bluuebunny/crossref_metadata_2025 huggingface dataset:
Cockroach sensitivity in Norway: a previously unidentified problem?
Authors: Lødrup Carlsen K. C , Carlsen K. H. , Buchmann M. S. , Wikstrøm J. , Mehl R. ,   GAIN
Published: March 2003

Background: Little is known about cockroach sensitization in Scandinavia, whereas cockroaches are implicated in allergic diseases throughout large parts of the world. In association with the Genetics of Asthma International Network (GAIN) study, we report sensitization to cockroaches and possible association with IgE‐mediated diseases in Norway.

Methods: 100 Norwegian families (426 subjects) of 7–35‐year‐old sibling‐pairs with asthma and their parents underwent questionnaire/interview (medical and exposure history), skin prick test (SPT) to common local inhalant allergens and German cockroach, and IgE specific to mites, mosquito, shrimp and cockroach. Cockroach sensitization was defined as positive if there was a positive (≥ 3 mm) skin prick test and/or presence of IgE antibody of class 2 or more.

Results: Thirty‐one subjects (7.5%) were sensitized (five monosensitized) to cockroach (27 by skin prick test and seven by IgE antibody, all with additional inhalant allergy). Co‐sensitization was most common to grass (in 61%), cat (48%), dog (48%) and mites (42%). Reported allergic diseases in cockroach‐sensitized subjects were asthma and rhinitis (n = 10), asthma only (n = 9), rhinitis only (n = 2) and neither asthma nor rhinitis (n = 10).

Conclusions: Since cockroach sensitization was relatively frequent in Norwegian atopic families, albeit with unclear clinical implications, we suggest that cockroach allergy should be considered in atopic subjects with respiratory disease.
Expression and localization of heat shock proteins in rat basophilic leukemia cells: differential modulation by degranulation, thermal or oxidative stress
Authors: Bachelet M. , Marchand F. , Souil E. , François D. , Mariéthoz E. , Weyer A. , Polla B. S.
Published: March 2003

Background: Rat basophilic leukemia (RBL‐2H3) cells are well characterized in terms of morphological and biochemical changes upon activation, and have been extensively used as a model system for studying the mechanisms of the immediate hypersensitivity reaction. To investigate whether overexpression of heat shock/stress proteins (HSP) is involved in the mast cell‐dependent reactivity, we examined the adaptive responses of RBL‐2H3 cells to classical stress conditions such as heat shock or oxidative injury produced by an aqueous extract of tobacco smoke.

Methods: HSP were determined by flow cytometry and immunocytochemistry. Degranulation was confirmed as the release of β‐hexosaminidase, determined spectrophotometrically, and by electron microscopy experiments.

Results: We found that RBL‐2H3 cells respond to heat shock or oxidative injury by the synthesis of both the inducible 72 kDa HSP (Hsp70), and the oxidation‐specific 32 kDa heme oxygenase (HO)‐1. Heat shock induced mainly Hsp70 in a cell growth‐dependent manner, whereas oxidative stress induced mainly HO‐1 in a cell growth‐independent manner. However, heat shock or oxidative stress had no significant effects on degranulation.

Conclusion: Stress‐mediated synthesis of HSP was not associated with RBL‐2H3 degranulation and likewise, degranulation did not induce HSP.
Cutaneous field stimulation of sensory nerve fibers reduces itch without affecting contact dermatitis
Authors: Wallengren J.
Published: March 2003

Background: A new technique, cutaneous field stimulation (CFS), which activates electrically unmyelinated C‐fibers, is used to treat localized itch. Its action is similar to that of capsaicin, the pungent agent in hot peppers, which enhances delayed allergic reactions. The aim of the study was to investigate how experimental contact dermatitis responds to CFS.

Methods: Twelve patients with contact dermatitis in response to nickel were treated by CFS for 1 h each for four consecutive days. A flexible plate containing electrodes was applied to a test area on the upper arm and was stimulated by a constant current (0.8 mA). On the fifth day, patients were provoked by epicutaneous application of nickel sulfate (allergic contact dermatitis) and benzalkonium chloride (irritant contact dermatitis), and by intradermal tuberculin (delayed immunologic reaction). Twelve other patients with IgE‐mediated allergy were treated by CFS on the lower arm for 1 h and were then pricked with histamine and allergen extracts (wheal volume was measured) and were tested using benzoic acid (nonimmunologic contact urticaria; closed test). Ten of these patients were also treated by CFS for four days, and experiments were performed on the fifth day.

Results: Test reactions to nickel, benzalkonium, and tuberculin were found to be unaffected by CFS treatment. Although allergic prick test reactions were enhanced (by 28%) after a single CFS treatment, the associated itch was significantly reduced both after single and repeated CFS treatments (by 65% and 38%, respectively).

Conclusions: Repeated use of CFS to reduce itch has no adverse effects on contact dermatitis.
Birch and ragweed pollinosis north of Milan: a model to investigate the effects of exposure to “new” airborne allergens
Authors: Asero R.
Published: March 2003

Background: The effects of sudden and massive exposure of the general population to novel airborne allergens are not known. This study aimed to investigate the clinical effects of two “new” allergens, ragweed and birch, in an area north of Milan during the last 15 years.

Methods:  We reviewed the records of 2571 monosensitized patients seen during the last 10 years in two allergy units north of Milan. Data included age at onset of allergic symptoms, and family history of allergic diseases. In this sample, 500 were allergic to grass, mite, birch, and ragweed; 293 to pellitory; 167 to mugwort; 100 to Alternaria; and 11 to plantain.

Results: Birch pollen‐allergic patients and ragweed pollen‐allergic patients showed a similar mean age at onset (35.3 years vs. 35.1 years; P = NS), but were significantly older than all other groups of patients (P < 0.001). Patients allergic to ragweed and birch pollen, 304 and 323 respectively, were >30 years at the onset of allergic symptoms. A family history of allergic disorders among first degree relatives was far less frequent among patients allergic to birch pollen (29%) or ragweed pollen (27%) than among patients sensitive to all other airborne allergens, except those allergic to mugwort pollen (P < 0.001). In both ragweed and birch groups, a positive family history was significantly more common among subjects < 30 years than in those > 30 years at onset of respiratory allergy (81/196 (41%) vs. 54/304 (18%), P < 0.001 for the ragweed group; 80/177 [45%]vs. 65/323 (20%), P < 0.001 for the birch group).

Conclusion: Exposure of the general population of this area to two new airborne allergens resulted in the onset of respiratory allergy in many older people who lacked any relevant predisposing factor. Although we cannot exclude the possibility that those who became allergic had been exposed to birch or ragweed pollen elsewhere, a more likely explanation is a specific susceptibility that remains viable until the subject encounters the “right” allergen.
Therapeutic points of intervention and clinical implications: role of desloratadine
Authors: Bachert C.
Published: March 2003

Desloratadine, a potent, once‐daily, orally active, nonsedating, histamine H1‐receptor antagonist, inhibits the release of histamine and other inflammatory mediators. Once‐daily desloratadine therapy rapidly reduces the symptoms of perennial allergic rhinitis and seasonal allergic rhinitis (SAR), reduces the use of inhaled albuterol by patients with SAR and concomitant asthma, and improves symptoms and quality of life in patients with chronic idiopathic urticaria. An open‐label, observational study in SAR patients revealed that desloratadine therapy significantly reduced nasal, ocular, dermal, asthma, and total symptoms, and enabled half of the patients with concomitant asthma to reduce their use of asthma medications. Globally, more than 91% of patients and physicians judged desloratadine to have excellent or good efficacy, and more than 98% judged it to have excellent or good tolerability. Furthermore, desloratadine therapy improved quality of life, decreasing by more than 10‐fold the percentage of patients whose daily activities and/or sleep were moderately or severely affected by SAR. Allergic rhinitis, a major chronic airway disease that is a risk factor for asthma, warrants extended diagnostic procedures and well‐tolerated therapy that encompasses the entire airway, addresses multiple steps in the allergic inflammatory cascade, and is effective on nasal, ocular, dermal, asthma, and total symptoms.
Presence of the AZF region in a female with an idic(Y)(q11)
Authors: Jenderny J. , Schmidt W. , Held KR
Published: March 2003

In a child with some features of Turner's syndrome, gonosomal mosaicism with an isodicentric nonfluorescent (idic)Y chromosome was detected (mos 45,X/47,X,idic(Y)(q11),idic(Y)(11)/46,X,idic(Y)(q11)). Histopathological examination showed streak gonads with some evidence of ovarian stroma and no sign of gonadoblastoma. Polymerase chain reaction (PCR) analysis in blood lymphocytes and gonadal tissues using primers of seven loci along the Y chromosome, including the sex determined region (SRY), azoospermia factor region (AZF) and the deleted in azoospermia (DAZ) gene was positive for all loci tested, confirming the isodicentric character of the Y chromosome and indicating the presence of the AZF region. It is remarkable that the existence of spermatogenesis controlling genes does not play an important role in gonadal development and differentiation in a phenotypic female with some Turner stigmata. The data presented here are briefly discussed with previously‐described patients.
Autosomal dominant carpal tunnel syndrome
Authors: Stoll C. , Maitrot D.
Published: March 2003

Carpal tunnel syndrome is common in adults and is usually sporadic and idiopathic. When carpal tunnel syndrome is inherited, it is often the manifestation of a systemic disease. We report carpal tunnel syndrome in an otherwise healthy woman aged 35 years. Family history reveals that her daughter, her sister and a sister's daughter, an aunt, a first cousin, her father and the paternal grandmother are also affected. The age of onset of the disease in this family was between 9 and 52 years of age. The family in this paper demonstrates an interesting pattern of inheritance with earlier onset of symptoms in subsequent generations, suggestive of anticipation.
Lower extremity counterpart of the Poland syndrome
Authors: Silengo M , Lerone M , Seri M , Boffi P
Published: March 2003

Below‐the‐knee right leg hypoplasia and ipsilateral toe brachysyndactyly were observed in a 4‐year‐old female with an otherwise normal phenotype. Electromyographic and nerve conduction studies were normal. The Doppler evaluation was consistent with a 50% reduction in the blood supply from the femoral artery, suggesting vascular disruption as the pathogenic mechanism.Our observations support the hypothesis that a lower extremity counterpart of the Poland syndrome does exist and that the extent of limb involvement is dependent on the level of vascular disruption.
FISH and PCR analysis of the presence of Y‐chromosome sequences in a patient with Xq‐isochromosome and testicular tissue
Authors: Álvarez‐Nava Francisco , Martínez María C , González Sandra , Soto Marisol , Borjas Lisbeth , Rojas Alicia
Published: March 2003

Mixed gonadal dysgenesis includes a heterogeneous group of different chromosomal, gonadal, and phenotypic abnormalities, characterized by the presence of a testis on one side and streak or an absent gonad on the other, persistence of müllerian duct structures and/or wolffian derivatives, and a variable degree of genital ambiguity. Here, we describe a patient with virilized external genitalia and phenotypic features of Turner syndrome, whose blood karyotype was 45,X/46,X,i(Xq). The presence of a unilateral dysgenetic testis was confirmed by histopathology. Using fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR)‐based analysis to detect Y‐specific sequences, Y‐chromosome material was not detected. To date, this is the first case reported of Xq‐isochromosome associated with the presence of testicular tissue.
Further evidence from two families that craniofrontonasal dysplasia maps to Xp22
Authors: Pulleyn Lj , Winter Rm , Reardon W , McKeown C , Jones B , Hayward R , Evans R , Malcolm S
Published: March 2003

Craniofrontonasal dysplasia (CFND) is a rare X‐linked disorder that maps to a 13‐cM region on Xp22. Phenotypic features include craniosynostosis, hypertelorism and a broad nasal root with or without a bifid nasal tip. Multiple examples have been reported of males having a less severe phenotype than females. We report haplotype analyses in two CFND families over the critical region to which the gene has been mapped. In pedigree 1, a clinically unaffected male inherited the affected marker haplotype spanning the critical region. We suggest that this individual does have the CFND mutation, but has an extremely mild phenotype that is not detectable with clinical examination. Under the assumption that he is an unknown phenotype, a combined two‐point LOD score of 1.68 at zero recombination was obtained, increasing the previously reported total to 5.61 (DXS8022). The data do not narrow down the critical region. This result stresses the importance of subjecting fathers of apparently sporadic cases to a highly critical medical examination and may also explain the unequal ratio of reported female‐to‐male cases.
High frequency of tissue‐specific mosaicism in Turner syndrome patients
Authors: Nazarenko Sergey A , Timoshevsky Vladimir A , Sukhanova Natalia N
Published: March 2003

Interphase fluorescent studies of X chromosome aneuploidy in cultured and uncultured blood lymphocytes and oral mucosa epithelial cells using X centromere‐specific DNA probe in addition to standard karyotype analysis were performed in 50 females with a clinical suspicion of Turner syndrome. All the patients were previously screened for the presence of ‘hidden’ Y chromosome mosaicism, using the primers DYZ3 and DYZ. The use of fluorescence in situ hybridization (FISH) analysis of interphase nuclei of tissues from different germ layers (lymphocytes from mesoderm and buccal epithelial cells from ectoderm) improves the accuracy of detection of low‐level mosaicism. FISH studies on interphase nuclei revealed that 29% of patients with a pure form of monosomy X detected by metaphase analysis are, in fact, mosaics. The level of cells with the normal chromosomal constitution in lymphocytes of these cases as a rule was low, ranging from 3 to 18%, with an average of 7%. Two false‐positive cases and one false‐negative case of X monosomy mosaicism determined by standard cytogenetic approach were detected using FISH analysis. The majority of patients (92%) with mosaic form of Turner syndrome have considerable tissue‐specific differences in levels of X aneuploidy. Our data indicate that in cases when mosaic aneuploidy with low‐level frequency is questionable (approximately 10% and lower), the results of standard metaphase analysis should be supplemented with additional FISH studies of interphase nuclei. Tissue‐specific differences in contents of different cell lines in the same patients point to the necessity of studying more than one tissue from each patient.
A locus for autosomal recessive achromatopsia on human chromosome 8q
Authors: Milunsky Aubrey , Huang Xin‐Li , Milunsky Jeff , DeStefano Anita , Baldwin Clinton T
Published: March 2003

Autosomal recessive achromatopsia is a rare disorder characterized by total absent color vision, nystagmus, photophobia, and visual impairment, frequently leading to ‘legal blindness’. The primary defect is at the photoreceptor level, with retinal cones being absent or defective. The first locus for this disorder was mapped to chromosome 2q11. Here, we confirm the genetic mapping of a locus discovered in our studies of a kindred with Irish ancestry, but no known consanguinity, in which 5 of 12 children are affected. We have mapped the locus in this disorder in this family to chromosome 8q. Available data now narrow the region containing the putative gene to 1.2 cM.
Detection of a novel germline mutation in the von Hippel–Lindau tumour‐suppressor gene by fluorescence‐labelled base excision sequence scanning (F‐BESS)
Authors: Brieger Jürgen , Weidt Eberhard J. , Gansen Karen , Jochen Decker H.
Published: March 2003

The von Hippel–Lindau (VHL) syndrome is an inherited multi‐tumour disorder characterised by clinical heterogeneity and high penetrance. The VHL gene has been shown to be a tumour‐suppressor gene. A carrier of a germline mutation will be predisposed to a high variety of benign and malign tumours affecting different organ systems. As treatment of VHL malformations in presymptomatic stages will improve significantly the clinical outcome and the patient's quality of life, early and unambiguous detection of a germline mutation is mandatory. Direct sequencing especially of large genes might be laborious and time consuming. Therefore, most laboratories apply single strand conformational polymorphism (SSCP) analysis as an initial screening technique. Major disadvantages of this approach are the requirement of specialised equipment and a limited detection rate of about 70%. To overcome these problems, we applied the modified technique of fluorescence‐labelled base excision sequence scanning (F‐BESS).A young patient without family history of VHL with two hemangioblastoma of the cerebellum, pancreatic cysts and angiomatosis retinae was presented. Applying F‐BESS, we detected a frameshift in exon 2 as a de novo germline mutation. Direct sequencing revealed an insertion of C at position 631/632. This is a novel VHL mutation, which results in truncation of the VHL protein omitting the Elongin‐binding domain. Applying SSCP on the same DNA, no alteration could be detected. Three further family members were tested negative for the mutation by F‐BESS in accordance with lack of any clinical VHL features. As F‐BESS appears to be a reliable, fast and unexpensive method, we recommend this technique as an initial screening method.
Perinatal hypophosphatasia: diagnosis and detection of heterozygote carriers within the family
Authors: Gehring B , Mornet E , Plath H , Hansmann M , Bartmann P , Brenner Re
Published: March 2003

We report on two families in which one or two children had a severe disorder of skeletal development detected by prenatal ultrasonography. The children died postnatally and showed typical radiological and biochemical findings of perinatal hypophosphatasia. Biochemical analysis revealed a low activity of alkaline phosphatase (AP) and a high value of pyridoxal‐5‐phosphate (PLP), one of its natural substrates. The screening for mutations of the tissue nonspecific alkaline phosphatase (TNSALP) gene showed homozygosity for a point mutation (G 317→D) in the two affected children of the first family. The affected child of the second family was homozygous for a nonsense mutation (R 411→X). Family screening revealed that the determination of AP and PLP is helpful for detection of heterozygotes. However, heterozygote children had values of AP in the lower normal range during phases of rapid growth. The determination of PLP proved to be more sensitive in these cases. It should be kept in mind that during the last trimester of gestation there is an increase in maternal AP activity and a normalization of PLP due to placental AP, which is not affected. Therefore, in the course of a prenatal diagnosis in an index case, paternal blood should be analyzed in parallel. For detailed genetic counseling and early prenatal diagnosis in following pregnancies, the possibility of mutation analysis should be used.
Mexican geneticists’ views of ethical issues in genetics testing and screening. Are eugenic principles involved?
Authors: Lisker Rubén , Carnevale Alessandra , Armendares Salvador
Published: March 2003

Herein we discuss Mexican geneticists’ views of ethical issues in genetic testing and screening, analyzing whether eugenic principles are involved in this activity. The information was obtained from a comprehensive survey on genetics, ethics, and society organized by Wertz and Fletcher in 1993, in which 37 nations participated. The responses to 21 questions from 64 out of 89 (72%) geneticists invited to participate are analyzed in this paper. The questions were practically the same as those answered recently by a group of Chinese geneticists (Mao X. Chinese geneticists’ views of ethical issues in genetic testing and screening: evidence for eugenics in China. Am J Hum Genet 1998: 63: 688–695), who work in a country where the furtherance of eugenic principles is considered to be the goal of human genetics. We concluded that although there are many similarities in the answers from both countries, this is not indicative of Mexican geneticists pursuing eugenic goals because: a) there is no coercion involved; and b) there is no intention of improving the gene pool.
Mosaicism for a small marker chromosome resulting from a familial Robertsonian translocation (21;22)
Authors: Arab Sara , Chitayat David , Gardner H Allen , Winsor Elizabeth Jt
Published: March 2003

A mosaic marker chromosome found in amniotic fluid was shown to have originated from the proximal part of the long arm of chromosome 22. This marker is unusual because it is the result of a deletion of a maternally inherited Robertsonian 21;22 translocation. It is suggested that the deletion and marker formation probably occurred post zygotically in the fetus. This rare case illustrates the difficulty in estimating risk of fetal abnormalities associated with de novo marker chromosomes. In this example, although the ‘extra’ marker chromosome contains euchromatin, the karyotype may still be ‘balanced’.
Relation of mathematical ability to psychosis in Iceland
Authors: Karlsson Jon L
Published: March 2003

A study of mathematically gifted Icelanders demonstrates an increased risk of mental illness in their ranks. Psychotic disorders are also frequent among their relatives. Linkage of academic records with previously published data on the family distribution of psychosis reveals a pattern compatible with the hypothesis that high arousal plays a role in reasoning ability.
Proximal myotonic myopathy: clinical and molecular investigation of a Norwegian family with PROMM
Authors: Sun Chen , Henriksen Olaf Anton , Tranebjærg Lisbeth
Published: March 2003

Proximal myotonic myopathy (PROMM) was first described in 1994 as a multisystem disorder with similarity to myotonic dystrophy (DM), but without the abnormal (CTG)n expansion in the DM protein kinase (DMPK) gene. The inheritance is autosomal dominant and the clinical features include myotonia, proximal muscle weakness and cataract. Linkage analysis in nine German PROMM families has indicated the possibility of linkage to DM2 locus on chromosome 3. We report a Norwegian PROMM family in which the proband was clinically diagnosed as DM but without the (CTG)n expansion. Using an intragenic marker we showed that the DMPK gene did not segregate with the disease in this family. All family members are heterozygous for the R894X mutation in CLCN1 gene. Linkage analysis could not be performed, but haplotyping probably excludes the DM2 locus as the disease locus in this family. The present family emphasises that myalgia is a prominent symptom in PROMM and the clinical differences may be explained by genetic heterogeneity. This family will be reinvestigated along with the identification of candidate genes or regions in larger PROMM families.
Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2
Authors: Allan Larsen Lars , Hastrup Svendsen Ida , Møller Jensen Annette , Kanters Jørgen K , Skytt Andersen Paal , Møller Mogens , Asger Sørensen Sven , Sandøe Erik , Ramsøe Jacobsen Joes , Vuust Jens , Christiansen Michael
Published: March 2003

In a four‐generation family with long QT syndrome, syncopes and torsades de pointes ventricular tachycardia (TdP) were elicited by abrupt awakening in the early morning hours. The syndrome was associated with a novel KCNH2 missense mutation, G572R, causing the substitution of a glycine residue at position 572, at the end of the S5 transmembrane segment of the HERG K+‐channel, with an arginine residue. This segment is involved in the channel pore and the mutation may cause a reduction in the rapidly activating delayed rectifier K+ current (Ikr), or changed gating properties of the ion channel, leading to prolonged cardiac repolarization. The electrocardiograms of affected persons showed prolonged QT interval and notched T waves. Despite treatment with atenolol, 200 mg twice daily, the proband still experienced TdP episodes. Three untreated relatives of the proband died suddenly, and unexpectedly, at 18, 32, and 57 years of age. The G572R mutation is thus associated with a high mortality rate, and the clinical presentation illustrates that some mutations may not be controllable by just β‐blockade.
Molecular analysis of the 5′‐flanking region of the neurofibromatosis type 1 (NF1) gene: identification of five sequence variants
Authors: Osborn Mike , Cooper David N. , Upadhyaya Meena
Published: March 2003

Dideoxy fingerprinting was used to analyse the 5′ flanking region of the neurofibromin (NF1) gene in a panel of 380 neurofibromatosis type 1 (NF1) patients. Five polymorphisms/rare variants were identified at positions −412, −402, +16, +25 and +132, but control data indicated that these were unlikely to be of pathological significance. Promoter mutations in the NF1 gene are not, therefore, a common cause of NF1. This notwithstanding, a reporter gene assay was performed to determine if these variants could affect the expression of the NF1 gene, and all three changes in the 5′‐untranslated region (UTR) (+16, +25, +132) were found to be associated with a 60–70% increase in reporter gene expression.
Molecular analysis of Y chromosome long arm structural instability in patients with gonadal dysfunction
Authors: Jakubowski L , Jeziorowska A , Constantinou M , Kałużewski B
Published: March 2003

We have performed cytogenetic and molecular analyses of 45,X mosaics involving structurally abnormal Y chromosomes. Karyotypes were performed by standard cytogenetic methods and, in some cases, by fluorescence in situ hybridization, to distinguish monocentric and dicentric chromosomes. In addition, the deletions of Yq have been mapped using Southern blotting and polymerase chain reaction analysis. This paper provides additional information on the analysis of Y chromosome aberrations, and suggests that the stability of the Y chromosome in these instances is related to the site of the break point on Yq.
Clinical presentation and mutation identification in the NBS1 gene in a boy with Nijmegen breakage syndrome
Authors: Kleier Saskia , Herrmann M , Wittwer B , Varon R , Reis A , Horst J
Published: March 2003

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder which belongs to the group of inherited chromosomal instability syndromes. The clinical characteristics include severe microcephaly, a dysmorphic facies, and immunodeficiency with predisposition to malignancies. While the cellular characteristics of ataxia teleangiectasia (AT) and NBS are similar, the clinical findings are quite distinct. NBS patients show characteristic microcephaly, which is rare in association with AT and they do not develop ataxia and teleangiectasia. Recently, the gene mutated in NBS has been identified. Here we report a 5‐year‐old Bosnian boy with severe microcephaly. Because of multiple structural aberrations involving chromosomes 7 and 14 typical for AT (MIM 208900) and NBS (MIM 251260), AT was diagnosed. We suggested the diagnosis of NBS because of the boy's remarkable microcephaly, his facial appearance, and the absence of ataxia and teleangiectasia. DNA analysis was performed and revealed that the boy is homozygous for the major mutation (657del5) in the NBS1 gene. This finding confirms the diagnosis of NBS in our patient and offers the possibility to perform a most reliable prenatal diagnosis in a further pregnancy.
A novel mutation in the HEXA gene specific to Tay–Sachs disease carriers of Jewish Iraqi origin
Authors: Karpati M. , Peleg L. , Gazit E. , Akstein E. , Goldman B.
Published: March 2003

An increased frequency of carriers of 1:140, as defined by reduced hexosaminidase A (HexA) activity, was observed among Iraqi Jews participating in the Tay–Sachs disease (TSD) carrier detection program. Prior to this finding, TSD among Jews had been restricted to those of Eastern European (Ashkenazi) and Moroccan descent with carrier frequencies of 1:29 and 1:110 for Jews of Ashkenazi and Moroccan extraction, respectively. A general, pan‐ethnic frequency of approximately 1:280 has been observed among other Jewish Israeli populations. Analysis of 48 DNA samples from Iraqi Jews suspected, by enzymatic assay, to be carriers revealed a total of five mutations, one of which was novel. In nine carriers (19%), a known mutation typical to either Ashkenazi or Moroccan Jews was identified. ΔF304/305 was detected in four individuals, and +1278TATC in three. G269S and R170Q each appeared in a single person. The new mutation, G749T, resulting in a substitution of glycine to valine at position 250 has been found in 19 of the DNA samples (40%). This mutation was not detected among 100 non‐carrier, Iraqi Jews and 65 Ashkenazi enzymatically determined carriers. Aside from Ashkenazi and Moroccan Jews, a specific mutation in the HEXA gene has now also been identified in Jews of Iraqi descent.
Brachytelephalangic dwarfism due to the loss of ARSE and SHOX genes resulting from an X;Y translocation
Authors: Seidel J , Schiller S , Kelbova C , Beensen V , Orth U , Vogt S , Claussen U , Zintl F , Rappold GA
Published: March 2003

Here we report an 8‐year‐old male patient who had mesomelic shortening of forearms and legs, brachytelephalangia and ichthyotic skin lesions. Chromosomal analysis showed an X;Y translocation involving the short arm of the X chromosome (Xp). Fluorescence in situ hybridization (FISH) and molecular studies localized the breakpoints on Xp22.3 in the immediate vicinity of the KAL gene demonstrating deletions of steroid sulfatase (STS), arylsulfatase E (ARSE), and short stature homeo box (SHOX) genes. It was suspected that the patient was suffering from chondrodysplasia punctata because of a loss of the arylsulfatase E (ARSE) gene. However, no stippled epiphyses were to be seen in the neonatal radiograph. Interestingly, this patient is the first case with a proven loss of the ARSE gene without chondrodysplasia punctata, assuming that chondrodysplasia punctata is not an obligatory sign of ARSE gene loss. Brachytelephalangia was the only result of ARSE gene deletion in this case.  The patient's mother also had dwarfism and showed Madelung deformity of the forearms. She was detected as a carrier of the same aberrant X chromosome. The male patient did not show Madelung deformity, demonstrating that Lerri–Weill syndrome phenotype may be still incomplete in children with SHOX gene deletion. The wide clinical spectrum in the male and the Leri–Weill phenotype in his mother are the results of both a deletion involving several sulfatase genes in Xp22.3 and the SHOX gene located in the pseudoautosomal region. Nevertheless, there is no explanation for the absence of chondrodysplasia punctata despite the total loss of the ARSE gene.  Further studies are necessary to investigate genotype/phenotype correlation in cases with translocations or microdeletions on Xp22.3, including the ARSE and the SHOX gene loci.
A non‐sex chromosome marker in a patient with an atypical Ullrich–Turner phenotype and mosaicism of 46,X,mar/46,XX
Authors: Gray BA , Bent‐Williams A , Wolff DJ , Zori RT
Published: March 2003

The absence of a sex chromosome in conjunction with the presence of a marker chromosome generally implicates a sex chromosome origin for such marker chromosomes. These types of findings are frequently associated with Ullrich–Turner syndrome. We report a patient that presented with an atypical Ullrich–Turner phenotype and a cytogenetic mosaicism of 46,X,mar/46,XX. The marker chromosome was derived from chromosome 20, not from the X or Y chromosome. The patient's clinical features are described and discussed relative to the cytogenetic findings. This case further demonstrates the necessity of marker chromosome identification for accurate phenotype–karyotype correlation.
De novo inverted duplication of chromosome 7(q21.3→q35): cytogenetic diagnosis confirmed by FISH analysis
Authors: Back E , Toder R , Fuchshuber A
Published: March 2003

We report on a newborn female patient with a de novo pure partial duplication of 7q. The clinical features are compared with those of 19 cases from the literature with pure partial duplication of different segments of 7q. Conventional cytogenetic investigation led to the diagnosis of duplication of bands q21.3 to q35. This was confirmed by chromosome painting and by fluorescence in situ hybridization with different YAC probes from the duplicated region.
Familial deletion of (8)(q24.13q24.22) associated with a normal phenotype
Authors: Batanian JR , Morris K , Ma E , Huang Y , McComb J
Published: March 2003

We report a familial deletion of (8q) detected in amniocytes of a fetus with a normal ultrasound and in the phenotypically normal mother, who has now had three pregnancy losses. Chromosome analysis of amniocytes and maternal peripheral blood cells showed an interstitial deletion of (8)(q24.13q24.22), which is distal to the region associated with Langer–Giedion syndrome (LGS) or trichorhinophalangeal (TRP) syndrome. This deletion was confirmed by fluorescence in situ hybridization with a c‐myc cosmid clone and chromosome 8 painting library.
Homozygosity in Huntington's disease: new ethical dilemma caused by molecular diagnosis
Authors: Alonso ME , Yescas P , Rasmussen A , Ochoa A. , Macías R , Ruiz I , Suástegui R
Published: March 2003

Huntington's disease (HD) is a degenerative disorder of the central nervous system with autosomal dominant inheritance. Genetic counseling has always been difficult in this disorder with anguish, depression and denial being very common in both the patient and family members. The discovery of the causal gene has led to precise diagnostic procedures allowing homozygotes for the disease to be identified. Contrary to what occurs in some other autosomal dominant diseases, the course of the disease is not more severe in the homozygote than in the heterozygote. The present authors describe a family comparing two affected siblings: one is heterozygotic and the other homozygous for the HD mutation. They confirm that the age and symptoms of onset did not differ significantly between the subjects; however, the disease seemed to have a more severe progression in the heterozygote than in the homozygote. The authors discuss the ethical dilemma derived from the genetic counseling of a homozygotic patient, given the fact that all his offspring will be affected. Letting the offspring know about their 100% probability of inheriting the disorder is equivalent to delivering a non‐requested predictive test, while not informing them constitutes withholding crucial information from the individual.
Apolipoprotein E gene polymorphism in cerebrovascular disease: a case–controlstudy
Authors: Luthra K , Prasad K , Kumar P , Dwivedi M , Pandey RM , Das N
Published: March 2003

The association between apolipoprotein E (apo E) polymorphism and stroke has been controversial. So far there are no studies reported on the polymorphism of apolipoprotein E in cerebrovascular diseases in the Asian Indians. A blinded case–control study was therefore undertaken and the apo E genotypes and lipid profile of a total of 120 subjects (63 stroke patients and 57 healthy controls) were done. The frequency distribution of apo E alleles and genotypes were assessed and their relation with the occurrence of stroke in Asian Indian subjects was determined. A significantly high frequency of apo ε4 allele (30%) was observed in the stroke patients than the controls (11%) (p < 0.005), and patients with ε4 allele had a fourfold higher odds to develop stroke OR (95%CI) 4.2 (1.8–10.1) (p < 0.005). On multivariate analysis, after adjusting for age, triglycerides and hypertension, the association of ε4 allele with stroke was found to be no longer statistically significant, OR (95%CI) 1.2 (0.4–4.5) (p = NS). On multiple logistic regression analysis age, OR (95%CI) 1.1 (1.1–1.2) (p < 0.001), and hypertension OR (95%CI) 15.1 (2.6–89.1) (p < 0.005) were found to be independent risk factors for development of stroke. This is the first report to have examined the association of apo E gene polymorphism with stroke in the Asian Indians. This study suggests that apo ε4 allele, triglycerides, age and hypertension are the predictors for stroke development.
657del5 mutation in the NBS1 gene is associated with Nijmegen breakage syndrome in a Turkish family
Authors: Tekin M , Doğu F , Taçyıldız N , Akar E , İkincioğullari A , Oğur G , Yavuz G , Babacan E , Akar N
Published: March 2003

We report on a consanguineous Turkish family whose first son died of anal atresia and whose second son presented with severe pre‐ and post‐natal growth retardation as well as striking microcephaly, immunodeficiency, congenital heart disease, chromosomal instability and rhabdomyosarcoma in the anal region. The proband was found to carry the homozygous 657del5 mutation in the NBS1 gene, which is responsible for Nijmegen breakage syndrome (NBS) in most of the Slav populations. Our family, the first diagnosed with NBS in the Turkish population, represents one of the most severely affected examples of the syndrome, with profound pre‐ and post‐natal growth retardation associated with structural abnormalities, and expands the clinical spectrum of this rare disorder.
Supernumerary marker chromosomes derived from chromosome 15: analysis of 32 new cases
Authors: Eggermann K , Mau UA , Bujdosó G , Koltai E , Engels H , Schubert R , Eggermann T , Raff R , Schwanitz G
Published: March 2003

Small supernumerary marker chromosomes (SMC) are a heterogeneous group of chromosomes with an estimated frequency of approximately 0.14–0.72 per 1000 newborns and higher frequencies in particular populations such as the mentally retarded or infertile males. With a frequency of about 50%, derivatives of chromosome 15 represent the most common SMC. Here we present the results of a detailed analysis of 32 SMC(15) carriers who were ascertained in pre‐ or post‐natal routine cytogenetic diagnostics. SMC(15) with euchromatic content led to mental and psychomotor retardation. In contrast, SMC(15) without euchromatin were found to have no influence on the carrier's phenotype but were detected with a high incidence among infertile males. The majority of SMC(15) are pseudodicentric homologous rearrangements. Based on our investigations a further characterization of der(15) was possible.
Homologous telomere association of 19q in a female with premature ovarian failure
Authors: Zahed L , Darwiche N , Batanian JR , Awwad J
Published: March 2003

Premature ovarian failure (POF) may be due to a variety of genetic mechanisms. We report here, for the first time, telomere association of the long arms of chromosome 19, identified at low frequency (1%) in the peripheral blood cultures of a 30‐year‐old female with POF. Repeat cultures identified, in addition, the presence of 16q and 22q associations at a lower frequency (0.5%). These consistent observations are suggestive of a non‐random event. Their association with POF may just be coincidental or may hypothetically explain it by an abnormal mechanism of chromosome separation, a constitutional telomere anomaly or an unidentified chromosome instability disorder.
Genetic landmarks through philately: Luís Morquio 1867–1935
Authors: Chudley AE , Chakravorty C
Published: March 2003

Chudley AE. Genetic landmarks through philately: Luís Morquio 1867–1935.  Clin Genet 2002: 62: 438–439. © Blackwell Munksgaard, 2002

Morquio syndrome, also known as Mucopolysaccharidosis Type IV, is well known to pediatricians and geneticists, although it is rare. Many do not know much about the physician who first described this lysosomal disorder. In this brief review, the person and the disease are described, along with philatelic illustrations that have been issued to honor this famous Latin American medical hero.
Characterization of partial trisomy 9p due to insertional translocation by chromosomal (micro)FISH
Authors: De Pater JM , Ippel PF , Van Dam WM , Loneus WH , Engelen JJM
Published: March 2003

de Pater JM, Ippel PF, van Dam WM, Loneus WH, Engelen JJM. Characterization of partial trisomy 9p due to insertional translocation by chromosomal (micro)FISH.  Clin Genet 2002: 62: 482–487. © Blackwell Munksgaard, 2002

We describe a family with an insertion 12;9 translocation occurring in a balanced form in a mother and two sons, but in an unbalanced form in the proband, resulting in trisomy of chromosome region 9p22→9p24. The proband manifests typical features of trisomy 9p; the clinical signs were mental and growth retardation, microcephaly, epicanthus, low‐set ears, micrognathia, clinodactyly and hypoplastic phalanges of the fifth fingers, hypoplasia or absence of toenails, and extremely small genitals. The GTG‐banded findings were confirmed using (micro)FISH. Intriguingly, the mother and the two carrier sons exhibited major learning difficulties that were not present in the non‐carrier sister of the mother: this may be due to a gene disruption or induction of abnormal expression. Dysmorphic features were not present in the three carriers. We compare our clinical and cytogenetic findings with other cases of partial trisomy 9p reported in the literature.
Genetic technologies, health care policy and the patent bargain
Authors: Caulfield TA , Knoppers BM , Gold ER , Sheremeta LE , Bridge PJ
Published: March 2003

The idea of granting patents on human genetic material continues to cause controversy. The debate is largely focussed on the moral acceptability of human gene patents, the impact of gene patents on the research environment and the value of patents to stimulate innovation and the commercialization and dissemination of genetic discoveries. As highlighted by a recent controversy in Canada, patents can also have a profound effect on health policy and access to genetic services. Creative and bold patent reform initiatives are necessary to ensure that society will, to the highest degree possible, reap the health care benefits of the genetic revolution.
Intragraft cytokine expressionf in tolerant rat renal allografts with rapamycin and cyclosporin immunosuppression
Authors: Saggi Bh , Fisher Ra , Naar Jd , Bu D , Obias V , Tawes Jw , Wakely Jr Paul E , Posner Mp
Published: March 2003

The Th‐1/Th‐2 paradigm proposes clonal expansion of Th‐2 lymphocytes as the basis of tolerance towards allografts. Intragraft cytokine expression was evaluated in a highly stringent model of renal transplantation. ACI and Lewis rats were used as donors and recipients, respectively, for heterotopic renal transplantation. Group A (n=8) received a single dose of rapamycin and cyclosporin 12 h prior to engraftment, followed by 7 d of cyclosporin post‐operatively. Isografts (Group B, n=5) and control allografts (Group C, n=4) received no immunosuppression. Sacrifice was performed after 120 d. Intragraft expression of IL‐10, IL‐4, and IFN‐Γ was determined using qualitative reverse transcriptase‐polymerase chain reaction (RT‐PCR). All groups had functionally normal grafts at sacrifice, with 50% histological tolerance among Group A animals. No isografts showed evidence of cellular infiltrate, and all control allografts showed severe rejection. IL‐10 was only detected in the tolerant animals (p<0.001). Similarly, IL‐4 was detected predominantly in the tolerant allografts (p<0.05). IFN‐Γ was only isolated in rejected allografts, whether treated or untreated (p<0.001). We conclude that the expansion of Th‐2 cells is associated with tolerance, while the expansion of Th‐1 cells is associated with acute cellular rejection.
Tacrolimus vs Neoral in renal and renal/pancreas transplantation
Authors: Ghasemian S Reza , Light Jimmy A , Currier Charles , Sasaki Truman M , Aquino Alex
Published: March 2003

In a retrospective analysis we compared the outcome of a group of 63 kidney or kidney/pancreas transplant recipients who were transplanted between June 1994 and February 1997 and received either tacrolimus (FK, n=22) or Neoral (NEO, n=41) as part of a triple immunosuppressive protocol. Ten patients in the NEO group had recurrent rejection episodes between 1 and 8 months post‐transplant and were converted to FK. CellCept was the secondary immunosuppressive agent in about half the FK, three‐quarters of the NEO, and in all but one in the conversion (CON) groups. Patients in all groups were on prednisone in equal amounts. Mean duration of follow‐up for FK, NEO and CON groups was 32, 19 and 13 months, respectively. One‐yr patient and graft survival was 100% in all groups. At 2 yr, graft survival was 95, 96 and 100% in FK, NEO and CON groups, respectively. Acute rejection at 1 yr was twice as high in the NEO group as the FK group. There were no rejection episodes among the FK patients who also received CellCept. The mean current serum creatinines (mg%) were: FK=1.6, NEO=1.8, CON=1.9. Recurrent infection was more common with FK (8/22) than NEO (1/31) (p=0.023). Our experience suggests there is less rejection but more infection in recipients treated with FK compared to NEO. In patients with recurrent rejection, conversion from NEO to FK stabilizes renal function and minimizes subsequent rejection episodes.
Successful cytokine treatment of aplastic anemia following living‐related orthotopic liver transplantation for non‐A, non‐B, non‐C hepatitis
Authors: Sato Sumihiko , Fuchinoue Shohei , Abe Masahiro , Kitajima Kumiko , Tojimbara Tamotsu , Nakajima Ichiro , Agishi Tetsuzo , Shiraga Hiroshi , Ito Katsumi , Takasaki Ken , Hashimoto Etsuko , Hayashi Naoaki , Tanaka Koichi
Published: March 2003

The relationship between aplastic anemia and viral hepatitis is well recognized, and such patients usually have a high mortality. We successfully treated a case of aplastic anemia following living‐related orthotopic liver transplantation (LROLT) for non‐A, non‐B, non‐C hepatitis.A 2‐yr‐old boy with fulminant hepatic failure from non‐A, non‐B, non‐C hepatitis received LROLT. Before transplantation, he had pancytopenia which was probably hepatitis associated, and viral suppression was suspected after bone marrow (BM) biopsy. After the transplantation, he developed progressive pancytopenia and a diagnosis of aplastic anemia was made via BM biopsy. With immunosuppressant agents (cyclosporine, methylprednisolone), cytokine therapy (granulocyte‐colony stimulating factor (G‐CSF), macrophage‐colony stimulating factor (M‐CSF), recombinant human erythropoietin (rhEPO)) was effectual and the patient recovered from pancytopenia. He was discharged from the hospital 57 d after the liver transplantation and remains well 1 yr after LROLT. Combined cytokine therapy with high doses of G‐CSF, M‐CSF and rhEPO appeared to be effective in the treatment of aplastic anemia following liver transplantation for non‐A, non‐B, non‐C hepatitis. Since M‐CSF activates macrophages, it may have contributed to the graft rejection. Careful consideration should be given to the use of high‐dose M‐CSF in liver transplant patients.