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Biomedical subjects

A Asherov

Publications and source records attributed to A Asherov.

10 recordsLinked to original sources
PubMed2000

Oculopharyngeal MD among Bukhara Jews is due to a founder (GCG)9 mutation in the PABP2 gene.

OBJECTIVE: To determine whether all cases of oculopharyngeal muscular dystrophy (OPMD) among Bukhara Jews share the same founder mutation. BACKGROUND: Autosomal dominant OPMD is caused by a (GCG)8-13 repeat expansion in the polyadenylation binding protein 2 (PABP2) gene. The disease has a worldwide distribution but is particularly prevalent in Bukhara Jews and in French Canadians, in whom it was introduced by three sisters in 1648. METHODS: We established the size of the PABP2 mutation in 23 Bukhara Jewish patients belonging to eight unrelated families. In all families, we constructed haplotypes for the carrying chromosomes composed of the alleles for eight chromosome 14q polymorphic markers. RESULTS: All patients share a (GCG)9 PABP2 mutation and a four-marker haplotype. Furthermore, a shared intron single nucleotide polymorphism (SNP) in the PABP2 gene 2.6Kb from the mutation was not observed in 22 families with (GCG)9 mutations from nine different countries. The smaller size of the chromosomal region in linkage disequilibrium around the mutation in Bukhara Jews, as compared with French Canadians, suggests a founder effect that occurred more than 350 years ago. Based on the Luria-Delbrück corrected "genetic clock," we estimate that the mutation appeared or was introduced once in the Bukhara Jewish population between AD 872 and 1512 (mean, AD 1243). CONCLUSION: OPMD among Bukhara Jews is the result of a shared, historically distinct, PABP2 (GCG)9 mutation that likely arose or was introduced in this population at the time they first settled in Bukhara and Samarkand during the 13th or 14th centuries.

Genetic Linkage↗
PubMed1999

Homozygotes for oculopharyngeal muscular dystrophy have a severe form of the disease.

Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) usually begins with ptosis or dysphagia during the fifth or sixth decade of life. We studied 7 patients with OPMD symptoms starting before the age of 36 years. All were found to be homozygotes for the dominant (GCG)9 OPMD mutation. On average, disease onset was 18 years earlier than in heterozygotes, and patients had a significantly larger number of muscle nuclei containing intranuclear inclusions (INIs) (9.4 vs 4.9%).

Adult↗
PubMed1998

Apolipoprotein E4 in Parkinson disease and dementia: new data and meta-analysis of published studies.

The authors examined whether the epsilon4 allele might be associated with dementia in Parkinson disease (PD), given that the dementia of PD shares neuroanatomic and neurochemical features with Alzheimer disease (AD) and that many recent studies have found a high prevalence of the epsilon4 allele of apolipoprotein E (ApoE) in AD. The authors examined patients with PD (n=125, 47 demented) and unrelated controls (n=93) using a short mental test. DNA was obtained from blood leukocytes. The relevant portion of the apolipoprotein E (ApoE) gene was amplified by polymerase chain reaction, and the epsilon4 allele was identified using a restriction enzyme. The frequency of the ApoE epsilon4 allele in demented patients with PD (14%) was not greater than that in nondemented patients (17%), whereas patients with PD as a whole showed a trend toward a higher epsilon4 allele frequency (16%) than age-matched controls (10%, p=0.07). The epsilon4 allele frequency in nondemented patients with PD was significantly higher than in controls (p=0.055). These results and the meta-analysis of four published reports fail to support the hypothesis that the epsilon4 allele is associated with dementia in PD.

Aged↗
PubMed1997

Epidemiology and inheritance of oculopharyngeal muscular dystrophy in Israel.

Oculopharyngeal muscular dystrophy (OPMD) is considered frequent among French Canadians. Our previous observations suggested it is common also among the Jews originating from Bukhara in Uzbekistan, many of whom are now living in Israel. One hundred and seventeen OPMD patients were identified in a population of 70,000 people of Bukharian descent, resulting in a calculated minimal prevalence of 1:600. In all but three families age dependent autosomal dominant inheritance was documented. There is some evidence for genetic anticipation. Three young, severely ill, patients from two different families may be homozygotes, their parents being both affected. Bukhara Jews present the second largest known cluster and the prevalence is the highest in the world. The existence of very large families, intermarriage among carriers and probably homozygote offspring may be useful for genetic studies. A 'founder effect' may explain the high prevalence of OPMD in this population.

Adult↗
PubMed1996

Esophageal smooth muscle dysfunction in oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a rare genetic disorder with late-onset progressive myopathy affecting mainly head and neck striated muscles. It is more common in certain ethnic communities. Dysphagia was usually attributed to the malfunction of striated pharyngeal muscles. We studied a group of Bukharan immigrants affected by this disorder (N = 13). Esophageal studies, including endoscopy, manometry, and scintigraphic emptying were performed. Very low pharyngeal pressures were measured. Upper esophageal pressures (UEP) were in the normal range in eight patients, and above normal in three patients. Four also had low lower esophageal sphincter pressure. Esophageal body peristaltic activity was grossly impaired in all patients: mainly nonpropulsive, simultaneous, retrograde, and failed activity was recorded. Marked retention of isotopic material was demonstrated in all patients studied, usually in the middle and lower parts of the body, ranging from 17 to 100% retention. The dysphagia in OPMD is due not only to dysfunction of pharyngeal and upper esophageal striated muscle, but also has a significant smooth muscle component.

Adult↗
PubMed1996

APOE-epsilon 4 in patients with Alzheimer disease and vascular dementia.

The apolipoprotein E (APOE) epsilon 4 allele has been consistently found to be frequent in patients with progressive degenerative dementia of the Alzheimer type (DAT). Vascular dementia (VD) may occur as strokes superimposed on presymptomatic DAT, in which case APOE-epsilon 4 frequency should also be increased in VD. We have examined the distribution of APOE-epsilon 4 in patients with DAT (n = 176) or VD (n = 74) and controls (n = 133), and evaluated the risk of dementia associated with APOE-epsilon 4. APOE-epsilon 4 allele frequency was 27% in DAT patients, 21% in VD patients, and 11% in controls. The difference in the distribution of the epsilon 4 allele between DAT or VD patients and controls was statistically significant (chi(2) test, p < 0.05), with a 3.6- and 2.1-fold risk of dementia in DAT and VD patients carrying an epsilon 4 allele. The result that the APOE-epsilon 4 allele is more frequent in DAT patients than in controls, with VD patients falling in between, is consistent with the assumption that VD is a heterogeneous condition, with some patients having an underlying preclinical brain degeneration, in whom the dementia was precipitated by strokes.

Aged↗
PubMed1996

Intranuclear inclusions in oculopharyngeal muscular dystrophy among Bukhara Jews.

We studied, by electron microscopy, muscle biopsies from seven patients with autosomal dominant oculopharyngeal muscular dystrophy (OPMD) belonging to the recently described Bukhara-Jewish cluster. Typical tubulofilamentous intranuclear inclusions (INI) of 8.5 nm outer diameter were present in all cases. The INI were observed in 4.5 +/- 1.8% of the nuclei in five patients. In the other two, they occurred in 9.5 +/- 0.5% of the nuclei and often occupied a larger nuclear area. These two patients, offspring of intermarriage between affected cousins, had an unusually severe form of OPMD beginning in their early 30s, suggesting homozygote state. Our results confirm that INI are pathognomonic for OPMD and suggest that their frequency may be quantitatively related to the number of abnormal DNA copies.

Adult↗
PubMedDate not supplied

Clinical features of oculopharyngeal muscular dystrophy among Bukhara Jews.

Oculopharyngeal muscular dystrophy (OPMD), a late onset autosomal dominant myopathy, is common among the French-Canadians and the Jews from Bukhara (Uzbekistan); most clinical histologic and genetic data published until now, as well as the recently suggested diagnostic criteria, are based on studies among the former. We studied 79 patients with OPMD belonging to the newly described Jewish-Bukhara cluster. The disease began between the ages of 21 and 78 yr (median 53 yr). In 11 patients (15%) it began before the age of 40. Ptosis was the first symptom in 59 patients and dysphagia in the remaining 20. Eight patients (10%) were monosymptomatic (ptosis) after more than 7 yr from the start of the disease; however, other family members had additional signs/symptoms. The patients belong to 29 families; in 26 age-dependent autosomal dominant inheritance could be documented. Among them there is certain evidence for genetic anticipation. This clinical study is the largest published concerning patients other than French-Canadians.

Adult↗