Anticipation resulting in elimination of the myotonic dystrophy gene: a follow up study of one extended family.

Die-Smulders, C.E.M. de; Höweler, C. J.; Mirandolle, J. F.; Brunner, H. G.; Hovers, V.; Brüggenwirth, Hennie T.; Smeets, H.; Geraedts, J. P. M.

doi:10.1136/jmg.31.8.595

Cited by 14 publications

(7 citation statements)

References 24 publications

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“…Similar longitudinal studies on presymptomatic diagnosis in extended DM families have been rarely described (Barcelo ef ul.. 1993;Cobo et al, 1993;de Die-Smulders et al, 1994). The family we describe here bears a striking resemblance to the kindreds reported by Barcelo et d. (1993).…”

Section: Fig 2 Southern Blot Of Pcr Amplified Ctg Repeat Run On a supporting

confidence: 71%

Progressive expansion of the myotonic dystrophy CTG repeat in asymptomatic individuals in three successive generations of a family

Combarros

Paz

Berciano

et al. 1997

Euro J of Neurology

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We report a family in which expansion of CTG repeats was detected in asymptomatic carriers of the myotonic dystrophy allele in three successive generations. PCR-based analysis of the expanded CTG repeat revealed intergenerational amplification of the mutation. We show here that the myotonic dystrophy mutation may remain clinically silent, not only in the oldest generation of a family, but even among siblings and offspring of symptomatic cases. This may represent a mechanism for the maintenance of the myotonic dystrophy gene in the population.

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Section: Fig 2 Southern Blot Of Pcr Amplified Ctg Repeat Run On a supporting

confidence: 71%

Progressive expansion of the myotonic dystrophy CTG repeat in asymptomatic individuals in three successive generations of a family

Combarros

Paz

Berciano

et al. 1997

Euro J of Neurology

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“…Darin et al [2] estimated the point prevalence in the population under 16 years to be about 5 per 100,000. DM1 is caused by an expanded and unstable CTG repeat sequence in the 3 0 untranslated region of the DMPK gene located on the long-arm of chromosome 19. The gene's sequence belongs to the protein kinase family [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy

Douniol

Jacquette

Guilé

et al. 2009

Eur Child Adolesc Psychiatry

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Myotonic dystrophy type 1 (DM1) is the most frequent inherited neuromuscular disorder. The juvenile form has been associated with cognitive and psychiatric dysfunction, but the phenotype remains unclear. We reviewed the literature to examine the psychiatric phenotype of juvenile DM1 and performed an admixture analysis of the IQ distribution of our own patients, as we hypothesised a bimodal distribution. Two-thirds of the patients had at least one DSM-IV diagnosis, mainly attention deficit/hyperactivity disorder and anxiety disorder. Two-thirds had learning disabilities comorbid with mental retardation on one hand, but also attention deficit, low cognitive speed and visual spatial impairment on the other. IQ showed a bi-modal distribution and was associated with parental transmission. The psychiatric phenotype in juvenile DM1 is complex. We distinguished two different phenotypic subtypes: one group characterised by mental retardation, severe developmental delay and maternal transmission; and another group characterised by borderline full scale IQ, subnormal development and paternal transmission.

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“…The lower fitness of affected men compared with women, is similar to sex differences seen in other genetic disorders. Interestingly, these include several neuropsychiatric diseases caused by dynamic mutations: myotonic dystrophy (Howeler et al, 1989;de Die-Smulders et al, 1994), fragile X syndrome (Fryns, 1986;Loesch and Hay, 1988), Huntington disease in some studies (Mastromauro et al, 1989) and spinocerebellar ataxia type 1 (Jodice et al, 1994). The common mechanism for reduced fitness in these disorders appears to be low marital rates.…”

Section: Selection Effects and Sex Differencesmentioning

confidence: 99%

“…Differential expression depending on parental origin of disease genes, or imprinting, may be important in psychiatric illnesses (Flint, 1992). Imprinting has not been established to date in familial schizophrenia (Sharma et al, 1993;Asherson et al, 1994;Bassett and Honer, 1994), however sex differences in fitness may obscure the observation of imprinting effects (Howeler et al, 1989;de Die-Smulders et al, 1994). …”

Section: Introductionmentioning

confidence: 99%

Reproductive fitness in familial schizophrenia

Bassett¹,

McAlduff²,

Bury³

et al. 1995

Schizophrenia Research

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Background-Reproductive fitness is an important factor in understanding inheritance in genetic disorders. The purpose of this study was to determine whether fitness is reduced in familial schizophrenia (FS) and if fitness in siblings differs from the norm.Method-The number of offspring in 36 subjects with RDC schizophrenia or schizoaffective disorder (SZ) and their 101 siblings from large FS families was compared with age-adjusted census figures.Results-Fitness in the SZ group was significantly reduced: 23% of expected in males and 51% of expected in females. Fitness of unaffected siblings was within census expectations. However, female siblings with schizophrenia spectrum features had increased fitness over census norms. Reduced fitness was correlated with low marital rates, poor functioning and positive symptoms.Conclusions-These results indicate that reduced fitness is an important genetic force in FS and is likely inherent to the illness. Sex differences are important and would need to be considered when examining maternal and paternal transmission of schizophrenia. The results support a proposed high mutation rate for schizophrenia, consistent with a dynamic mutation mechanism.

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Anticipation resulting in elimination of the myotonic dystrophy gene: a follow up study of one extended family.

Abstract: We have re-examined an extended myotonic dystrophy (DM) family, previously described in 1955, in order to study the long term effects of anticipation in DM

Cited by 14 publications

References 24 publications

Progressive expansion of the myotonic dystrophy CTG repeat in asymptomatic individuals in three successive generations of a family

Progressive expansion of the myotonic dystrophy CTG repeat in asymptomatic individuals in three successive generations of a family

Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy

Reproductive fitness in familial schizophrenia

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