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.

Letter regarding "An attempt to throw light on congenital hip disease terminology and anticipation of clinical outcomes when treated with total hip arthroplasty", by Hartofilakidis G et al.

Abstract: Dear Editor, We read the article by G. Hartofilakidis and colleagues with great interest. In their publication, the authors underline the importance of understanding the difference between 3 types of congenital hip disease. Correct interpretation of this classification can help in the acceptance of a solution for some challenging situations. Unfortunately, however, morphological and radiographic images are so widely used that these have been described in the popular Hartofilakidis classification. Type A (dysplasia): “The femoral head is contained within the original acetabulum despite the degree of subluxation.” In adults, the border between the original acetabulum and the superior osteophyte is difficult to find. The same is true for the inferior osteophyte of the femoral head. We think that type A needs elaboration regarding the femoral head position. Type B (low dislocation): “The femoral head articulates with a false acetabulum that partially covers the true acetabulum to varying degrees.” Letter regarding “An attempt to throw light on congenital hip disease terminology and anticipation of clinical outcomes when treated with total hip arthroplasty”, by Hartofilakidis G et al

Anticipation Can Be More Common in Hereditary Spastic Paraplegia with SPAST Mutations Than It Appears.

Abstract: BACKGROUND AND OBJECTIVE Hereditary spastic paraplegia (HSP) is a heterogeneous neurodegenerative disorder with lower-limb spasticity and weakness. Different patterns of inheritance have been identified in HSP. Most autosomal-dominant HSPs (AD-HSPs) are associated with mutations of the SPAST gene (SPG4), leading to a pure form of HSP with variable age-at-onset (AAO). Anticipation, an earlier onset of disease, as well as aggravation of symptoms in successive generations, may be correlated to SPG4. Herein, we suggested that anticipation might be a relatively common finding in SPG4 families. METHODS Whole-exome sequencing was done on DNA of 14 unrelated Iranian AD-HSP probands. Data were analyzed, and candidate variants were PCR-amplified and sequenced by the Sanger method, subsequently checked in family members to co-segregation analysis. Multiplex ligation-dependent probe amplification (MLPA) was done for seven probands. Clinical features of the probands were recorded, and the probable anticipation was checked in these families. Other previous reported SPG4 families were investigated to anticipation. RESULTS Our findings showed that SPG4 was the common subtype of HSP; three families carried variants in the KIF5A, ATL1, and MFN2 genes, while five families harbored mutations in the SPAST gene. Clinical features of only SPG4 families indicated decreasing AAO in affected individuals of the successive generations, and this difference was significant (p-value <0.05). CONCLUSION It seems SPAST will be the first candidate gene in families that manifests a pure form of AD-HSP and anticipation. Therefore, it may be a powerful situation of genotype-phenotype correlation. However, the underlying mechanism of anticipation in these families is not clear yet.

Does genetic anticipation occur in familial Alexander disease

Abstract: Alexander Disease (AxD) is a rare leukodystrophy caused by missense mutations of glial fibrillary acidic protein (GFAP). Primarily seen in infants and juveniles, it can present in adulthood. We report a family with inherited AxD in which the mother presented with symptoms many years after her daughter. We reviewed the age of onset in all published cases of familial AxD and found that 32 of 34 instances of parent-offspring pairs demonstrated an earlier age of onset in offspring compared to the parent. We suggest that genetic anticipation occurs in familial AxD and speculate that genetic mosaicism could explain this phenomenon.

Triplet Repeat Disorders

Abstract: Triplet repeat disorders are a category of disease caused by the lengthening of repetitive DNA sequence elements in particular genes. These unusual sequences, while normal in certain lengths, are prone to errors during DNA replication that result in their expansion. At some threshold length, the expansion causes disease, either by altering the structure of the protein (when the expansions are in coding regions) or by disrupting some unknown regulatory process (when the expansions are outside coding regions). Although the genes involved in these disorders are widely expressed throughout the body, symptoms are usually confined to the nervous system (Huntington's disease and Fragile X) or muscles (myotonic dystrophy).