bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal diagnosis of fragile X syndrome by direct detection of the dynamic mutation due to an unstable DNA sequence
Authors: Yamauchi Masatake , Nagata Shin , Seki Naohiko , Toyama Yoshiro , Harada Naoki , Niikawa Norio , Masuno Ichiro , Kajii Tadashi , Hori Tada‐aki 
Published: July 2010

Yamauchi M, Nagata S, Seki N, Toyama Y, Harada N, Niikawa N, Masuno I, Kajii T, Hori T. Prenatal diagnosis of fragile X syndrome by direct detection of the dynamic mutation due to an unstable DNA sequence.Clin Genet 1993: 44: 169–172. © Munksgaard, 1993The fragile X syndrome is the most common familial form of mental retardation. The mutation causing the syndrome is dynamic mutation due to an unstable DNA (CCG)n repeat localized at Xq27.3. We have previously reported a PCR procedure to prepare a diagnostic probe, pPCRfx1, which can be used to determine the genotype of fragile X mutation individuals by Southern blot analysis. In the present study, pPCRfx1 was applied to the prenatal diagnosis, using chorionic villus cells, of a fetus which was at risk of having fragile X syndrome. In the PstI assay, the Southern blot showed the typical pattern of a female carrier with the full mutation. Analysis of the DNA methylation patterns by EcoRI + EagI assay showed that the EagI restriction site was not methylated on the mutated X chromosome of chorionic villi, but the sites were totally methylated in the brain and other tissues of the fetus. Thus the fetus was diagnosed to be a heterozygous female carrier of the dynamic mutation involved in the fragile X syndrome.
Haplotype analysis at the low density lipoprotein receptor locus in normal and familial hypercholesterolemia Norwegian subjects
Authors: Rødningen Olaug K. , Leren Trond P. , Røsby Oddveig , Tonstad Serena , Ose Leiv , Berg Kare 
Published: July 2010

Rødningen OK, Leren TP, Røsby O, Tonstad S, Ose L, Berg K. Haplotype analysis at the low density lipoprotein receptor locus in normal and familial hypercholesterolemia Norwegian subjects.Clin Genet 1993: 44: 214–220. © Munksgaard, 1993We have performed haplotype analysis at the low density lipoprotein receptor (LDLR) locus in order to investigate the molecular genetics of familial hypercholesterolemia (FH) in Norway. Haplotypes were constructed using 7 restriction fragment length polymorphisms (RFLPs) in 194 subjects from 48 unrelated Norwegian FH families. Hypercholesterolemia co‐segregated with haplotypes at the LDLR locus in all 48 families. Unambiguous haplotypes could be established for 190 independent chromosomes from 51 FH heterozygotes and 44 healthy normal subjects. A total of 20 different haplotypes was found. The most frequent haplotype was haplotype 3, which accounted for 32.4% or 43.1% of the normal and defective haplotypes, respectively. Haplotype 2 was significantly more frequent among the defective alleles than among the normal alleles (33.3% and 5.8%, respectively, p<0.0001). Thus, haplotypes 2 and 3 accounted for 76.4% of the defective haplotypes. More data are needed to determine the possible existence of founder genes in the Norwegian population. Haplotypes 1, 2, 3, 5 and 8 accounted for 88.2% of the normal haplotypes. Based upon the cumulative heterozygosity index, the SphI, NcoI and 3′ ApaLI RFLPs are the most informative markers in the Norwegian population.
Suggestion of linkage between manic‐depressive illness and the enzyme phosphoglycolate phosphatase (PGP) on chromosome 16p
Authors: Eiberg H. , Ewald H. , Mors O. 
Published: July 2010

Eiberg H, Ewald H, Mors O. Suggestion of linkage between manic‐depressive illness and the enzyme phosphoglycolate phosphatase (PGP) on chromosome 16p. Clin Genet 1993: 44: 254–257. © Munksgaard, 1993Two large Danish pedigrees with manic‐depressive illness (MDI) were ascertained through bipolar probands. The pedigrees include bipolar as well as unipolar cases. An autosomal dominant mode of inheritance with incomplete penetrance was assumed. Linkage relationships between MDI and 37 autosomal serum, enzyme and blood group markers were investigated. For phosphoglycolate phosphatase, a maximum lod score of 2.20 at 0% recombination was found for the largest family. The other family was not informative. This may suggest assignment of a major gene for MDI to chromosome 16p13.
Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin expression
Authors: Dean John C. S. , Gray E. S. , Stewart K. N. , Brown T. , Lloyd D. J. , Smith N. C. , Pope F. M. 
Published: July 2010

Dean JCS, Gray ES, Stewart KN, Brown T, Lloyd DJ, Smith NC, Pope FM. Restrictive dermopathy: a disorder of skin differentiation with abnormal integrin expression.Clin Genet 1993: 44: 287–291. © Munksgaard, 1993Clinical features and histological findings in two sibs who died from restrictive dermopathy in the neonatal period are described. Fibroblasts cultured from a skin biopsy from the second sib and fibroblasts from normal neonatal skin were studied using monoclonal antibodies to visualise integrin subunits by immunocytochemistry. Restrictive dermopathy fibroblasts displayed increased expression of the alpha‐1 and alpha‐2 subunits of integrin, those responsible for collagen binding. The increase was not matrix dependent. Integrins may play an important role in tissue differentiation, and our findings support the hypothesis that restrictive dermopathy is a disorder of skin differentiation.
A mild form of mucolipidosis type III in four Baluch siblings
Authors: Ward Chandra , Singh Rashmi , Slade Christina , Fensom A. H. , Fahmy A. , Semrin A. , Sjövall A. , Talat A. , Hasilik A. , Klein I. , Benson P. F. 
Published: July 2010

Ward C, Singh R, Slade C, Fensom AH, Fahmy A, Semrin A, Sjövall A, Talat A, Hasilik A, Klein I, Benson PF. A mild form of mucolipidosis type III in four Baluch siblings.Four Baluch siblings with mucolipidosis type III (pseudo‐Hurler polydystrophy) are described. The patients had features commonly found in mucolipidosis III, including claw hands, joint stiffness, aortic valve involvement and radiological dysostosis multiplex. However, intelligence was normal, there were no eye abnormalities on slit‐lamp examination and skin elasticity was normal. Many lysosomal enzymes were elevated in serum and diminished in cultured fibroblasts, although the findings for β‐galac‐tosidase were atypical. Assays for the two enzymes involved in formation of the phosphomannose recognition marker revealed normal activity of the phosphotransferase with α‐methylmannoside as an acceptor, and normal activity of the phosphodiester glycosidase. Metabolic labelling of fibroblasts with 32P followed by immunoprecipitation of cathepsin D, electrophoresis and fluorography showed that this enzyme was not labelled in the patients' cells, although some label was detected in the secreted precursor polypeptide. The data are consistent with the assumption that activity of the phosphotransferase is low towards lysosomal enzymes as substrates, and that the patients belong to complementation group C.
11q trisomy detected by fluorescence in situ hybridization
Authors: Takano Takako , Yamanouchi Yasuko , Kawashima Shoko , Date Masatsune , Hashira Shintaro , Kida Mitsushiro , Abe Toshiaki , Nakahori Yutaka , Nakagome Yasuo 
Published: July 2010

Takano T, Yamanouchi Y, Kawashima S, Date M, Hashira S, Kida M, Abe T, Nakahori Y, Nakagome Y. 11q trisomy detected by fluorescence in situ hybridization. Clin Genet 1993: 44: 324–328. © Munksgaard, 1993A patient with psychomotor developmental delay, multiple minor anomalies, congenital heart disease and left inguinal hernia is reported. His karyotype was 45,X/46,X,+mar (3 : 37 cells), and the marker chromosome was identified as t(Y;11) (q12;q14?) using fluorescence in situ hybridization and fluorescent chromosome painting. He was diagnosed as mosaic for de novo 11q trisomy.
Disease profile of 400 institutionalized mentally retarded patients in Kuwait
Authors: Farag T. I. , Al‐Awadi S. A. , El‐Badramary M. H. , Aref M. A. , Kasrawi B. , Murthy D. S. Krishna , El‐Khalifa M. Y. , Yadav G. , Marafie M. J. , Bastaki L. , Wahba R. A. , Mohammed F. M. , Hassan S. Abul , Redha A. A. , Redha M. A. , Al‐Aboud H. , Al‐Hijji S. , Al‐Dighashem D. , Al‐Hashash N. , Al‐Jeryan L. , Al‐Khorafi H. , Qurban E. A. , Al‐Sulaiman I. 
Published: July 2010

Farag TI, Al‐Awadi SA, El‐Badramary MH, Aref MA, Kasrawi B, Krishna Murthy DS, El‐Khalifa MY, Yadav G, Marafie MJ, Bastaki L, Wahba RA, Mohammed FM, Abul Hasan S, Redha AA, Redha MA, Al‐aboud H, Al‐Hijji S, Al‐Dighashem D, Al‐Hashash N, Al‐Jeeryan L, Al‐Khor‐afi H, Qurban EA, Al‐Sulaiman I. Disease profile of 400 institutionalized mentally retarded patients in Kuwait.Clin Genet 1993: 44: 329–334. © Munksgaard, 1993In this preliminary report we summarize the results of a 4‐year multidisciplinary systematic, etiological clinicogenetic survey of 400 institutionalized mentally retarded patients in Kuwait. All had an intelligence quotient below 50. A constitutional disorder, as the direct cause of the mental retardation, was found in 203 patients (50.75%)): a chromosomal abnormality in 37 (9.25%), Mendelian disorders in 137 (34.25%), MCA/MR in 22 (5.55%) and CNS malformations in 7 cases (1.75%). In 157 patients (39.35%) a pre‐, peri or postnatal cause was ascertained. No etiological diagnosis was detected in 40 patients (10%). A detailed analysis of the “disease profile” is given and compared with the results of previous diagnostic genetic surveys among different institutionalized mentally retarded populations in Western and developing countries.
Cohen syndrome: the clinical symptoms and stigmata at a young age
Authors: Fryns Jean‐Pierre , Legius Eric , Devriendt Koen , Meire Françoise , Standaert Lieve , Baten Emiel , Van den Berghe Herman 
Published: July 2010

We present the clinical findings and follow‐up data of four female children with Cohen syndrome, two sisters and one pair of dizygotic female twins. The most characteristic findings from birth on were as follows:

Low‐normal growth parameters at birth.
Mild hypotonia and evidence of progressive microcephaly with narrow forehead in the first year of life.
Neutropenia was present from the beginning, remained unchanged over the years and is not associated with higher susceptibility to infections.
Autistic behavior and severe psychomotor retardation up to the age of 2 years. At that age the ocular anomalies with high‐grade myopia and chorioretinal dystrophy were diagnosed. Correction of the myopia resulted in a marked catch‐up in psychomotor development.
After the age of 6 years facial stigmata became more evident with short philtrum of the upper lip and broad and large upper incisors.
Tendency to truncular obesity with rest hypotonia and poor muscle development after the ages of 6 to 8 years.

The clinical findings and follow‐up data in the present four children with Cohen syndrome illustrate that the diagnosis of Cohen syndrome in infancy is very difficult.
Evaluation of a clinically applicable mutation screening technique for genetic diagnosis of familial hypercholesterolemia and familial defective apolipoprotein B
Authors: Nissen Henrik , Hansen Annebirthe B. , Guldberg Per , Hansen Torben S. , Petersen Niels E. , Harder Mogens 
Published: July 2010

We have recently developed a simple mutation screening assay based on the denaturing gradient gel electrophoresis (DGGE) technique for detection of mutations in the coding and regulatory regions of the low density lipoprotein receptor (LDLR) gene and the codon 3500 region of the apolipoprotein (apo) B‐100 gene leading to familial hypercholesterolemia (FH) and familial defective apo B‐100 (FDB), respectively. To evaluate the assay, 14 Danish families suspected of FH were studied. In ten families, the DGGE assay detected seven different point mutations, including mutations undescribed prior to establishing the assay. In addition, in one of these ten families and in one of the remaining four families, Southern blotting detected the FH‐DK3 exon 5 deletion. Based on segregation analysis and clinical data, the FH diagnosis was dubious in the remaining three families without DGGE or Southern blotting detectable mutations.In conclusion, a simple DGGE based mutation screening assay may detect underlying mutations in most FH/FDB families, thus allowing its routine use in genetic counselling of FH‐families.
Clinical, morphological and biochemical features in the familial articular hypermobility syndrome (FAHS): a family study
Authors: Garcia‐Cruz D. , Cano‐Colin S. , Sánchez‐Corona J. , Gallegos MP , Chimal‐Monroy J. , Díaz‐de‐León L. 
Published: July 2010

A female with clinical features of familial articular hypermobility syndrome (FAHS) and her family were studied. The subject showed generalized hypermobility, except for a painful shoulder which presented functional limitation with a diagnosis of painful shoulder syndrome. Biochemical studies demonstrated that collagen and glycosaminoglycans (GAGs) contents from skin biopsies of the subject and her family were almost normal. Nevertheless, the densitometric analysis of electrophoretic patterns showed differences in the relative proportions of their collagenous components. They were characterized by changes in type I and III collagens and the presence of type V collagen, in the subject, her father and brother. Also, they presented changes in the types of GAGs, when compared with those of normal skin. Morphological studies revealed a general disorganization of dermal components, a loose collagen network characterized by thick bundles. Also, besides cellular elements, the presence of an abundant darkly staining material was observed.Biochemical and morphological findings permit us to suggest a connective tissue defect, initially described in the FAHS, otherwise known as Ehlers‐Danlos syndrome (EDS) type XI.
Linkage analysis in a large Spanish family with X‐linked retinitis pigmentosa: phenotype—genotype correlation
Authors: Capeans C. , Blanco M. J. , Lareu M. V. , Barros F. , Piñeiro A. , Sanchez‐Salorio M. , Carracedo A. 
Published: July 2010

X‐linked retinitis pigmentosa (XLRP) accounts for 10–25% of RP families and causes the most severe form of the disease in terms of onset and progression. Although three different loci (RP3, RP2 and RP15) have been proposed on the short arm of the X‐chromosome by linkage analysis, RP3 represents the disease locus in the majority of XLRP families.The identification of female carriers of X‐linked RP is important for genetic counselling. The presence of fundus and electroretinogram (ERG) abnormalities have been reported to be as high as 87 and 90%, respectively. However, in clinical practice it has not always been possible to know the carrier state of females at risk.Thirty‐five members of a Spanish family with X‐linked RP were evaluated by linkage analysis using nine polymorphic markers (CYBB, DXS1110, M6, DXS6679, DXS1068, DXS1058, MAOA, MAOB and DXS6849) that map to the X‐chromosome region Xp21.1 to Xp11.3, in an attempt to determine the carrier state of these females at risk. It was possible to establish that a RP3 mutation is, most likely, segregating in this family.
Low frequency of RET mutations in Hirschsprung disease in Sweden
Authors: Svensson Pär‐Johan , Molander Marie‐Louise , Eng Charis , Anvret Maria , Nordenskjöld Agneta 
Published: July 2010

Hirschsprung disease is a congenital malformation, where absence of intramural ganglia in the hindgut results in a defect in the coordination of peristaltic movement. This leads to ileus in the newborn or, more often, constipation in children and adults. The disease affects one in 5000 live births. Siblings of affected cases are at an increased risk (4%) of developing the disease. Among cases, males are affected more often than females.The first major susceptibility gene for Hirschsprung disease is the RET proto‐oncogene on 10q11.2. Germline RET mutations in Hirschsprung disease are mainly inactivating, and have been reported to account for up to 20 and 50% of sporadic and familial cases, respectively. We have screened Swedish population‐based samples from 62 sporadic cases and seven familial cases of Hirschsprung disease with single strand conformation polymorphism (SSCP), and found five mutations.
Ethical considerations for enzyme replacement therapy in neuronopathic Gaucher disease
Authors: Elstein Deborah , Abrahamov Ayala , Zimran Ari 
Published: July 2010

Elstein D, Abrahamov A, Zimran A. Ethical considerations for enzyme replacement therapy in neuronopathic Gaucher disease. Clin Genet 1998: 54: 179–184. 0 Munksgaard, 1998Enzyme replacement therapy for Gaucher diseases, the most prevalent lysosmal storage disease, was originally approved by the FDA for type I patients and has proven to be both safe and effective in reducing hepatosplenomegaly and improving the hematological parameters. However, the use of enzyme treatment in both neuronopathic forms has heretofore been on an investigational or trial basis, with reports of progression of neurological deterioration even at very high doses. To date, there are no guidelines for clinicians with regard to enzyme replacement therapy in the neuronopathic forms of metabolic diseases. Herein, we discuss strategies derived from the literature ub‐his treatment of very premature babies and from the Jewish Halachic point of view. In conclusion, we describe recommendations for the ethical treatment and/or withdrawal of treatment. as well as practical guidelines for dosage regimens, in children with neuronopathic Gaucher disease.
Severe classical congenital muscular dystrophy and merosin expression
Authors: Vajsar Jiri , Chitayat David , Becker Laurence E. , Ho Michael , Ben‐Zeev Bruria , Jay Venita 
Published: July 2010

Vajsar J, Chitayat D, Becker LE, Ho M, Ben‐Zeev B, Jay V. Severe classical congenital muscular dystrophy and merosin expression. Clin Genet 1998: 54: 193–198. 0 Munksgaard, 1998It has been suggested that patients with autosomal recessive merosin deficient congenital muscular dystrophy (CMD), as opposed to the merosin positive cases form a homogeneous subgroup of a clinically more severe form of CMD. We examined merosin expression in muscle biopsies from five children with the severe classical form of CMD. Merosin deficiency was found only in 1 patient, a 6–year‐old female, with abnormal brain myelination. However, her initial biopsy did not reveal the classical picture of dystrophy. The four merosin positive cases exhibited severe muscle weakness but their brain imagings were normal. There were no familial cases, except for the mother of 1 patient who had a milder form of the disease, suggesting an autosomal dominant mode of inheritance.In contrast to previous reports, the merosin deficient CMD cases were rare in our group. Furthermore, merosin positive cases were also associated with severe phenotype suggesting that a severe phenotype is not exclusive to merosin deficient cases. Finally, the absence of merosin in a neonate with hypotonia and weakness can be helpful in making a definitive diagnosis of CMD, even though the dystrophic process may not be evident yet and histology may be non‐specific.
Molecular basis of cystic fibrosis in the Republic of Macedonia
Authors: Petreska L. , Koceva S. , Plaseska D. , Chernick M. , Gordova‐Muratovska A. , Fustic S. , Nestorov R. , Efremov GD 
Published: July 2010

Petreska L, Koceva S, Plaseska D, Chernick M, Gordova‐Muratovska A, Fustic S, Nestorov R, Efremov GD. Molecular basis of cystic fibrosis in the Republic of Macedonia. Clin Genet 1998: 54: 203–209. 0 Munksgaard, 1998Eighty‐three cystic fibrosis (CF) patients and their families, belonging to various ethnic groups living in the Republic of Macedonia were studied for molecular defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and for the associated extragenic marker loci XV‐2c and KM 19. The DNA methodology used included characterization of CFTR mutations in 19 exons (and flanking sequences) of the gene and analysis of distribution of the XV‐2c/KM19 haplotypes among normal (N) and CF chromosomes by polymerase chain reaction (PCR) amplification followed by dot blot hybridization, restriction digestion, single‐strand conformational polymorphism, constant denaturing gel electrophoresis, denaturing gradient gel elec‐trophoresis, and sequencing. We identified 58.4% (97/166) of the CF chromosomes. Nine different CFTR gene mutations, including three novel ones. were found. Eight known and one new CFTR intragene polymorphisrns were also characterized. The haplotype analysis of the XV‐2c/TaqI and KM19/PstI polymorphic loci have shown that haplotype C is the most frequently found haplotype among the non‐AF508 CF chromosomes from Macedonia (36.5%). The results demonstrate the broad heterogeneity of CF origin in this part of the Balkan Peninsula.
A family with three germline mutations in BRCAl and BRCA2
Authors: Liede Alexander , Metcalfe Kelly , Offit Kenneth , Brown Karen , Miller Shari , Narod Steven A. , Moslehi Roxana 
Published: July 2010

Liede A, Metcalfe K, Offit K, Brown K, Miller S, Narod SA, Moslehi R. A family with three germline mutations in BRCAl and BRCA2. Clin Genet 1998: 54: 215–218. 0 Munksgaard. 1998Several cancer genetics centres offer testing for specific BRCAl and BRCAZ mutations to Ashkenazi Jewish individuals with a family history of breast and ovarian cancers. Testing involves screening for three common mutations found in this population, namely BRCA I 185delAG, 5382insC and BRCA2 6174delT (Struewing et al., Nat Genet 1995: 11: 198–200; Roa et al., Nat Genet 1996: 14 185–187; Oddoux et al., Nat Genet 1996: 14 188–190). We have identified a large Ashkenazi Jewish kindred (W9170) with ten cases of breast cancer and four cases of ovarian carcinoma. Initially, mutation analysis for this family identified a BRCAl 185delAG mutation in the proband diagnosed with three separate primary cancers of the breast, ovary and colon. Another individual in this family diagnosed with two primary cancers of the ovary and breast, was identified as having a second mutation, BRCA I 5382insC. Subsequent work found that two sisters (cousins of the proband), both diagnosed with carcinoma of the breast, had a third mutation, BRCAZ 6174delT. These three mutations have previously been found to be more common in the Ashkenazi Jewish population (References as above). The identification of all three mutations in one family, raised new implications for the manner in which testing and counselling should be offered. In our opinion, Ashkenazi Jewish individuals in breast‐ovarian cancer families should be offered complete testing for the three common Ashkenazi Jewish mutations regardless of previous identification of one of these mutations in the family.