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E Pras

Publications and source records attributed to E Pras.

At least 37 records · Page 2Linked to original sources
PubMed2001

A gene causing autosomal recessive cataract maps to the short arm of chromosome 3.

BACKGROUND: Fourteen loci have been associated with autosomal dominant cataract, but only one with the recessive form of the disease. OBJECTIVES: To find the chromosomal location of a gene causing autosomal recessive cataract in three inbred Arab families. METHODS: A single nucleotide polymorphism-based genome-wide search, with the Effvmetrix GeneChip HuSNP genotyping array, was performed on a pooled DNA sample from six affected family members in a search for regions showing homozygosity. Using conventional microsatellite markers, regions of homozygosity were further analyzed in all the families. RESULTS: A region on chromosome 3p spanning 43 megabases showed homozygosity with 13 consecutive SNPs. Three microsatellite markers from this region yielded lod scores > 3.00. A maximal two-point lod of 4.83 was obtained with the marker D3S1298 at theta = 0.004. Haplotype analysis placed the disease gene in a 20 Mb interval between D3S1768 and D3S2409. CONCLUSIONS: A gene causing autosomal recessive cataract maps to the short arm of chromosome 3.

Arabs↗
PubMed2000

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Journal Article↗
PubMed2000

Protracted febrile myalgia of familial Mediterranean fever. Mutation analysis and clinical correlations.

Protracted febrile myalgia (PFM) is a rare form of vasculitic disease that affects patients with familial Mediterranean fever (FMF). Mutation analysis performed in 15 patients who suffered from this disorder showed that 9 of the 15 patients were homozygous for M694V. FMF in these 9 patients was associated with more severe symptoms compared to a group of 30 M694V homozygous FMF patients without PFM.

Adolescent↗
PubMed2000

The founder mutations in the BRCA1, BRCA2, and ATM genes in Moroccan Jewish women with breast cancer.

To gain insight into the molecular mechanisms underlying the inherited predisposition to breast cancer in non-Ashkenazi Jews, we genotyped 54 Jewish Moroccan women with breast cancer, unselected for family history of cancer, for the predominant Jewish mutations in BRCA1, BRCA2, and ATM. One patient (2%) was found to have the 185de1AG BRCA1 mutation, none was a carrier of the 6174delT BRCA2 mutation, and 2/54 (4%) were heterozygous for the ATM mutation. These rates were not significantly different from the rates in the general non-Ashkenazi population. These preliminary data may indicate that the predominant Jewish mutations in BRCA1, BRCA2, and ATM genes contribute little, if any, to breast cancer predisposition and risk among Moroccan Jews.

Adult↗
PubMed2000

Genotype-phenotype assessment of common genotypes among patients with familial Mediterranean fever.

OBJECTIVE: To study genotype-phenotype correlation for the 4 most common genotypes found among patients with familial Mediterranean fever (FMF). METHODS: Thirty patients with the M694V/M694V genotype, 32 with M694V/V726A genotype, 25 with M694V/E 148Q genotype, and 21 with V726A/V726A genotype were assessed for various clinical manifestations of FMF, and overall disease severity. RESULTS: Patients with the M694V/M694V genotype were found to have an earlier age of onset, higher frequency of joint involvement, higher frequency of erysipelas-like erythema, and required higher doses of colchicine to control the disease compared to the other 3 genotypes. CONCLUSION: The M694V/M694V genotype is associated with more severe disease compared to other common genotypes in patients with FMF.

Age of Onset↗
PubMed2000

A nonsense mutation (W9X) in CRYAA causes autosomal recessive cataract in an inbred Jewish Persian family.

PURPOSE: To identify the genetic defect causing autosomal recessive cataract in two inbred families. METHODS: Linkage analysis was performed with polymorphic markers close to 14 loci previously shown to be involved in autosomal dominant congenital cataract. In one of the families a gene segregating with the disease was analyzed by single-strand conformation polymorphism (SSCP) and eventually sequenced. RESULTS: Three polymorphic markers close to the CRYAA gene located on chromosome 21q segregated with the disease phenotype in one of the families, but not in the other. Sequencing of the CRYAA in this Jewish Persian family revealed a G-to-A substitution, resulting in the formation of a premature stop codon (W9X). CONCLUSIONS: A nonsense mutation in the CRYAA gene causes autosomal recessive cataract in one family. This constitutes the first description of the molecular defect underlying nonsyndromic autosomal recessive congenital cataract. That there was no linkage to this locus in another family provides evidence for genetic heterogeneity.

Cataract↗
PubMed2000

Cystinuria at the turn of the millennium: clinical aspects and new molecular developments.

Cystinuria is caused by a defect in a transport molecule in the kidney and small intestine resulting in urinary excretion of cystine and the dibasic amino acids. Traditionally, three types have been recognized, but this classification correlates poorly with the findings of molecular analysis, and a new system is needed. Persons who are homozygous and heterozygous for non-Type I cystinuria can be distinguished by urinary amino acid excretion: the former secrete large amounts of cystine and all three dibasic amino acids, whereas the latter secrete more lysine and cystine than arginine and ornithine. The first gene found that is important in cystine transport is SLC3A1, located on chromosome 2p. More than 40 mutations have been identified, all associated with Type I cystinuria. The gene associated with non-Type I disease maps to chromosome 19, called SLC7A9, encodes a protein that apparently interacts with the product of the SLC3A1 gene. Almost 40 disease-associated mutations have been identified in SLC7A9, and there is some evidence that cystinuria in some patients reflects mutations in both genes. Mutations in other proteins with which the SLC3A1 and SLC7A9 products associated may be responsible for still other cases of cystinuria. Contemporary molecular knowledge has not offered any new treatment for the short term.

Amino Acid Transport Systems, Basic↗
PubMed1999

Late-onset familial Mediterranean fever (FMF): a subset with distinct clinical, demographic, and molecular genetic characteristics.

To determine the prevalence and characterize demographic, clinical, and genetic features of familial Mediterranean fever (FMF) of late onset, all patients experiencing their first FMF attack at age 40 years or more were identified using the computerized registry of our FMF clinic, and then thoroughly interviewed and examined. The control group consisted of 40 consecutive FMF patients, who arrived at the FMF clinic for their regular follow-up visit and were 40 years of age or older at the time of the examination. The severity of the disease in patients and controls was determined using a modified score, developed previously. Mutational analysis in the FMF gene was performed using a commercial kit. Only 20 of 4000 (0.5%) patients had late-onset FMF. These patients were mostly men, of non-North African origin, P < 0.05 compared to controls. All had abdominal attacks and in most these were the only manifestation of their disease, P < 0.001. None had chronic or prolonged manifestations of FMF, for example, amyloidosis, chronic arthritis, or protracted myalgia, P < 0.001. The response to treatment was good despite using low colchicine dose, P < 0.05. The overall severity score indicated a mild disease, P < 0.001. Mutational analysis revealed absence of M694V homozygosity, P < 0.01, compared to our regular FMF population. We conclude that the onset of FMF in a late age defines a milder form of disease with typical clinical, demographic, and molecular genetic characteristics.

Adult↗
PubMed1999

Refined mapping of the CSNU3 gene to a 1.8-Mb region on chromosome 19q13.1 using historical recombinants in Libyan Jewish cystinuria patients.

Cystinuria is a genetic disease manifested by the development of kidney stones. In some patients, the disease is caused by mutations in the SLC3A1 gene located on chromosome 2p. In others, the disease is caused by a gene that maps to chromosome 19q, but has not yet been cloned. Cystinuria is very common among Jews of Libyan ancestry living in Israel. Previously we have shown that the disease-causing gene in Libyan Jews maps to an 8-cM interval on chromosome 19q between the markers D19S409 and D19S208. Several markers from chromosome 19q showed strong linkage disequilibrium, and a specific haplotype was found in more than half of the carrier chromosomes. In this study we have analyzed Libyan Jewish cystinuria families with eight markers from within the interval containing the gene. Seven of these markers showed significant linkage disequilibrium. A common haplotype was found in 16 of the 17 carrier chromosomes. Analysis of historical recombinants placed the gene in a 1.8-Mb interval between the markers D19S430 and D19S874. Two segments of the historical carrier chromosome used to calculate the mutation's age revealed that the disease-causing mutation was introduced into this population 7-16 generations ago.

Alleles↗
PubMed1999

Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome: clinical characteristics and outcome.

We report 28 patients (20 male) with a syndrome characterized by abrupt onset of fever, malaise, aphthous stomatitis, tonsillitis, pharyngitis, and cervical adenopathy (PFAPA syndrome). Episodes of fever occurred at intervals of 5.1 +/- 1.3 weeks beginning at the age of 4.2 +/- 2.7 years. Fever, malaise, tonsillitis with negative throat cultures, and cervical adenopathy were reported in all 28 patients, aphthae in 19, headache in 5, abdominal pain in 5, and arthralgia in 3. Mild hepatosplenomegaly was observed in 6 patients. Mild leukocytosis, elevation of the erythrocyte sedimentation rate, and fibrinogen were found during attacks. These episodes of illness resolved spontaneously in 4.3 +/- 1.7 days. Serum IgD was found elevated (>100 U/mL) in 12 of the 18 patients tested (140.2 +/- 62.4 U/mL). Affected children grow normally, have no associated diseases, and have no long-term sequelae. Attacks were aborted by a single dose of oral prednisone (2 mg/kg) at the beginning of the attack in all 15 patients in whom this medication was prescribed. In 9 patients the syndrome has completely resolved (beginning at the age of 2.9 +/- 1.3 and lasting 8 +/- 2.5 years). In 3 other patients complete resolution of the attacks occurred after tonsillectomy was performed. PFAPA is sporadic, and no ethnic predilection was found. Increased awareness of the clinical syndrome has resulted in more frequent diagnosis and adequate treatment.

Age of Onset↗
PubMed1999

Long-term results of preoperative intra-arterial doxorubicin combined with neoadjuvant radiotherapy, followed by extensive surgical resection for locally advanced soft tissue sarcomas of the extremities.

BACKGROUND AND PURPOSE: In the 1980s a combined modality therapy of intraarterial doxorubicin, neoadjuvant radiotherapy and surgery was initiated at the Groningen University Hospital as a limb-saving treatment for locally advanced, primarily irresectable high-grade soft tissue sarcomas (STS) of the extremities. This study presents the short- and long-term results. PATIENTS AND METHODS: Between 1983 and 1987, 11 patients were treated with intraarterial doxorubicin, preoperative radiotherapy (10 x 3.5 Gy) and surgical resection. Non-radical resections received additional postoperative radiotherapy of 20-30 Gy. RESULTS: The limb-salvage rate was 91%, without local recurrences during a median follow-up of 84 months. Six patients died (55%); five from metastatic disease (45%). There were five long-term survivors with a median follow-up of 10 years. Three patients (60%) suffered serious late complications, resulting in disabilitating limb function. CONCLUSION: Although this approach is feasible as a limb-saving treatment for these unfavorable STS, long-term morbidity is high.

Adult↗
PubMed1999

The importance of family history in young patients with endometrial cancer.

Endometrial cancer occurs primarily in postmenopausal women older than 60 years of age. Especially in young patients with endometrial cancer, a positive family history with respect to cancer and/or development of synchronous or metachronous tumors can be indicative of hereditary factors. One genetic disorder, playing an important role in the development of endometrial cancer in young women, is hereditary non-polyposis colorectal cancer (HNPCC). The mean age to develop endometrial cancer because of a mutation in one of the HNPCC-genes is below 50 years. Mutation carriers have a life-time risk of about 50% for endometrial cancer. Especially young patients with endometrial cancer should always be asked for the family history and after primary treatment the family history should regularly be updated during follow-up.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1999

Topical anesthesia using lidocaine gel for cataract surgery.

PURPOSE: To assess the safety and efficacy of topical anesthesia using lidocaine gel in cataract surgery. SETTING: Department of Ophthalmology, Meir Hospital, Sapir Medical Center, Kfar-Saba, Israel. METHODS: One hundred cataract procedures (48 manual extracapsular cataract extraction [ECCE] and 52 phacoemulsification) were performed using lidocaine 2% gel as the sole anesthetic agent. The gel was applied 3 to 5 times prior to surgery. Intraoperative and postoperative data were recorded, and patients were asked to grade the pain on a scale of 0 (no pain) to 10 (unbearable pain). RESULTS: Sixty-two percent of patients having manual ECCE and 74% having phacoemulsification reported no pain during surgery (score 0). The mean pain score in the manual ECCE group was 0.99 +/- 1.64 (SD); 3 patients required an additional intracameral lidocaine injection. The mean score in the phacoemulsification group was 0.72 +/- 1.47; no patient required additional anesthesia. CONCLUSIONS: Topical application using lidocaine 2% gel is safe and highly effective, especially in clear corneal phacoemulsification. The gel also provides prolonged lubrication, further facilitating surgery.

Anesthesia, Local↗
PubMed1999

Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT.

Cystinuria (MIM 220100) is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids. Mutations in SLC3A1, encoding rBAT, cause cystinuria type I (ref. 1), but not other types of cystinuria (ref. 2). A gene whose mutation causes non-type I cystinuria has been mapped by linkage analysis to 19q12-13.1 (Refs 3,4). We have identified a new transcript, encoding a protein (bo, +AT, for bo,+ amino acid transporter) belonging to a family of light subunits of amino acid transporters, expressed in kidney, liver, small intestine and placenta, and localized its gene (SLC7A9) to the non-type I cystinuria 19q locus. Co-transfection of bo,+AT and rBAT brings the latter to the plasma membrane, and results in the uptake of L-arginine in COS cells. We have found SLC7A9 mutations in Libyan-Jews, North American, Italian and Spanish non-type I cystinuria patients. The Libyan Jewish patients are homozygous for a founder missense mutation (V170M) that abolishes b o,+AT amino-acid uptake activity when co-transfected with rBAT in COS cells. We identified four missense mutations (G105R, A182T, G195R and G295R) and two frameshift (520insT and 596delTG) mutations in other patients. Our data establish that mutations in SLC7A9 cause non-type I cystinuria, and suggest that bo,+AT is the light subunit of rBAT.

Amino Acid Sequence↗
PubMed1999

Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population.

Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever with serositis or synovitis. The FMF gene (MEFV) was cloned recently, and four missense mutations were identified. Here we present data from non-Ashkenazi Jewish and Arab patients in whom we had not originally found mutations and from a new, more ethnically diverse panel. Among 90 symptomatic mutation-positive individuals, 11 mutations accounted for 79% of carrier chromosomes. Of the two mutations that are novel, one alters the same residue (680) as a previously known mutation, and the other (P369S) is located in exon 3. Consistent with another recent report, the E148Q mutation was observed in patients of several ethnicities and on multiple microsatellite haplotypes, but haplotype data indicate an ancestral relationships between non-Jewish Italian and Ashkenazi Jewish patients with FMF and other affected populations. Among approximately 200 anonymous Ashkenazi Jewish DNA samples, the MEFV carrier frequency was 21%, with E148Q the most common mutation. Several lines of evidence indicate reduced penetrance among Ashkenazi Jews, especially for E148Q, P369S, and K695R. Nevertheless, E148Q helps account for recessive inheritance in an Ashkenazi family previously reported as an unusual case of dominantly inherited FMF. The presence of three frequent MEFV mutations in multiple Mediterranean populations strongly suggests a heterozygote advantage in this geographic region.

Amino Acid Substitution↗
PubMed1999

Genetic linkage of autosomal-dominant Alport syndrome with leukocyte inclusions and macrothrombocytopenia (Fechtner syndrome) to chromosome 22q11-13.

Fechtner syndrome is an autosomal-dominant variant of Alport syndrome, manifested by nephritis, sensorineural hearing loss, cataract formation, macrothrombocytopenia, and polymorphonuclear inclusion bodies. As opposed to autosomal-recessive and X-linked Alport syndromes, which have been genetically well studied, the genetic basis of Fechtner syndrome remains elusive. We have mapped the disease-causing gene to the long arm of chromosome 22 in an extended Israeli family with Fechtner syndrome plus impaired liver functions and hypercholesterolemia in some individuals. Six markers from chromosome 22q yielded a LOD score >3.00. A maximum two-point LOD score of 7.02 was obtained with the marker D22S283 at a recombination fraction of 0. Recombination analysis placed the disease-causing gene in a 5.5-Mb interval between the markers D22S284 and D22S1167. No collagen genes or genes comprising the basement membrane have been mapped to this region.

Alleles↗