Familial occurrence of neonatal diabetes with duplications in chromosome 6q24: treatment with sulfonylurea and 40-yr follow-up

We present a Norwegian family, followed since 1967, with a chromosome 6q24 duplication in two siblings with neonatal diabetes, in their non-diabetic father, and in a female (third generation) with adult-onset diabetes. The parents (first generation) were healthy and non-consanguineous. After a miscarriage, the couple had two infants with birth weights of 1780 and 1620 g, respectively, both of whom died on their second day of life. Patient I (male, weight 1840 g at term) had a blood glucose level of 33 mmol/L on day 6. He was treated with insulin for 3 months. In adult life he had permanent diabetes, treated with oral hypoglycemic agents. At 43 yr of age, there were no diabetic late complications. Patient II (female, birth weight 1440 g at term) had an increasing blood glucose of 55 mmol/L on day 13. She received insulin treatment for 12.5 months. Subsequently, she was successfully treated with sulfonylurea (tolbutamide) for 10 yr. At 11 yr of age, insulin was again considered necessary. At 40 yr of age, no diabetic late complications were detected. Patient III had a birth weight of 2630 g at term and no diabetic symptoms as a neonate. She had insulin-requiring diabetes from age 19. We conclude that (i) neonatal diabetes with chromosome 6q24 duplications may become a permanent disease in adult life; (ii) this chromosome anomaly may also be associated with adult-onset diabetes; (iii) sulfonylurea treatment may be attempted, and (iv) late diabetic complications may be absent, even after more than 40 yr.     

Cytogenetic and comparative genomic hybridization studies of an esophageal giant fibrovascular polyp: a case report

Esophageal giant fibrovascular polyps are rare and are thought to represent redundant tumorlike or hamartomatous esophageal folds. Although most patients present with slowly evolving dysphagia, a minority present with acute respiratory distress or even death caused by asphyxia. We present the pathologic and cytogenetic findings of an 18-cm esophageal giant fibrovascular polyp in a 49-year-old woman who presented with odynophagia and dysphagia. The histologic findings are that of classic esophageal giant fibrovascular polyp as previously described in the literature. Cytogenetic study revealed an abnormal karyotype, and comparative genomic hybridization analysis showed regional amplifications of chromosomes 3 and 12 and a possible loss of 22q13.3-qter. The significance of these cytogenetic findings is unclear but may suggest a neoplastic process in the pathogenesis of esophageal giant fibrovascular polyps.     

Microchimerism in labial salivary glands of hematopoietic stem cell transplanted patients

Oral Diseases (2011) 17 , 484–488 Objective: Microchimerism has been extensively investigated in autoimmune diseases, which display similarities with graft‐vs‐host disease. This study was conducted to investigate the presence of microchimerism in minor salivary glands of hematopoietic stem cell transplanted patients, one of the targets of graft‐vs‐host disease. Methods: Labial salivary glands biopsy specimens from 11 stem cell transplanted patients were analysed. The samples were grouped in control (five specimens from a female‐to‐female transplantation) and study group (five glands from male‐to‐female transplantation). One male transplanted patient was used as a positive control. Fluorescence in situ hybridization with Y‐chromosome probe and immunofluorescence with anticytokeratin AE1/AE3 and CD45 were used to identify Y‐chromosome positive glandular epithelial cells from allogeneic hematopoietic stem cell transplanted patients. Results: In the study group, all samples were positive to Y‐chromosome and cytokeratin AE1/AE3, in agreement with the pattern exhibited by male labial salivary gland. None of the samples from control group were positive to Y‐chromosome despite being positive to cytokeratin AE1/AE3. Positivity to CD45 was not relevant. Conclusion: Microchimerism in the labial salivary glands of sex‐mismatched stem cell transplanted patients is a real phenomenon. Further studies are necessary to elucidate the impact of this phenomenon on the clinical status of stem cell transplanted patients.     

Autosomal dominant cornea plana: Clinical findings in a Cuban family and a review of the literature

Cornea plana may occur in connection with malformations of the eye or of other parts of the body. As an isolated ocular anomaly, it may be inherited in an autosomal recessive or in an autosomal dominant fashion. We have previously mapped genes for both forms of the disease to 12q21.

We studied 36 members of three generations of a Black Cuban family with autosomal dominant cornea plana. Three affected males and 11 affected females were examined. Corneal refraction varied between 37.50 and 42.75 diopters. Horizontal corneal diameter ranged from 8.75 to 11.25 mm. The cornea was clear and the limbal zone only occasionally widened. A marked arcus senilis was present in six patients aged 30 to 58 years, but in none of their healthy relatives. The anterior chamber was shallow in those affected, varying in depth from 1.68 to 2.38 mm. One woman was blind from closed-angle glaucoma. The axial length was within normal limits in all patients.     

Karl Lisch,MD: Remembered July 24, 1907 - February 5, 1999

Purpose: To report a novel VMD2 gene mutation in a Japanese family with Best disease and the clinical phenotype of the patients. Patients and methods: Mutational analysis for VMD2 was performed by direct sequencing in two members of a Japanese family with Best disease. Clinical examination included visual acuity, electro-oculography (EOG), and fundus examination. Results: A T990C mutation of the VMD2 gene was found in the 20-year-old boy and his 47-year-old mother. The boy had bilateral vitelliform cyst-like lesions in both eyes and showed a pathological Arden ratio of 1.0 on EOG. The mother had a normal fundus appearance with an Arden ratio of 1.0 on EOG. Conclusion: A novel disease-causing mutation in the VMD2 gene (T990C) was found in Japanese patients with Best disease.     

Y染色体变异与男性不育

男性不育是一种常见的复杂疾病,Y染色体连锁生精障碍是该病的一个重要病因.Y染色体男性特异性区域存在大量的重复序列,这些序列间频发的染色体内非等位性同源重组,使Y染色体具备了高变异率的特点,这些结构变化较易引起生精相关基因的剂量改变,进而导致男性不育.作者对近年来DNA水平上男性不育相关的Y染色体变异研究进行了综述.     

Global gene profiling and comprehensive bioinformatics analysis of a 46,XY female with pericentric inversion of the Y chromosome

XY females are rare individuals who carry a Y chromosome but are phenotypically female. In approximately 80–90% of these cases, there are no mutations in the SRY gene, a testis-determining gene on the short arm of the Y chromosome, and the pathophysiology of XY females without SRY mutation remains unclear. In the present study, we used a molecular data mining technique to analyze the pathophysiology of an XY female with functional SRY and pericentric inversion of the Y chromosome, and compared the results with those of a normal male. Interestingly, upregulations of numerous genes included in the development category of the Biological Process ontology, including genes associated with sex determination and organ morphogenesis, were seen in the patient. Additionally, the transforming growth factor-β (TGF-β) signaling pathway and Wnt signaling pathway, in which most cell–cell interactions during embryonic development are involved, were altered. Alterations in the expression of numerous genes at the developmental stage, including alterations at both the gene and pathway levels, may persist as a vestige of anomalies of sex differentiation that presumably began in the fetal period. The present study indicates that a data mining technique using bioinformatics contributes to identification of not only genes responsible for birth defects, but also disorders of sex development (DSD)-specific pathways, and that this kind of analysis is an important tool for clarifying the pathophysiology of human idiopathic XY gonadal dysgenesis. Our findings could serve as one of the basic datasets which will be used for future follow-up investigations.     

Gain of chromosome X in prostatic atrophy detected by CGH and FISH analyses

BACKGROUND: Focal atrophy is presumed to be an indirect forerunner of prostate cancer. The aim of this study was to examine genetic alterations in prostate epithelia deriving from atrophic areas and compare these findings with those of cells deriving from paired prostate cancer in the same patient. METHODS: Formalin fixed paraffin wax-embedded prostatectomy specimens from 20 prostate cancer patients were utilized in this study. Comparative Genomic Hybridization (CGH) was performed on atrophic areas. To validate the CGH results, Fluorescence in Situ Hybridization (FISH) analysis was performed on atrophic areas and paired cancer tissue. RESULTS: Gain of the whole chromosome X was found as sole aberration in seven (70%) atrophic tissues by CGH. A gain of centromere X was observed in 13 (68.4%) atrophic areas and in 18 (90%) cancer tissues using FISH. CONCLUSIONS: Our investigation reconfirms the genetical instability of cells of the atrophic acini and attention of relevance of gain of chromosome X in atrophic areas.