Anticipation (genetics)

About: Anticipation (genetics) is a research topic. Over the lifetime, 669 publications have been published within this topic receiving 21784 citations. The topic is also known as: Genetic Anticipation & Anticipation, Genetic.

Familial amyloidosis with polyneuropathy associated with TTR Ser50Arg mutation

Abstract: Background: The phenotypic heterogeneity of transthyretin amyloidosis (ATTR) familial polyneuropathy may be linked to the type of mutation and to the environmental factors. A gender difference in relation to the severity of the disease has been suspected. More than 100 different pathogenic variants of hereditary transthyretin (TTR) mutations have been reported. Objective: To describe 32 patients with confirmed TTR Ser50Arg mutation from the same geographical origin. Methods: Seven families with up to four affected generations underwent genetic testing and prospective clinical and laboratory evaluations. Results: The mutation was confirmed in seven patients from different families with clinical symptoms compatible with ATTR amyloidosis, and in 25 (62%) of the 40 direct relatives tested. Of the 32 patients with positive test results, 18 (56%) were men. Only 5 (16%) subjects were disease-free at the time of the genetic test (mean age: 20, range: 18–30-year-old). The rest developed symptoms at a young age, between ages 36 and 41. Symptomatic, histologically positive patients were older than carriers and symptomatic patients without a confirmatory biopsy. The later generation displayed symptoms at a younger age. Initial manifestations in the 27 symptomatic patients were neuropathic in 19 (70%), gastrointestinal in 6 (22%) and autonomic in 1 (4%). Significant differences were demonstrated among genders, where men had a considerably worse outcome. Conclusion: ATTR Ser50Arg mutation was associated with an early onset, an unbalanced male to female ratio, a more aggressive course in males and possibly displayed anticipation.

Megacolon complicating pregnancy. A case report.

Abstract: Megacolon is a rare complication of pregnancy. Its presence during pregnancy may require genetic counseling, anticipation of dystocia and a search for an underlying serious medical disease, the presenting symptom of which may be chronic constipation. Pharmacologic treatment is not usually successful, and the colon can best be kept clean with enemas and disimpaction.

The Anticipation and Inheritance Pattern of c.487A>G Mutation in the GJB2 Gene

Abstract: Mutations in the GJB2 gene are the most common causes of hereditary hearing loss. This study reveals some facts about the inheritance pattern of M163V in the GJB2 gene. This study was performed on two different families with non-syndromic hearing loss. We screened the GJB2 coding region with direct sequencing. There was a substitution of A to G in exon 2 at nucleotide 487 (M163V). This mutation was heterozygous in fathers and children while mothers were normal. Fathers of both families showed late onset hearing impairment, but there was early onset hearing loss in the children, which was more severe compared to the fathers. M163V has been reported as an unknown heterozygous mutation that leads to failure of the homotypic junctional channel formation. Another mutation in this codon is M163L, with an autosomal dominant inheritance, which impairs trafo cking through the plasma membrane, resulting in cell death. Assessment of the familial pedigree has revealed anticipation in phenotype and autosomal dominant inheritance. These data in addition to the high conservation of methionine residue in mammalian species suggest that M163V is inherited with an autosomal dominant pattern. Therefore, the risk of inheritance will increase. Genetic counselors and otologists should prioritize the evaluation and prevention of this disorder in patients.

Paragenetic suppressors of suppressor genes--a new class of oncodeterminants.

Abstract: Impairment or loss of suppressor genes is a common event permitting the oncogene/suppressor gene machinery to develop neoplasia. Following prenatal treatment with X-rays and UV-B, we detected a new class of oncodeterminants that could not be specified as genes. This points to paragenetic elements that suppress suppressorgenes and thus provoke melanoma at earlier ages of onset as expected, with increased severity and increased number of incidences in successive generations, in the absence of further treatment. These elements were isolated from a xiphophorine DNA library by endogenously labeled long terminal repeats (LTR) of a xiphophorine retrovirus, and were characterized as retrotransposons by Southern and Northern blotting and reverse transcription/polymerase chain reaction and transient transfection studies, in situ hybridization, and sequencing. They appear in multiple copies in the telomeric chromosome regions, where they can extend. Three open reading frames (ORF) are flanked by LTR that contain genetically active regulatory elements, and are inducible by UV-B. ORF 3 shows nests of CG dinucleotides and CGG trinucleotides, which are reminiscent of CGG nests predisposing subjects to anticipation of certain human diseases involving tumor generation. Genetic anticipation as defined by Nettleship (1909) or Warren (1996) including an increase of neoplasia might represent an acquired genetic load in preceding generations, which might provide a lead to a molecular understanding of the worldwide increase of incidences of human tumor.

Novel CAG/CTG repeat expansion mutations do not contribute to the genetic risk for most cases of bipolar disorder or schizophrenia†

Abstract: The possible presence of anticipation in bipolar affective disorder and schizophrenia has led to the hypothesis that repeat expansion mutations could contribute to the genetic etiology of these diseases. Using the repeat expansion detection (RED) assay, we have systematically examined genomic DNA from 100 unrelated probands with schizophrenia and 68 unrelated probands with bipolar affective disorder for the presence of CAG/CTG repeat expansions. Our results show that 28% of the probands with schizophrenia and 30% of probands with bipolar disorder have a CAG/CTG repeat in the expanded range, but that each expansion could be explained by one of three nonpathogenic repeat expansions known to exist in the general population. We conclude that novel CAG/CTG repeat expansions are not a common genetic risk factor for bipolar disorder or schizophrenia.