal ability is unaffected by maturational rate. From a previous predominance in both sexes, spatial ability (Performance IQ scores) has been reduced to below verbal ability (Verbal IQ scores) in the female sex and in early maturing males.
Unusual cytogenetic mosaicism involving chromosome 14 abnormalities in a child with an MR/MCA syndrome and abnormal pigmentation
Authors: Cantú Eduardo S. , Thomas Ioan T. , Frias Jaime L.
Published: July 2010

An 8‐year‐old female child with mental retardation (MR), multiple congenital anomalies (MCA) and irregular pigmentation was shown to have karyotypic mosaicism involving chromosome 14 abnormalities. Four cell lines were found in both peripheral blood lymphocytes and skin fibroblasts and were represented by: a normal karyotype, an isopseudodicentric 14q [iso psu dic(14)], a ring 14 [r(14)], and a monosomy 14 [mono(14)]. Our results are compared with reported cases involving multiple abnormalities of specific chromosomes. Karyotypic mosaicism of comparable chromosome 14 abnormalities is rare, with only one known previous case. Detailed analysis of karyotypic mosaicism of rare chromosomal abnormalities is essential to determine meaningful correlations with specific patterns of malformation.
Two rare cases of 6p partial deletion
Authors: Jalal S. M. , Macias Vincent R. , Roop Heidi , Morgan Franciel , King Patricia
Published: July 2010

Two rare cases of 6p partial deletion (6p23 →pter) are described. Both patients are at or past the adolescent stage, with severe mental retardation and severe to moderate developmental retardation. Physical dysmorphic features that stand out are: short forehead, borderline microcephaly, low‐set malformed ears, hyperplastic nares, dental anomalies and short terminal phalanges. The diversity of the phenotypic features has considerable variations in patients with ring of 6, apparently reflecting the relative loss of p and q arms. A case of a larger terminal deletion and a report of an interstitial deletion is also reviewed.
Probability and likelihood in genetic counselling
Authors: Edwards A. W. F.
Published: July 2010

The aim of this paper is to clarify some of the concepts used in the calculation of risk in genetic counselling. The use of probability as a measure of risk in a particular case is reviewed, with special reference to the Fisher ‐ Neyman controversy. The technical concept of likelihood is then introduced and applied to risk probabilities themselves. The difficulties of interpretation are discussed, with a distinction drawn between calculating the risk for a child and inferring the genotype of his mother, even though the risk is wholly determined by the genotype. Fiducial inference is briefly mentioned, and the paper ends with a discussion of the problem which arises when the functional relationship between an unknown parameter and the unknown risk is not 1:1. The conclusion is tentatively reached that risk can only be gauged by probability and thus that prior probabilities must sometimes be assumed, but the paper is primarily intended as a guide and catalyst for the informed discussion of some of the difficulties, which may involve ethical dilemmas.
Evidence for non‐lysosomal storage of N‐acetylneuraminic acid (sialic acid) in sialuria fibroblasts
Authors: Thomas George H. , Scocca Jane , Miller Carol S. , Reynolds Linda
Published: July 2010

The results of the investigations reported here indicate that patients affected with the infantile sialic acid storage disorder (ISSD) and the original French sialuria patient suffer from distinct and fundamentally different disorders. While phase microscopy and immunochcmical studies demonstrated abnormal storage within intracellular inclusions in ISSD cells, no morphological evidence of storage within any subcellular organelles was found in the sialuria cells. Moreover, comparative subcellular fractionation studies on gradients of colloidal silica showed the excess sialic acid in ISSD cells to be located within the light (buoyant) lysosomal fraction, while the excessive, free sialic acid in the sialuria cells was found in the cytoplasmic fraction with no increased storage within the lysosomal tractions. It is concluded that the sialic acid abnormalities in ISSD and the French type of sialuria are the result of very different biochemical and genetically unrelated abnormalities.
Case of cyclopia with an unbalanced karyotype attributable to a balanced 3/7 translocation
Authors: Bürrig K. F. , Gebauer J. , Terinde R. , Pfttzer P.
Published: July 2010

This report presents a case of cyclopia attributable to an unbalanced karyotype in a family with a balanced, reciprocal 3/7 translocation. This case was the fifth recorded in three generations of this family. From this report it is possible that the simultaneous action of partial trisomy 3p and partial monosomy 7q may be one cause of holoprosencephaly.
Impact of medical genetics concerning phenylketonuria: accomplishments, status and practical future possibilities
Authors: Güttler Flemming
Published: July 2010

Millions of newborn infants are screened for phenylketonuria (PKU) to prevent the inherited metabolic error by dietary treatment. For some PKU patients a relaxed low‐phenylalanine diet will be lifelong. PKU‐women must return to a strict low‐phenylalanine diet before conception and during pregnancy to insure the delivery of a normal child. Two mutations that account for 60% of the PKU genes in Denmark are established and oligonucleotide probing enables carrier detection and genetic counselling. Primary hepatocytes can be successfully cultured and transformed with phenylalanine hydroxylase cDNA and somatic gene therapy of PKU may be a future possibility.
Albinism and skin cancer in Southern Africa
Authors: Kromberg Jennifer G. R. , Castle David , Zwane Esther M. , Jenkins Trefor
Published: July 2010

The presence of skin cancer was investigated in 111 albinos belonging to the black (Negro) population of Johannesburg, South Africa. The overall rate was 23.4%, the risk increasing with age. Identifiable risk factors included: environmental exposure to ultraviolet radiation; inability to produce ephelides (‘freckles’); and possibly ethnicity. The head was the site most commonly affected, and squamous was far more common than basal cell carcinoma. No melanomas were detected. Recommendations are made regarding prevention of skin cancer in the at‐risk group.
Hereditary spastic diplegia with mental retardation in two young siblings
Authors: Gustavson K.‐H. , Modrzewska K. , Erikson A.
Published: July 2010

Two young siblings with hereditary spastic diplegia and mental retardation (Böök's syndrome) have had detailed clinical investigations since infancy. The inheritance pattern of this syndrome in the present family fits well with an autosomal recessive trait ‐ with affected sibs of opposite sex, born to consanguineous healthy parents.
Achalasia microcephaly syndrome in a patient with consanguineous parents: support for a.m. being a distinct autosomal recessive condition
Authors: Hernández Alejandro , Reynoso Martha Celina , Soto Fernando , Quiñones David , Nazará Zamira , Fragoso Ruben
Published: July 2010

A 4 9/12‐year‐old boy with achalasia microcephaly syndrome (AMS), born to a consanguineous couple, is reported. Comparative analysis of this case and the patients previously described in a Mexican family supports the notion that the syndrome is a distinct autosomal recessive condition. It is interesting that the area of origin and ethnicity of both the present and the previously reported cases is northwest Mexico.
Multipoint linkage mapping of the Xq25‐q26 region in a family affected by the X‐linked lymphoproliferative syndrome
Authors: Sylla Bakary S. , Wang Qing , Hayoz Daniel , Lathrop G. Mark , Lenoir Gilbert M.
Published: July 2010

We have performed, in a large Swiss family, a study of linkage between various DNA markers in the Xq24–27 region and the locus for the X‐linked lymphoproliferative syndrome (XLP). Our results indicated that the marker DXS37 in Xq25‐q26 is genetically linked to the XLP syndrome. The multipoint linkage analysis showed that the disease locus is distal to DXS11, but proximal to the hypoxanthine phosphoribosyl‐transferase gene (HPRT).