Biomedical subjects
Publications and source records attributed to Laila Zahed.
Approximately 40 patients with terminal duplication of the distal short arm of chromosome 7 have been reported, the smallest being dup(7)(p21). We report here on a patient with a smaller duplication, dup(7)(p22.1), detected on G-banding and characterized by array-CGH. We establish phenotype-karyotype correlations with the reported patients with other 7p duplications.
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Premature ovarian failure (POF) is characterized by elevated gonadotropins and amenorrhea in women aged <40 years. In a Lebanese family with five sisters who received the diagnosis of POF, we established linkage to the long arm of the X chromosome (between Xq21.1 and Xq21.3.3), using whole-genome SNP typing and homozygosity-by-descent mapping. By sequencing one candidate gene within that region, POF1B, we identified a point mutation localized in exon 10. This substitution of a nucleotide (G-->A), at position 1123, results in an arginine-->glutamine mutation of the protein sequence at position 329 (mutation R329Q). All the affected family members were homozygous for the mutation, whereas the unaffected members were heterozygous. Because POF1B shares high homology with the tail portion of the human myosin, we assessed the ability of both wild-type and mutant POF1B proteins to bind nonmuscle actin filaments in vitro. We found that the capacity of the mutant protein to bind nonmuscle actin filaments was diminished fourfold compared with the wild type, suggesting a function of POF1B in germ-cell division. Our study suggests that a homozygous point mutation in POF1B influences the pathogenesis of POF by altering POF1B binding to nonmuscle actin filaments.
CONTEXT: Parathyroidectomy is the only effective therapy for osteitis fibrosa cystica in hyperparathyroidism. OBJECTIVE: The objective of this study was to describe the changes of skeletal and nonskeletal manifestations in a patient with hyperparathyroidism and renal failure after oral vitamin D therapy. DESIGN: This was a descriptive case report. SETTING: The patient was followed up in a referral center. PATIENT: A 55-yr-old male patient with moderate renal failure was referred for expansile lytic lesions affecting several ribs and the spinous process of T12. His creatinine was 1.8 mg/dl; calcium, 8.9 mg/dl; PTH, 666 pg/ml; and 1,25 dihydroxy-vitamin D, 27 pg/ml. Bone mineral density (BMD) Z-scores by dual-energy x-ray absorptiometry were -4.1 at the spine, -1.7 at the hip, and -4.3 at the forearm. MAIN OUTCOME MEASURES: The main outcome measures were the skeletal manifestations of hyperparathyroidism. RESULTS: At 10 months of therapy, calcium level was 10 mg/d, PTH level declined to 71 pg/ml, and BMD increased by 12% at the spine and 18% at the hip. Computerized tomography (CT) cuts revealed marked regression in the lytic lesions. At 2 yr, BMD increased by an additional 6% at the spine, and there were no further changes in the lytic lesions by CT. The vitamin D receptor genotype using the restriction enzymes Bsm1, Taq1, and Apa1 was Bb, tt, and AA. CONCLUSIONS: We showed regression of severe skeletal abnormalities of hyperparathyroidism documented by serial CT images in response to oral vitamin D therapy. It is possible that the vitamin D receptor genotype of the patient modulated this response.
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Oculocutaneous albinism type 1 (OCA1) results from mutations in the tyrosinase gene, which lead to partial or complete loss of activity of the corresponding enzyme. A large number of mutations have been identified worldwide, providing insight into the pathogenesis of the disorder. We performed ophthalmic and dermatological exams on 30 Lebanese subjects with oculocutaneous albinism, then screened for mutations in the tyrosinase gene in an effort to establish the molecular basis of the disorder in our population and correlate it with phenotypic findings. The five exons of the gene together with the exon-intron boundaries and part of the promoter region were sequenced. Mutations were found in a total of 14 patients (47%) while no mutation was identified in the sequenced regions in 53% of patients. Fourteen different mutations were identified of which eight were novel while six had been previously reported. Mutations were mainly seen in patients with clinical findings, suggestive of OCA1A (64% of patients with OCA1A versus 25% of patients with OCA1B); therefore, the absence of mutations in some of the other patients may indicate the involvement of other genes.
The Arab countries encompass a wide region stretching from the Persian Gulf to the Atlantic Ocean. The Arab population is quite heterogeneous and has experienced various invasions and migrations throughout history. beta-thalassemia is endemic in all countries of the Arab world. Our review of the molecular basis of beta-thalassemia in various Arab countries reveals the presence of 52 mutations, which are mostly of Mediterranean and Asian origin. The distribution of mutations reflects the geographical and historical backgrounds of each region. However, no specific mutation is confined to the Arabs, although some Arab countries do have unique mutations.
BACKGROUND: Patients with thalassemia may complain of numbness and weakness of the lower extremities. The aim of the study was to document whether these patients suffer from a polyneuropathy and to determine any contributing factors for the development of neuropathy. PATIENTS AND METHODS: We examined 30 patients with thalassemia major and intermedia, clinically and electrophysiologically. We correlated these findings with demographics, blood status, and treatment and compared electrophysiologic data with 30 age- and sex-matched normal subjects or historical controls. RESULTS: We found that 78% of thalassemic patients suffered from a mild sensory polyneuropathy. The neuropathy seemed to be worse in the intermedia type. Thalassemic patients who received blood transfusions and deferoxamine had better nerve function than those who did not, irrespective of the dose of deferoxamine. The neuropathy was worse for older patients, irrespective of sex. The hemoglobin level, and the fact that some patients underwent splenectomy, did not affect the status of the patients' nerves. CONCLUSION: Patients with thalassemia may suffer from a sensory polyneuropathy especially as they grow older and if they are not optimally treated.