Paracentric inversion of Xq and ovarian dysfunction

We report on a paracentric inversion X(q13 q24) in a 20-year-old woman with ovarian dysfunction. The findings add evidence on the role of breakpoints in Xq13 and Xq24 in causing ovarian dysfunction. A review of the published data on paracentric inversion of chromosome X is included.     

Implicit memory for music in Alzheimer's disease

Short, unfamiliar melodies were presented to young and older adults and to Alzheimer's disease (AD) patients in an implicit and an explicit memory task. The explicit task was yes-no recognition, and the implicit task was pleasantness ratings, in which memory was shown by higher ratings for old versus new melodies (the mere exposure effect). Young adults showed retention of the melodies in both tasks. Older adults showed little explicit memory but did show the mere exposure effect. The AD patients showed neither. The authors considered and rejected several artifactual reasons for this null effect in the context of the many studies that have shown implicit memory among AD patients. As the previous studies have almost always used the visual modality for presentation, they speculate that auditory presentation, especially of nonverbal material, may be compromised in AD because of neural degeneration in auditory areas in the temporal lobes.     

The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis

Tuberous sclerosis is an autosomal dominant trait in which the dysregulation of cellular proliferation and differentiation results in the development of hamartomatous growths in many organs. The TSC2 gene is one of two genes determining tuberous sclerosis. Inactivating germline mutations of TSC2 in patients with tuberous sclerosis and somatic loss of heterozygosity at the TSC2 locus in the associated hamartomas indicate that TSC2 functions as a tumour suppressor gene and that loss of function is critical to expression of the tuberous sclerosis phenotype. The TSC2 product, tuberin, has a region of homology with the GTPase activating protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in vitro. Here we show that the region of homology between tuberin and human rap1GAP and the murine GAP mSpa1 is more extensive than previously reported and spans approximately 160 amino acid residues encoded within exons 34-38 of the TSC2 gene. Single strand conformation polymorphism analysis of these exons in 173 unrelated patients with tuberous sclerosis and direct sequencing of variant conformers together with study of additional family members enabled characterisation of disease associated mutations in 14 cases. Missense mutations, which occurred in exons 36, 37 and 38 were identified in eight cases, four of whom shared the same recurrent change P1675L. Each of the five different missense mutations identified was shown to occur de novo in at least one sporadic case of tuberous sclerosis. The high proportion of missense mutations detected in the region of the TSC2 gene encoding the GAP-related domain supports its key role in the regulation of cellular growth.      

A locus for autosomal dominant anterior polar cataract on chromosome 17p

Inherited cataract is a clinically and genetically heterogeneous disease. Here we report the identification of a new locus for an autosomal dominant anterior polar cataract on the short arm of chromosome 17. To map this new locus we performed genetic linkage analysis with microsatellite markers in a four-generation pedigree. After exclusion of seven candidate loci for cataract, we obtained significant positive LOD scores for markers D17S849 (Z = 4.01 / theta = 0.05) and D17S796 (Z = 4.17 / theta = 0.05). Multipoint analysis gave a maximum LOD score of 5.2 (theta max = 0.06) between these two markers. From haplotype analysis, the cataract locus lies in the 13 cM interval between markers D17S849 and D17S796. This study provides the first genetic mapping of an autosomal dominant anterior polar cataract.      

<Emphasis Type="Italic">TCF7L2</Emphasis>variant genotypes and type 2 diabetes risk in Brazil: significant association,but not a significant tool for risk stratification in the general population

Background  

Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.     

Ectodermal dysplasia,ectrodactyly and macular dystrophy (EEM syndrome) in siblings

We report a brother and sister with ectodermal dysplasia, ectrodactyly, and macular dystrophy (the EEM syndrome). Both children had abnormalities of the hands and the hair, and bilateral macular degeneration. The clinical picture in both is similar to, but less severe than, that described in the previously reported cases of this rare syndrome. Even though the parents are not related, they are both of Jewish Yemenite origin, and the possibility of a common ancestor cannot be ruled out. This would suggest autosomal recessive inheritance. The clinical picture in these patients suggests either variable expression or genetic heterogeneity in the EEM syndrome and further delineates the clinical and genetic spectrum of this condition. © 2001 Wiley‐Liss, Inc.     

Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type (HCHWA-D): I - A Review of Clinical, Radiologic and Genetic Aspects

Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of β-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma.
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article