Anticipation in Huntington's disease is inherited through the male line but may originate in the female.

Ridley, R. M.; Frith, C. D.; Crow, T. J.; Conneally, P. Michael

doi:10.1136/jmg.25.9.589

Cited by 142 publications

(79 citation statements)

References 18 publications

(6 reference statements)

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“…Data from the family investigations (Tables 3 and 4) revealed a trend of decrease in age at diagnosis in successive generations. These observations, taken together, suggest an onset and progression pattern of the disease that is compatible with the concept of anticipation that describes youngeronset and/or more severe symptom(s) in successive generations of a disease with genetic susceptibility (13)(14)(15). At the molecular level, anticipation may be associated with genomic instability, such as trinucleotide repeat expansions (13,14).…”

Section: Discussionsupporting

confidence: 73%

“…At the molecular level, anticipation may be associated with genomic instability, such as trinucleotide repeat expansions (13,14). In Huntington's disease, anticipation may be inherited through the male line (15). In this respect, it is interesting that we have observed a paternal effect on the development of type 2 diabetes in this Chinese population (5).…”

Section: Discussionmentioning

confidence: 79%

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Factors Predicting the Age When Type 2 Diabetes Is Diagnosed in Hong Kong Chinese Subjects

Lee

et al. 2001

Diabetes Care

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OBJECTIVE -To examine the factors predicting age at diagnosis of type 2 diabetes in Hong Kong Chinese. RESEARCH DESIGN AND METHODS -The relationships between age at diagnosis and parental history of diabetes as well as an array of clinical and metabolic factors were examined using a hospital clinic-based diabetes registry involving 3,414 index patients with type 2 diabetes. Patterns of age at diagnosis in successive generations were also examined using 21 affected child-parent pairs and 7 affected child-parent-grandparent trios.RESULTS -Approximately 29% of the index patients were diagnosed with type 2 diabetes at Յ35 years of age (hereby defined as early-onset). Compared with the patients diagnosed at Ͼ35 years of age (hereby defined as late-onset), the early-onset patients had higher rates of positive paternal (16 vs. 5%) and maternal (22 vs. 12%) history of diabetes (both at P Ͻ 0.01) and had poorer metabolic profiles. In the overall index patients, male sex, higher HbA 1c , waist-to-hip ratio (WHR), and systolic blood pressure (sBP); lower HDL cholesterol level; and a positive paternal as well as maternal history of diabetes predicted younger age at diagnosis. More senior age and higher BMI and diastolic blood pressure predicted older age at diagnosis. Predictors for younger age at diagnosis in the male patients were higher HbA 1c and sBP and a positive paternal history of diabetes. Predictors for younger age at diagnosis in the female patients were higher HbA 1c , WHR, and sBP and a paternal as well as maternal history of diabetes. In the affected child-parent pairs and child-parent-grandparent trios, there was a decrease in age at diagnosis in successive generations.CONCLUSIONS -Our data indicate that both familial (possibly genetic) and metabolic factors affect the age of onset of type 2 diabetes in the Chinese population. The results also suggest an onset and progression pattern of the disease that is compatible with the phenomenon of anticipation. Diabetes Care 24:646 -649, 2001T ype 2 diabetes is one of the major noncommunicable diseases worldwide, and its complications have significant socioeconomic impacts. Classically, type 2 diabetes develops predominantly in older populations. However, there is increasing evidence for a high prevalence of type 2 diabetes in young people, particularly in non-Caucasians (1). Early onset of type 2 diabetes appears to be heterogeneous in etiologies. Maturity-onset diabetes of the young (MODY) is a monogenic disease inherited in an autosomal dominant manner, whereas autoimmune diabetes may have atypical presentations (2,3). In Hong Kong Chinese, MODY, typical type 1 diabetes, and atypical autoimmune diabetes do occur, but they only account for a small proportion of the overall type 2 diabetic population (2-4). In a recent segregation study involving 2,310 index patients, we observed the evidence for familial clustering, maternal influence, a male sexspecific paternal effect, and an association between younger age at diagnosis and a positive parental history of diabetes...

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 79%

Factors Predicting the Age When Type 2 Diabetes Is Diagnosed in Hong Kong Chinese Subjects

Lee

et al. 2001

Diabetes Care

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“…2). Among all the family members, III 10 , III 12 , III 14 , IV 3 , IV 11 , IV 12 , IV 14 , and V 2 carried the abnormal alleles of more than 240 bp. Pathogenic IT15 gene was not found in all the other individuals at risk, including the pregnant female member.…”

Section: Analysis Of the Pcr Productsmentioning

confidence: 99%

“…The total 25 L of PCR system contained 3 μL of 30 μg/mL genomic DNA, 4 μL of 2.5 mmol/L dNTP, 2 μL of 10 μmol/L primers, 12.5 μL of 2 × GC buffer (Takara, Japan) (or, 2.5 μL of 10 × buffer and 1.25 μL DMSO), 0. 14 , and IV 12 were HD patients with the classical symptoms, including choreic movements, decreased cognitive abilities, and psychological impairments. IV 11 showed unsteady gait and limp, and IV 14 demonstrated apparently frequent eye movement, which was suspected to be an early HD symptom.…”

Section: Pcr Amplificationmentioning

confidence: 99%

Intergeneration CAG expansion in a Wuhan juvenile-onset Huntington disease family

Liu

Shen

et al. 2007

Neurosci. Bull.

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Objective To make early diagnosis of IT15 gene mutation in a Wuhan juvenile-onset Huntington disease (HD) family, for providing them with genetic counseling, and making preparation for the further research on pathogenesis and experimental therapy of HD. Methods According to the principle of informed consent, we extracted genomic DNA from peripheral blood samples and carried genetic diagnosis of pathogenic exon 1 of IT15 gene by modified touchdown PCR and DNA sequencing methods. Results Eight of twenty-five family members carried abnormal allele: III 10 , III 12 , III 14 , IV 3 , and V 2 carried (CAG) 48 , IV 11 and IV 12 carried (CAG) 67 , and IV 14 carried (CAG) 63 , in contrast with the 8-25 CAG trinucleotides in the members of control group. IV 14 carried 15 more CAG trinucleotides than her father III 10 . Conclusion The results definitely confirm the diagnosis of HD and indicate the CAG trinucleotide repeat expansion of IT15 gene in this HD family. In addition, CAG expansion results in juvenile-onset and anticipation (characterized by earlier age of onset and increasing severity) of the patient IV 12 .

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“…However, since the late 1980s, new evidence of epidemiological anticipation in several neuromuscular and neurological diseases has been reported, even after ascertainment biases were excluded (Ridley et al 1988;Höweler et al 1989), and these lines of evidence were soon followed by evidence of biological anticipation that showed a correlation between decrease in AO and increase in severity with the presence of TRE. These findings provide not only a new understanding of the molecular-genetic basis of anticipation in those diseases but also suggest a reconsideration of the involvement of anticipation in psychiatric disorders.…”

Section: Introductionmentioning

confidence: 99%

Anticipation in Japanese families with schizophrenia

et al. 1998

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The identification of anticipation in schizophrenia is a recent focus in the genetic epidemiology of schizophrenia, although it involves some controversial methodological issues. We explored the evidence of anticipation among 44 Japanese two-generation pairs with schizophrenia found by reviewing nine years of admission records (1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994) at the Department of Neuropsychiatry, Nagasaki University Hospital and Michino-o Hospital, Nagasaki. The 44 pairs consisted of 27 two-generation pairs of first-degree relatives group (FDRG) and 17 pairs of second-degree relatives group (SDRG). On pairwise comparison and a life table analysis, the age at onset (AO) was significantly earlier in the lower generation (G2) than in the upper generation (G1) in all of the pairs and in the two subgroups, FDRG and SDRG. Earlier AO was shown in G2 even after minimizing some statistical biases for the study of anticipation in schizophrenia. A significant earlier mean AO was found in G2 even when a cohort effect was controlled for. There was no marked difference in AO between paternal and maternal transmission. These results provide further evidence for epidemiological anticipation, suggesting biological anticipation such as the involvement of trinucleotide repeats expansion in G2. The limitations of the study are also discussed.

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Anticipation in Huntington's disease is inherited through the male line but may originate in the female.

Cited by 142 publications

References 18 publications

Factors Predicting the Age When Type 2 Diabetes Is Diagnosed in Hong Kong Chinese Subjects

Factors Predicting the Age When Type 2 Diabetes Is Diagnosed in Hong Kong Chinese Subjects

Intergeneration CAG expansion in a Wuhan juvenile-onset Huntington disease family

Anticipation in Japanese families with schizophrenia

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