bluuebunny/crossref_metadata_2025 huggingface dataset:
A new lethal chondrodysplasia with spondylocostal dysostosis, multiple internal anomalies and Dandy‐Walker cyst
Authors: Moerman Ph. , Vandenberghe K. , Fryns J. P. , Haspeslagh M. , Lauweryns J. M.
Published: July 2010

We describe here a female infant, exhibiting lethal short‐limbed dwarfism. The condition superficially resembled achondrogenesis. However, unlike achondrogenesis there was an associated severe spondylocostal dysostosis and major non‐skeletal anomalies, particularly a cerebellar Dandy‐Walker cyst, cardiovascular and urogenital malformations. The chondro‐osseous morphology was nonspecific. The case is believed to be unique. It is therefore suggested that this constellation of anomalies constitutes a “new” lethal syndrome, different from the delineated chondrodysplasias.
Cystic fibrosis; hint of linkage with F13B
Authors: Eiberg H. , Schmiegelow K. , Koch C. , Mohr J. , Schwartz M. , Niebuhr E.
Published: July 2010

In a material of 22 Danish families with cystic fibrosis we found a lod score of +1.71 at theta 0.05 for the CF‐F13B relationship.
Prenatal diagnosis of trisomy 20 mosaicism indicating esophageal and rectal origin
Authors: Vejerslev L. O. , Børlum K. G. , Jensen N. K. , Mikkelsen M.
Published: July 2010

Trisomy 20 mosaicism in cultured amniotic fluid cells has in only a few cases been confirmed in fetal tissue. This may lead to the assumption that the trisomic cells are of extra‐fetal origin and interruption of the pregnancy is not advisable. Chromosome analysis of numerous fetal tissues indicated in two cases the presence of one or more trisomy 20 cell clones in rectum and esophagus, respectively. The clinical significance of trisomy 20 mosaicism in single organs remains to be elucidated. Besides the karyotype, genetic counselling should take into account all accessible information of the pregnancy, e.g. ultra‐sound, serum alpha‐fetoprotein values and obstetrical history.
Glycosphingolipid studies of visceral tissues and brain from type 1 Gaucher disease variants
Authors: Nilsson Olle , Grabowski Gregory A. , Ludman Mark D. , Desnick Robert J. , Svennerholm Lars
Published: July 2010

Glucosylceramide and glucosylsphingosine isolated from spleen, liver and brain were quantitated and characterized in two unrelated patients with Gaucher disease, neither of whom had clinical or neuropathologic evidence of neuronal involvement. Visceral glucosylceramide accumulation did not differ in the two patients. Hepatic glucosylsphingosine content was 2‐fold greater in a young severely affected 3‐year‐old American Black patient compared to that in a 56‐year‐old Ashkenazi Jewish patient. In contrast, significant differences in glycosphingolipid content and composition were observed in the brains of these two cases. Cerebral and cerebellar cortical glucosylceramide accumulated to a greater extent (3‐fold) in the severely affected 3‐year‐old patient compared to that in the older case. The compositions of the acyl and sphingosyl base residues of glucosylceramide in the cerebral and cerebellar cortices from the Ashkenazi Jewish patient were similar to those in normal individuals. In comparison, the gray matter glucosylceramide in the severely affected patient had increased percentages of stearic acid (18:0) and eicosasphingenine (d20:1), suggesting that the accumulated substrate was derived from the brain ganglioside pool. Glucosylsphingosine was found in large amounts only in cerebral and cerebellar cortices from the severely affected patient. The glycolipid content and composition in this patient was similar to that found in the Norrbottnian (Type 3) form of Gaucher disease. The differences in glucosylceramide acyl and sphingosyl base composition in gray matter from the severely affected patient and that in the Ashkenazi Jewish patient suggested that the accumulated substrates were metabolized differently by the residual enzymes in each case. Since both glucosylceramide and glucosylsphingosine are substrates of the normal enzyme, the data suggested that the allelic mutations of acid β‐glucosidase can differentially alter the catabolism of these substrates and result in the different phenotypes of Gaucher disease.
Increased frequency of the apolipoprotein E‐4 isoform in male subjects with multifactorial hypercholesterolemia
Authors: Leren Trond P. , Bbøresen Anne‐Lise , Berg Kåre , Hjermann Ingvar , Luren Paul
Published: July 2010

The apoE polymorphism was studied by two‐dimensional gel electrophoresis in serum samples from 62 male subjects with multifactorial hypercholesterolemia and from 63 normal subjects. The apoE‐4 isoform was significantly more frequent (p<0.02) among the hypercholesterolemic subjects than among the normocholesterolemic controls.
Consanguinity among the Kuwaiti population
Authors: Al‐Awadi S. A. , Moussa M. A. , Naghuib K. K. , Farag T. I. , Teebi A. S. , El‐Khalifa M. , El‐Dossary L.
Published: July 2010

A total of 5,007 Kuwaitis were ascertained to study the incidence of consanguineous marriages during 1983. The rate of consanguineous mating was found to be 54.3% with estimated population incidence rates 52.9 to 55.7%. First cousin marriages were the most frequent type. The average inbreeding coefficient was 0.0219 which could be considered high.
Partial trisomy 12q: clinical and cytogenetic observations
Authors: Tengström C. , Wilska M. , Kähkönen M. , Autio S. , Leisti J.
Published: July 2010

High resolution chromosome banding showed a male infant with profound mental retardation, hypertonia and multiple congenital anomalies to have the karyotype 46, XY,‐ der(2), t(2;12)(q37.3;q24.13)pat. Most of the clinical findings were compatible with those of the previously described cases with partial trisomy 12q. Some of the clinical features seem to disappear with increasing age.
A new banding pattern of human chromosomes by in situ nick translation using ECO RI and biotin‐dUTP
Authors: Bullerdiek Jörn , Dittmer Jürgen , Faehre Angelika , Bartnitzke Sabine , Kasche Volker , Schloot Werner
Published: July 2010

Here we present first results of an attempt to replace the nicking activity of DNAase I by ECO RI for in situ nick translation of human chromosomes. For the detection of nick translated sites we used biotinylated dUTP. The procedure resulted in a distinct banding pattern of the chromosomes which does not seem to correspond to that reached by any known banding technique.
Direct and maternal aspects of the risk of cataract with partial disorders of galactose metabolism
Authors: Winder A. F. , Fielder A. R. , Mount J. N. , Menzies J. S.
Published: July 2010

Partial deficiencies of the enzymes of galactose metabolism can be associated with cataract, both directly and through maternal effects during pregnancy on enzymatically normal children. However, the associations are modest, variable and not obviously expressing cause and effect. We have recorded ophthalmological and biochemical observations including oral galactose tolerance on families with established enzyme deficiencies and/or cataracts, including possible effects during pregnancy. With the partial disorders a simple relationship between the extent of biochemical abnormality and the risk of cataract is not apparent and the association may be substantially coincidental. Cataract is common, and the attractive possibility that expression is significantly due to heterozygous or lesser deficiency of the enzymes of galactose metabolism, amenable to early dietary control of children or mothers at risk, is on present evidence not well supported.
The size of prometaphase chromosome segments Tables using percentages of haploid autosome length (750 band stage
Authors: Daniel Art
Published: July 2010

Tables of prometaphase chromosome segment sizes (750 band stage) are presented in units of percentage of haploid autosome length designating the distances from interband borders to telomeres. The Tables utilize ISCN (1981) nomenclature.
A study of DNA polymorphisms around the human apolipoprotein Al gene in hyperlipidaemic and normal individuals
Authors: Kessling A. M. , Horsthemke B. , Humphries S. E.
Published: July 2010

We have used a 2.2 kb fragment of the human apolipoprotein AI (apo AI) gene to screen a number of unrelated individuals for common restriction fragment length polymorphisms (RFLPs) of the gene. As well as the previously reported SstI RFLP (allele frequencies in normolipidaemic individuals 0.94 and 0.06) we have detected RFLPs with the enzymes PstI and XmnI (allele frequencies in normolipidaemic individuals 0.88 and 0.12 for both polymorphisms). In the population studied, the RFLPs appear to be in linkage equilibrium and can be used in conjunction as a haplotype, with a PIC value (polymorphism information content) of 0.5. Significant differences in allele frequency were observed between subgroups of hyperlipidaemic patients and normolipidaemic controls. There is no strong population association in our patient group between any allele of the RFLPs studied and hypertriglyceridaemia.
A psychometric study of children at‐risk for Huntington disease
Authors: Catona Mark C. , Lazzarini Alice M. , McCormack Michael K.
Published: July 2010

Huntington disease (HD) is an autosomal dominant disorder of the central nervous system with an average age of onset between 35 and 45 years and symptoms progressing slowly over the next 10 to 20 years. Research in the past few years has focused on the hypothesis that a presymptomatic or prodromal phase for HD is detectable at least 10 years prior to chronic symptoms. This study attempts to identify possible signs of a prodromal phase for HD in children who are at primary (50%) and secondary (25%) risk for HD using a screening battery of psychometric tests. The children tested were between the ages of 5 1/2 and 15 years and the tests used were the WISC‐R, the PPVT‐R, and the VMI. Results from this study indicated performance on the WISC‐R Digit Span and to a lesser extent Coding subtests might be useful in assessing a possible memory dysfunction in children at‐risk for HD.
Norrie disease caused by a gene deletion allowing carrier detection and prenatal diagnosis
Authors: Chapelle Albert de La , Sankila Eeva‐Marja , Lindlöf Mikael , Aula Pertti , Norio Reuo
Published: July 2010

Carrier determination and prenatal diagnosis in Norrie disease (ND) has so far not been reported. We describe a kindred with 4 members affected by ND in which a deletion comprising gene locus DXS7 on the short arm of the X chromosome defined by probe L1.28 causes the disorder. This allowed us to predict via chorion villus biopsy that a male foetus of a carrier woman is unaffected.
Detection and interpretation of two different cell lines in triploid abortions
Authors: Uchida Irene A. , Freeman Viola C. P. , Chen Ping‐le
Published: July 2010

Among a series of 98 triploid abortions, there were four specimens with two cell lines. The detection of two clones was by Q‐banding of chromosomes. Two of these four specimens were dizygotic twins, the third was either a mosaic or monozygotic twins with loss of a sex chromosome from one twin and the fourth was best explained as a chimaera which arose by fertilization of two female pronuclei by three sperms. These two unusual specimens had XYY sex chromosome complements which is rare among triploids. Two additional specimens were diagnosed clinically as possible twin pregnancies but only one cell line was identified from tissue culture. The frequency of twins was of the order of 1/33.
Partial 8p trisomy due to interstitial duplication: karyotype: 46, XX, inv dup(8) (p21.1→p22)
Authors: Fryns J. P. , Kleczkowska A. , Dereymaker A. M. , Hoefnagels M. , Heremans G. , Marien J. , Berghe H. van den
Published: July 2010

A 24‐year‐old female with severe mental retardation, congenital malformations and dysmorphic features is described. 8p trisomy due to a de novo inv dup(8) (p21.1→p22) was found in her karyotype. Other published cases with 8p trisomy are reviewed.
Mental retardation with pterygia, shortness and distinct facial appearance A new MCA/MR syndrome
Authors: Haspeslagh M. , Fryns J. P. , Mûelenaere A. de , Schautteet L. , Eeckhoutte I. van , Berghe H. van den
Published: July 2010

During a systematic survey of the mentally retarded, 3 related females were seen with a similar syndrome of shortness, unusual combination of craniofacial anomalies (trigonocephaly; bulging forehead; flat face; posteriorly angulated, lowset ears and microretrognathia), and genital hypoplasia in all 3 cases, and multiple pterygia in one.

The facial changes were also noted in 2 grandmothers and may indicate autosomal dominant inheritance of this presently “private” MCA/MR syndrome.
An unusual case of X‐15 translocation: evidence for the presence of an ‘activator’ region on Xpter of Man
Authors: Crocker M. , Jonasson J. , Patel C.
Published: July 2010

A case of an X‐autosome rearrangement is presented in which part of the Xpter is deleted but the STS and MIC2X loci are retained. The normal X is late replicating in 97/100 lymphocytes and 50/50 fibroblasts examined. It is assumed that the initial X‐inactivation in the embryo is random, but that cells with the rearrranged X inactivated are selected against because inactivation spreads into the attached autosomal segment. This spreading, through the normally active STS locus, is hypothesised to be caused by deletion of a part of Xpter which is critical for the maintenance of activity of the Xpter region as a whole.
Genetic regulation of the kinetics of glucose‐induced insulin release in man Studies in families with diabetic and non‐diabetic probands
Authors: Iselius L. , Lindsten J. , Morton N. E. , Efendić S. , Cerasi E. , Haegermark A. , Luft R.
Published: July 2010

Insulin release and sensitivity were estimated from glucose and insulin curves obtained at a glucose infusion test performed on altogether 601 subjects belonging to 155 nuclear families. Ascertainment was through one of the parents, and 96 of the probands had diabetes with clinical onset after the age of 30 years, while 59 were healthy subjects. Three variables obtained by a computer model were analysed, i.e. the glucose regulation of insulin release by a direct stimulatory event (KI) and time‐dependent modulatory events (KP) as well as insulin sensitivity (KG). Complex segregation analysis revealed that the variables are genetically regulated, but there was no evidence for a major locus. The children of the diabetics did not differ from those of the non‐diabetics as far as insulin release is concerned.
Metacarpophalangeal pattern profile analysis in Prader‐Willi syndrome A follow‐up report on 38 cases
Authors: Butler Merlin G. , Meaney F. John
Published: July 2010

Metacarpophalangeal pattern profile (MCPP) was determined on 38 Prader‐Willi syndrome individuals and compared with a previous report on 16 patients. Chromosome analysis showed an interstitial deletion of the long arm of chromosome 15 in 20 subjects and normal chromosome results in the remaining 18 individuals. The mean hand profile of 38 individuals was essentially flat while the profiles for the two groups based on chromosome findings were separate in the metacarpal area. Correlation studies confirmed the homogeneity of the deletion group relative to Prader‐Willi syndrome individuals with normal chromosomes. Discriminant analysis of Prader‐Willi syndrome versus control individuals produced a function of three MCPP variables plus age which may be applied as another diagnostic tool.
Autosomal dominant cataract and microcornea associated with myopia in a Sicilian family
Authors: Mollica F. , Volti S. Li , Tomarchio S. , Gangi A. , Risiglione V. , Gorgone G.
Published: July 2010

A Sicilian family is reported in which 36 individuals, in 5 successive generations, were affected with congenital cataracts, microcornea and myopia with an autosomal pattern of inheritance.
Yq deletion (q11.21) in a H‐Y+ azoospermic male
Authors: Martín María José , Rodriguez María Teresa , Aller Vitalino , Abrisqueta José A. , Rojo José M.
Published: July 2010

A large deletion of the long arm (q11.21) of chromosome Y without mosaicism was found in a 28‐year‐old male. The proband has a normal height and normal male habitus but with azoospermia. The occurrence of H‐Y+ level, azoospermia and loss of a great portion of euchromatic Yq in the proband is analyzed.
Clinical, chromosomal and enzymatic studies in four cases of rearrangements of chromosome 7*
Authors: Baeteman M. A. , Philip N. , Mattei M. G. , Mattei J. F.
Published: July 2010

We report here four cases of unbalanced chromosomal rearrangements involving partial monosomies and trisomies of chromosome 7. The quantitative expression of diaphorase 2 (DIA‐2), beta‐glucuronidase (GUS‐β) and argino‐succinate‐lyase (ASL) were measured in these patients and compared with controls. The results suggest that the DIA‐2 locus is in the band 7p221→q21, the GUS‐β locus in the band 7p22<q21 and the ASL locus in the band 7p221<q22.
Congenital contractural arachnodactyly Report of four additional families and review of literature
Authors: Arroyo Maria A. Ramos , Weaver David D. , Beals Rodney K.
Published: July 2010

We report here four families with congenital contractural arachnodactyly (CCA) in which a wide range of phenotypic expression is observed. In one family with a large number of affected individuals the condition is mildly expressed. These individuals usually have crumpled ears, camptodactyly with ulnar deviation of the fingers, adducted thumbs, limited elbow and/or knee extension, and hypoplasia of the calf muscles. Arachnodactyly is not a constant feature. No spinal deformities are present and only the proband has clubfoot deformities. With time, affecteds have experienced spontaneous improvement of their contractures and their condition in adulthood has not interfered with a normal lifestyle. Within this family there is little phenotypic variation between affected individuals. Those affected within each of the other families have had varying degrees of severity of the condition. A review of 29 other kindreds described in the literature with congenital contractural arachnodactyly shows that in this condition the most common features are abnormally formed ears, camptodactyly, arachnodactyly, adducted thumbs, limited movement of the elbows and knees, and underdevelopment of the calf muscles. Spontaneous improvement of the contractures with age is reported in 94% of cases. Kyphosis, scoliosis or kyphoscoliosis occurred in 50% and these defects were present in those who where more severely affected with CCA. No ocular problems have been reported in this syndrome, but congenital heart defects have occurred in 14.7%. Marfan syndrome is the most important condition to differentiate from congenital contractural arachnodactyly since these two conditions are similar phenotypically. However, in the former there are frequently serious ocular and cardiovascular problems which lead to significant morbidity and/or early death.
Detection at amniocentesis of a maternally inherited X; Y translocation
Authors: Speevak M. , Clifford B. , Cox D. M. , Hunter A. G. W.
Published: July 2010

G banded chromosomal analysis of cells from a routine amniocentesis revealed a Y to X translocation in the fetus. The same unbalanced translocation was found in the mother who was disproportionately short. H‐Y antigen titers in the mother were intermediate and steroid sulfatase activity was in the normal female range. At birth the baby exhibited few dysmorphic features but appeared to have short limbs.
Multiple dysmorphic features and pancytopenia: a new syndrome?
Authors: Sackey Kwesi , Sakati Nadia , Aur Rhomes J. A. , Shebib Souheil , Sabbah Rajeh S. , Rifai Samira
Published: July 2010

Various degrees of bone marrow aplasia have been described in association with distinctive congenital anomalies such as the Fanconi Pancytopenia Syndrome (F.P.S.), Thrombocytopenia Absent Radii Syndrome (T.A.R. Syndrome) the Aase Syndrome and Diamond‐Blackfan Anemia. This case report describes a child with pancytopenia and several dysmorphic features which have never collectively been described in any of the bone marrow aplasia syndromes listed above. In this paper, we report a constellation of dysmorphic features and pancytopenia which may constitute a new syndrome.
A new syndrome: thrombocytopathia, muscle fatigue, asplenia, miosis, migraine, dyslexia and ichthyosis
Authors: Stormorken Helge , Sjaastad Ottar , Langslet Asbjørn , Sulg Ilmar , Egge Kjell , Diderichsen Jorgen
Published: July 2010

A new multifacetted syndrome inherited as an autosomal, dominant trait is described encompassing not only two hitherto undescribed hereditary defects ‐ thrombocytopathia and asplenia ‐ but also muscle contractile defect, migraine‐like headache, miosis, dyslexia and ichthyosis. None of these defects has so far been assigned to a specific chromosome or linkage group. Further studies on the various aspects of the syndrome are in progress.
Partial trisomy 6p and partial monosomy 9p from a de novo translocation 46, XY, ‐9, + DER(9)T(6:9)(p211:p24)
Authors: Eden Melanie S. , Thelin James W. , Michalski Karen , Mitchell Joyce A.
Published: July 2010

This report describes an adult male with a partial trisomy 6p(p211‐pter) and a partial monosomy 9p(9p24‐pter) resulting from a de novo unbalanced translocation. This patient does not show the classical features of the 9p partial monosomy syndrome, thus disputing the claim of Hoo et al. (1982) that 9p24 is the critical segment for the monosomy syndrome. Partial trisomy for 6p has only been previously reported in children. In addition to the chromosomal anomalies, the patient has autosomal recessive spinal muscular atrophy with a different age of onset than two affected sibs. Finally, he shows unusual audiologic and ophthalmologic signs not previously reported as part of the 9p monosomy or 6p trisomy syndromes.
Chromosomal abnormalities associated with congenital contractures (arthrogryposis)
Authors: Reed S. D. , Hall J. G. , Riccardi V. M. , Aylsworth A. , Timmons C.
Published: July 2010

In a study of 350 patients with multiple congenital contractures (arthrogryposis), 80 (23%) patients had mental retardation or were developmentally delayed. Out of that group of 80 patients, 13 (16%) were found to have abnormal karyotypes. Two of the thirteen had a family history of chromosomal abnormalities without congenital contractures, therefore, 11 patients had chromosomal anomalies which appeared to be associated with the congenital contractures. Five of the eleven (45%) had chromosome mosaicism, three of those had tissue mosaicism. Two had abnormal skin fibroblast cell lines and normal peripheral leukocyte chromosome studies and one had a normal bone marrow karyotype with abnormal peripheral leukocyte chromosome studies. Chromosome studies were done in these patients with congenital contractures because of developmental delay and multisystem involvement, or recognition of clinical features typical of a chromosomal syndrome. We recommend first lymphocyte; and if those are normal, then fibroblast studies be done on all patients with multiple joint contractures and developmental delay, particularly if unusual facial features or multisystem abnormalities are present.
Carrier detection in Becker muscular dystrophy using creatine kinase estimation and DNA analysis
Authors: Kingston H. M. , Sarfarazi M. , Newcombe R. G. , Willis N. , Harper P. S.
Published: July 2010

Serum creatine kinase levels in 39 control females and 59 obligate carriers of Becker muscular dystrophy (BMD) have been used to construct likelihood ratios for carrier detection. In 24 possible carriers of BMD, analysis of DNA with X chromosome specific DNA probes linked to the dystrophy gene, has been used in conjunction with creatine kinase measurement to calculate final risk estimates of carrier status. Incorporation of information from probe genotype into the Bayesian calculation, enables a substantially lower risk to be deliniated for some possible carriers of the BMD gene. Thus, although the existing DNA probes are not sufficiently closely linked to BMD to be used in prenatal diagnosis, they can make a major contribution to genetic counselling by refining the estimated probability of carrier status.
Evaluation of urinary cells in acid cholesteryl ester hydrolase deficiency
Authors: Chatterjee Subroto , Castiglione Elisabeth , Kwiterovich Peter O. , Hoeg Jeffrey M. , Brewer H. Bryan
Published: July 2010

Deficiency in the lysosomal enzyme responsible for cholesteryl ester hydrolysis, acid cholesteryl ester hydrolase (E.C. 3.1.1.13), leads to two clinically recognized diseases: Wolman disease and cholesteryl ester storage disease (CESD). The enzyme defect in these diseases has been detected in all the tissues studied including leukocytes, fibroblasts and liver. Analysis of urinary sediment from well characterized cases of Wolman disease and CESD also revealed the shedding of lipid enriched renal tubular cells. Morphologic, enzymic and lipid compositional studies of these cells indicate that the enzyme deficiency observed in fibroblasts and leukocytes from these individuals are reflected in these cells shed in the urine. These findings in renal tubular cells confirm and extend those made in other cell types. These studies indicate that analysis of urinary sediment in suspected cases of acid cholesteryl ester deficiency may provide a meaningful approach for monitoring therapeutic attempts involving enzyme infusion and gene therapy.
Unspecific reactions of HLA‐B antisera on fibroblasts from patients and carriers of Duchenne muscular dystrophy
Authors: Kirbach E. D. Aragon de , Willers I. , Singh S. , Goedde H. W.
Published: July 2010

Skin fibroblasts of patients with Duchenne muscular dystrophy were analysed for HLA tissue antigens. For the examination of the antigens two modified methods were used: the microdro‐plet cytotoxicity assay on fibroblast suspension and the cytotoxicity assay on fibroblast monolayer cultures using fTuorochromasia. The HLA determination on the fibroblast suspensions of the patients showed a variety of unspecific HLA expressions which were not found in fibroblasts of healthy controls. These reactions were not apparent in the test in monolayer cultures. The exact cause has not been elucidated yet, but it appears to have a strong relation to some membrane abnormality in cells of DMD patients. The reproducible lack of unspecific reactions on monolayer cultures lead us to propose that these expressions arise from artificial injuries to membranes of these patient cells during trypsination or centrifugation. The validity of this test has been confirmed by a blind study.
Prometaphase chromosome analysis as a routine diagnostic technique
Authors: Barnes Islay C. S. , Maltby Edna L.
Published: July 2010

The use of techniques for the production of prometaphase chromosomes leading to increased resolution of banding patterns has resulted in problems as well as advantages in their routine use. A simple technique utilising the folate antagonist methotrexate has been in use in this regional diagnostic cytogenetics centre for three years, and a number of chromosome abnormalities have been detected in cases previously reported as normal following G banding studies. With reference to this, the routine analysis of prometaphase‐type chromosomes is discussed and assessed.
Accumulation and defective β‐oxidation of very long chain fatty acids in Zellweger's syndrome, adrenoleukodystrophy and Refsum's disease variants
Authors: Poulos A. , Singh H. , Paton B. , Sharp P. , Derwas N.
Published: July 2010

The accumulation of very long chain fatty acids in plasma and skin fibroblasts was measured in at least four separate inherited disease states. Both the magnitude and the nature of the fatty acid changes reflected the clinical status of individual patients. In Zellweger's syndrome, and to a lesser extent in infantile Refum's disease, there was an increase in 24:0, 26:0, 26:1, and a number of even longer chain fatty acids, while in the X‐linked form of adrenoleukodystrophy these changes were less pronounced.

Zellweger fibroblasts in culture took up lignoceric, phytanic and stearic acids and incorporated them into a variety of lipids in a manner comparable to control fibroblasts. However, these cells were unable to convert phytanic or lignoceric acid to CO2. Infantile Refsum's and X‐linked adrenoleukodystrophy fibroblasts showed normal conversion of these acids to CO2. Normal fibroblast homogenates produced radioactive acetate from [1‐14C] stearic and [1‐14C] lignoceric acids indicating that both substrates were β‐oxidised under these conditions. Homogenates of fibroblasts from all patients with biochemical evidence of accumulation of very long chain fatty acids showed normal or near‐normal stearic acid β‐oxidation, but were deficient in lignoceric acid β‐oxidation. Residual lignoceric acid β‐oxidation activity varied from approximately 15% in Zellweger syndrome up to 50% in X‐linked adrenoleukodystrophy.

It is postulated that the accumulation of very long chain fatty acids results from defects in peroxisomal β‐oxidation. In Zellweger's syndrome, and possibly in infantile Refsum's disease, it is probable that this defect is secondary to a primary abnormality affecting the structure and/or function of peroxisomes, while the primary defect in X‐linked adrenoleukodystrophy may be confined to a pathway specific for the oxidation of very long chain fatty acids.
Cryptophthalmos ‐ syndactyly syndrome without cryptophthalmos
Authors: Koenig R. , Spranger J.
Published: July 2010

Based on a personal observation and a review of the literature five cases with the so‐called cryptophthalmos‐syndactyly syndrome but without cryptophthalmos are presented. It appears that eye lesions are non‐obligatory components of a pleomorphic condition which may be overlooked in the absence of the name‐giving anomaly. The diagnosis of the cryptophthalmos‐syndactyly syndrome must be considered in patients with a combination of acrofacial and urogenital malformations with or without cryptophthalmos.
Infantile type of sialic acid storage disease with sialuria
Authors: Paschke E. , Trinkl G. , Erwa W. , Pavelka M. , Mutz I. , Roscher A.
Published: July 2010

We describe a male infant of Austrian ancestry, the main clinical features including attacks of dyspnea due to laryngomalacia, severe mental and motor retardation, pronounced splenohepa‐tomegaly and vacuolisation of peripheral lymphocytes. The clinical condition deteriorated progressively and the child died at the age of 21 months.

Phase and electron microscopy of cultured skin fibroblasts showed multiple vacuoles and inclusions suggestive of a lysosomal storage disorder.

Increased excretion of free sialic acid was demonstrated by resorcinol staining after routine thin‐layer screening for urinary oligosaccharides. Quantitative analyses of urine, leucocytes and cultured fibroblasts revealed 10 to 30‐fold increased concentrations of free sialic acid. In addition, 3‐fold elevated amounts of sialyloligosaccharides were found in the urine. The activities of a variety of lysosomal enzymes, including sialidase, were normal.

Our case is compared with infantile sialic acid storage disease recently observed by other authors. The close convergence of clinical, morphological and biochemical signs support the concept of a distinct lysosomal disease entity. The basic defect is so far unknown.
Detection and exclusion of carriers of ornithine transcarbamylase deficiency by RFLP analysis
Authors: Schwartz M. , Christensen Ernst , Christensen Niels C. , Skovby Flemming , Davies Kay E. , Old John M.
Published: July 2010

By examining a restriction fragment length polymorphism (RFLP) detected by a gene specific DNA probe of ornithine transcarbamylase (OTC), we have been able to follow the segregation of the defective gene in a family with OTC deficiency. We have identified three sisters of the proband as carriers, and excluded a fourth as a carrier.
Reciprocal effects of apolipoprotein E alleles (ε2 AND ε4) on plasma lipid levels in normolipidemic subjects
Authors: Eto M. , Watanabe K. , Ishii K.
Published: July 2010

A significantly lower frequency of the ε2 allele and a significantly higher frequency of the ε3 allele were found in the normolipidemic Japanese population than those in the normolipidemic Caucasian populations. We have compared plasma lipid variables among the apolipoprotein (apo) E phenotype groups and estimated the average effects of the three common alleles (ε2, ε3 and ε4) on plasma lipid levels in normolipidemic subjects. Plasma triglyceride (TG), very low density lipoprotein (VLDL)‐TG, VLDL‐cholesterol (C) and apo E levels were high in the apo E3/2 group, intermediate in the apo E3/3 group and low in the apo E4/3 group, whereas plasma total cholesterol (TC), low density lipoprotein (LDL)‐C and high density lipoprotein (HDL)‐C levels were low in the apo E3/2 group, intermediate in the apo E3/3 group and high in the apo E4/3 group. Furthermore, the ε2 allele had an effect to increase the TG, VLDL‐TG, VLDL‐C and apo E levels and decrease the TC, LDL‐C and HDL‐C levels, whereas the ε4 allele had an effect opposite to the el allele. These results indicate that the ε2 and ε4 alleles have the reciprocal effects on plasma lipid, lipoprotein and apo E levels.
The Grant Syndrome: Persistent Wormian bones, blue sclerae, mandibular hypoplasia, shallow glenoid fossae and campomelia ‐ an autosomal dominant trait
Authors: Maclean J. Robert , Lowry R. Brian , Wood Betty J.
Published: July 2010

A father and daughter with apparently unique clinical findings are described. The findings include persistent Wormian bones, blue sclerae, mandibular hypoplasia, shallow glenoid fossae and campomelia. Apparently it is an autosomal dominant trait. Although the disorder is in the osteogenesis imperfecta group, nevertheless it appears to be different and until the basic defect is found we have named it “The Grant Syndrome”.
A family with craniofrontonasal dysplasia, and fragile site 12q13 segregating independently
Authors: Kumar D. , Clark J. W. , Blank C. E. , Patton M. A.
Published: July 2010

Coronal craniosynostosis, hypertelorism, telecanthus, broad grooved nasal tip, dental anomalies, mild syndactyly and broad thumbs, consistent with craniofrontonasal dysplasia are described in a family of four affected females over three generations. Documentation of the family is of interest because of variable clinical features and an excess of affected females. The excess of females observed in this condition is as yet unexplained, but cannot be referred simply to X‐linked dominance with lethality in the male. Autosomal dominance with less frequent and less severe expression in the male is more tenable. Chromosome analysis on two affected family members revealed a fragile site at 12q13, which was also found in a phenotypically normal family member. A third affected individual did not exhibit this fragile site. Thus it appears that there is a heritable fragile 12q13 site segregating in this family separately from the gene for craniofrontonasal dysplasia.
Adult polycystic liver and kidney diseases are separate entities
Authors: Karhunen PekkaJ. , Tenhu Martti
Published: July 2010

In 22 cases of either adult polycystic liver (PLD) or polycystic kidney (APCD) disease, considered as one dominantly inherited entity, both diseases occurred together only once. Early microscopical cystic lesions that are typical of PLD were found in another case of APCD. In this medicolegal autopsy series the incidence of PLD was 0.05% and that of APCD 0.08%.

Cerebral haemorrhage or cerebral aneurysms were found in 50% of APCD cases but in none of the cases with only PLD (p<0.01). Of the cases with PLD, 50% had associated renal cysts and 10% of the cases with APCD had associated liver cysts. The same medicolegal autopsy material yielded a prospective series of 95 male cases, where, however, kidney cysts were normally present in over 50% and liver cysts in about 20% of the cases of similar age. Thus, a part of the association between cystic disease of the liver and kidney may have been based on the common occurrence of cysts in old age.

V. Meyenburg's complex was the microscopic alteration associated with cysts in PLD. It was associated as well with liver cysts in APCD suggesting that an intricate relation between PLD and APCD does occur in part of the cases, in this series characterized by large size APCD kidneys.

The results indicate that in adults PLD is an entity of its own, expressed in most of the cases independently of APCD.
Relative reliability of three different discriminant analysis methods for detecting PKU gene carriers
Authors: Wenger S. L. , Vieira P. W. , Breck J. M. , Steele M. W.
Published: July 2010

A previously derived discriminant function for detecting classical PKU gene carriers without a priori pedigree probability was reevaluated using a large sample size. The test involves fluorometric measurement of fasting phenylalanine and tyrosine plasma levels. Among 75 controls and 45 known carriers, 95% could be classified as to their carrier status with greater than 98% accuracy. The accuracy of our method in classifying our population compared favorably to that of two other discriminant analysis methods requiring a priori probability.
Partial trisomy 3p syndrome
Authors: Reiss JacobA. , Sheffield LesJ. , Sutherland GrantR.
Published: July 2010

Two cousins with an unbalanced chromosome translocation (partial trisomy 3p) are described. Both children have a clinically recognizable syndrome of square facies with prominent cheeks, narrow bitemporal regions, psychomotor retardation and congential heart disease. Extended family studies showed one other individual proven to have partial trisomy 3p karyotype, two retarded individuals with congenital heart disease who probably had it, and 14 balanced carriers of the translocation t(l;3)(q43;p21).

This report confirms the characteristic clinical appearance of affected individuals and emphasizes the frequency in which congenital heart disease is the presenting feature of partial trisomy 3p. An additional 22 cases of partial 3p trisomy are reviewed.
Normal female carrier and affected male half‐sibs with t (X;5) (q13;p15)
Authors: Callen D. F. , Sutherland G. R.
Published: July 2010

A unique family in which half‐brothers have a maternally derived t(X;5) (q13;p15) and similar genital malformations is described. This family provides evidence for a gene required for male genital development located at Xq13.
Comments on methods and results in: Sherman et al., “Segregation analysis of balanced pericentric inversions in pedigree data”
Authors: Stene Jon
Published: July 2010

The analysis by Sherman et al. (1986), its basis and results have been examined. The analysis relies on general methods, which may give acceptable results under the special conditions considered by the authors, but will usually produce more or less misleading results. The program POINTER (Lalouel & Morton 1981) is shown to be based partly on a chain of irrelevant arguments for the actual context. The so‐called “conventional ascertainment rules” (Morton et al. 1983) are shown to produce misleading results in cases where their assumptions are not satisfied. The mean risk for unbalanced offspring is underestimated because of an erroneous ascertainment correction. The segregation frequencies are found to be different in three national samples, contrary to the claim by Sherman et al. Only a small proportion of all information available in the data has been utilized. Alternative and more appropriate models, hypotheses and procedures have been suggested. The frequent use of packages with computer programmes of standard statistical procedures in nonstandard situations with data from collaborative studies in human cytogenetics is discussed.
Heterochromatinization of human X‐ chromosomes: classification of replication profile
Authors: Babu A. , Chemitiganti S. , Verma R. S.
Published: July 2010

The replication profiles of human X‐chromosomes are studied by RBA‐technique. It is suggested that the late replicating X‐chromosome can be arbitrarily classified into 8 types. Furthermore, data suggest that the individual cells are under self‐control pertaining to the inactivated X‐chromosome. This may reflect that the altered chromatin may not be uniform in the process of inactivation.
Autosomal dominant lamellar ichthyosis
Authors: Toribio J. , Redondo V. Fernandez , Peteiro C. , Zulaica A. , Fabeiro J. M.
Published: July 2010

Five members of two generations of one family were affected with lamellar ichthyosis, suggesting autosomal dominant transmission. The clinical and histopathological characteristics of the cases described here are similar to those reported by Traupe et al. (1984) as autosomal dominant lamellar ichthyosis and thus confirm the existence of this new form of ichthyosis.
Peculiar face, deafness, cleft palate, male pseudohermaphroditism, and growth and psychomotor retardation; a new autosomal recessive syndrome?
Authors: Ieshima Atsushi , Koeda Tatsuya , Inagaki Masumi
Published: July 2010

Two siblings with peculiar facies, deafness, cleft palate, male pseudohermaphroditism, and growth and psychomotor retardation were reported. The similarity of both the dysmorphic features and the clinical course suggests a new syndrome, which inheritance is considered to be autosomal recessive.
Dermatoglyphics in Congenital Adrenal Hyperplasia (CAH)
Authors: Börger Doris , Held Karsten R. , Lüttgen Sabine
Published: July 2010

Dermatoglyphic findings were compared in 42 patients (32 females, 10 males) with Congenital Adrenal Hyperplasia (CAH) and 110 normal controls (70 females, 40 males). In CAH males, an excess of whorls (p < 0.001), an increased total finger ridge count (p < 0.05), and an increased frequency of patterns in the fourth interdigital area (p < 0.025) was found. A main line A terminating high in the hypothenar area (p < 0.05), and a missing c‐triradius or an abortive main line C (p < 0.05) was observed in CAH females. Both sexes displayed an increase in the frequency of small radially directed hypothenar patterns (p < 0.05) and Sydney lines (p < 0.01).
Pepsinogen A polymorphism in gastric mucosa and urine, with special reference to patients with gastric cancer
Authors: Westerveld B. D. , Pals G. , Defize J. , Pronk J. C. , Frants R. R. , Ooms E. C. M. , Kreuning J. , Eriksson A. W. , Meuwissen S. G. M.
Published: July 2010

Electrophoretic pepsinogen A patterns were determined in gastric fundic mucosa biopsies from 601 patients with various gastric disorders and 25 healthy volunteers. Pepsinogen A patterns with an intense fraction 5 appeared to be associated with gastric cancer and premalignant changes of the stomach (p < 10‐9). In 60 individuals pepsinogen A patterns were determined in normal mucosa from different parts of the stomach. No differences were found between these patterns. In 29 out of 59 gastric cancer patients pepsinogen A could be demonstrated in the macroscopically malignant tissue. In two cases a different pattern compared with uninvolved fundic mucosa was observed.

During a follow up study, major changes in the pepsinogen A pattern were observed in 7 out of 56 patients. In 8.6% of the examined patients urinary pepsinogen A patterns differed considerably as compared with the pattern observed in the gastric fundus.

The results suggest that the highly significant association between intense Pg5 (the product of the D gene) and gastric cancer or its precursors may be caused by genetic as well as non‐genetic factors.
A recent survey of consanguineous marriages in Japan
Authors: Imaizumi Yoko
Published: July 2010

A survey of consanguineous marriages in Japan was conducted on September 1 in 1983 through questionnaires. The total number of couples studied was 9,225 chosen from six widely different areas of Japan. The rates of first cousin marriages and of total consanguineous marriages for all areas are 1.6% and 3.9%, respectively. The mean inbreeding coeffient is 0.00134 for all areas of Japan. On the other hand, the rate of total consanguineous marriages was ten times higher in Fukue‐Shi (7.9%) than in Asahikawa city area (0.78%). The rate of total consanguineous marriages is decreased with the marriage year in Japan, where the rate of first cousin marriages has changed remarkably.
High‐resolution cytogenetic studies in patients with Prader‐Willi syndrome
Authors: Takano Takako , Nakagome Yasuo , Nagafuchi Shigeo , Tanaka Fumihiko , Nakamura Yasuhide , Nagano Tetsu , Tanae Ayako , Hibi Itsuro
Published: July 2010

We investigated 24 patients with Prader‐Willi syndrome by the high‐resolution banding technique. Their history and clinical findings were also examined in some detail.

Twelve had interstitial deletion of 15q;.del(15) (ql 1.2q13) in 11 cases and del(15) (ql 1.2q12) in one case. Six revealed normal karyotypes at about 500–850 bands per haploid‐set level. In an additional six cases, no deletion was detected. However, we took the results as tentative, as the observed karyotypes were at the 400‐bands level. During the course of this study, it was realized that a small deletion in the proximal 15q could be easily overlooked when a mitotic spread around 400‐bands or less per haploid‐set level was used.

There was no distinct difference in the clinical features of patients with interstitial deletion and those with a normal karyotype. Two cases in the latter group lacked some of the typical features of the former group, e.g. poor fetal vigor, neonatal feeding difficulty, hypotonia, and delayed motor development.
Analysis of fragile X‐mental retardation families using flanking polymorphic DNA probes
Authors: Goonewardena P. , Gustavson K.‐H. , Holmgren G. , Tolun A. , Chotai J. , Johnsen E. , Pettersson U.
Published: July 2010

Fragile‐X mental retardation (FRAX‐MR) is one of the more common X‐linked disorders affecting 1 in 1,500 newborn males. This disease is characterized by the expression of fragile site in the region q27.3 of the X‐chromosome of affected boys when their lymphocytes are cultured in folate deficient medium. In most patients there is macroorchidismo postpubertallyo. The clinical diagnosis of carrier females based on the expression of fragile site in Xq27.3 is usually difficult and sometimes impossible. About half of the carrier females escape diagnosis by this method. Furthermore, prenatal diagnosis is not always feasible. Using Restriction Fragment Length Polymorphism (RFLP) and cloned DNA segments from the region Xq27‐Xqter as probes, we have investigated Swedish families with FRAX‐MR in three generations. Interesting observations, previously unreported to our knowledge, have been made in some patients and carrier mothers, using one of the probes which is localized to the distal end of Xq. The significance of these findings and the linkage of the disease locus to the different probes used in this study is presented.