Parental age effects on the occurrence of new mutations for the Marfan syndrome

Murdoch, JN; Walker, Bryan A.; McKusick, Victor A.

doi:10.1111/j.1469-1809.1957.tb01406.x

Cited by 75 publications

(14 citation statements)

References 8 publications

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“…New dominant mutations are more common in older fathers, 198 and paternal age has been shown to be associated with birth defects such as achondroplasia and Alpert syndrome 199 and in genetic conditions known to affect the cardiovascular system such as Marfan syndrome 200 ; the average age of fathers of children with sporadic or new mutation forms of Marfan syndrome was greater (37 years versus 30) than the general population. Paternal factors also have been shown to be important in diseases thought to have a combined genetic and environmental origin such as diabetes mellitus; children of a type 1 diabetic father have a greater likelihood of developing type 1 diabetes mellitus 201 than children of a mother with diabetes.…”

Section: Paternal Exposuresmentioning

confidence: 99%

Noninherited Risk Factors and Congenital Cardiovascular Defects: Current Knowledge

Jenkins¹,

Correa²,

Feinstein³

et al. 2007

Circulation

712

336

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Abstract-Prevention of congenital cardiovascular defects has been hampered by a lack of information about modifiable risk factors for abnormalities in cardiac development. Over the past decade, there have been major breakthroughs in the understanding of inherited causes of congenital heart disease, including the identification of specific genetic abnormalities for some types of malformations. Although relatively less information has been available on noninherited modifiable factors that may have an adverse effect on the fetal heart, there is a growing body of epidemiological literature on this topic. This statement summarizes the currently available literature on potential fetal exposures that might alter risk for cardiovascular defects. Information is summarized for periconceptional multivitamin or folic acid intake, which may reduce the risk of cardiac disease in the fetus, and for additional types of potential exposures that may increase the risk, including maternal illnesses, maternal therapeutic and nontherapeutic drug exposures, environmental exposures, and paternal exposures. Information is highlighted regarding definitive risk factors such as maternal rubella; phenylketonuria; pregestational diabetes; exposure to thalidomide, vitamin A cogeners, or retinoids; and indomethacin tocolysis. Caveats regarding interpretation of possible exposure-outcome relationships from case-control studies are given because this type of study has provided most of the available information. Guidelines for prospective parents that could reduce the likelihood that their child will have a major cardiac malformation are given. Issues related to pregnancy monitoring are discussed. Knowledge gaps and future sources of new information on risk factors are described.

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Section: Paternal Exposuresmentioning

confidence: 99%

Noninherited Risk Factors and Congenital Cardiovascular Defects: Current Knowledge

Jenkins¹,

Correa²,

Feinstein³

et al. 2007

Circulation

712

336

View full text Add to dashboard Cite

show abstract

“…While the changes in the skeleton and the eyes are already present at birth [1,2] cardiovascular lesions develop between the age of 10 and 20 years [6]. The autosomal dominant inheritance of Marfan's syndrome has been demonstrated in 1931 [7], spontaneous mutations may nevertheless be found in some patients [8,30].…”

Section: Introductionmentioning

confidence: 99%

Case report and study of collagen metabolism in marfan's syndrome

et al. 1981

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The case report on a 33 year old woman with prominent features of Marfan's syndrome is presented. Characteristic signs were seen in the bones, the eyes, the cardiovascular system, and the lungs. Due to regurgitation of both the aortic and mitral valves and an aneurysm of the ascending aorta a double valve replacement was made, including a prosthesis of the aorta. The problems of early diagnosis and therapy of the life-threatening cardiovascular complications are discussed. Tissue specimens from the aorta were analysed histochemically and biochemically. Histology showed a typical necrosis of the media with cyst formation. Biochemical analysis by in vitro labeling of collagen in tissue explants and by electron microscopical evaluation showed proportions of type I and type III collagen which were significantly different from controls. In both the media and the adventitia the amount of type I collagen was drastically reduced as shown by quantitation of collagen and procollagen. Fibroblasts derived from the skin of the patient showed a normal content of type I and type III collagen. It is conceivable that the reduced content of type I collagen in the aortic wall is responsible for the weakness of the vessel wall causing formation of aneurysm and its sequelae.

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“…Several autosomal dominant genetic diseases due to de novo male germ line mutations are associated with increased paternal age (18,21,45,49), suggesting that male germ line genomic stability is compromised with age. Analysis of chromosomes in spermatozoa revealed an increased frequency of aberrations with age (24,34,41,54), providing additional evidence that male germ line genomic stability decreases with age.…”

mentioning

confidence: 99%

Base Excision Repair Is Limited by Different Proteins in Male Germ Cell Nuclear Extracts Prepared from Young and Old Mice

Intano

McMahan

McCarrey

et al. 2002

Molecular and Cellular Biology

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The combined observations of elevated DNA repair gene expression, high uracil-DNA glycosylase-initiated base excision repair, and a low spontaneous mutant frequency for a lacI transgene in spermatogenic cells from young mice suggest that base excision repair activity is high in spermatogenic cell types. Notably, the spontaneous mutant frequency of the lacI transgene is greater in spermatogenic cells obtained from old mice, suggesting that germ line DNA repair activity may decline with age. A paternal age effect in spermatogenic cells is recognized for the human population as well. To determine if male germ cell base excision repair activity changes with age, uracil-DNA glycosylase-initiated base excision repair activity was measured in mixed germ cell (i.e., all spermatogenic cell types in adult testis) nuclear extracts prepared from young, middle-aged, and old mice. Base excision repair activity was also assessed in nuclear extracts from premeiotic, meiotic, and postmeiotic spermatogenic cell types obtained from young mice. Mixed germ cell nuclear extracts exhibited an age-related decrease in base excision repair activity that was restored by addition of apurinic/apyrimidinic (AP) endonuclease. Uracil-DNA glycosylase and DNA ligase were determined to be limiting in mixed germ cell nuclear extracts prepared from young animals. Base excision repair activity was only modestly elevated in pachytene spermatocytes and round spermatids relative to other spermatogenic cells. Thus, germ line shortpatch base excision repair activity appears to be relatively constant throughout spermatogenesis in young animals, limited by uracil-DNA glycosylase and DNA ligase in young animals, and limited by AP endonuclease in old animals.Germ line genomic stability is an important factor in reproductive health, with approximately 20% of genetic diseases attributed to new germ line mutations (12,13,46). Several autosomal dominant genetic diseases due to de novo male germ line mutations are associated with increased paternal age (18,21,45,49), suggesting that male germ line genomic stability is compromised with age. Analysis of chromosomes in spermatozoa revealed an increased frequency of aberrations with age (24, 34, 41, 54), providing additional evidence that male germ line genomic stability decreases with age. Similarly in mice, the spontaneous mutant frequency in a lacI transgene recovered from pachytene spermatocytes, round spermatids, and epididymal spermatozoa obtained from old animals was approximately 10-fold higher than the mutant frequency observed for young mice (60).In contrast to the decline in germ line genetic integrity with old age, the germ line DNA of young mice appears to be well maintained. Compared to somatic tissues, a lower spontaneous mutant frequency in the male germ line for a lacI transgene has been reported for fish (65), mice (32, 60), and rats (16). The murine mitotically proliferating male germ cell pool is comprised of primitive type A spermatogonia, which sequentially give rise to mitotically active, type ...

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Parental age effects on the occurrence of new mutations for the Marfan syndrome

Cited by 75 publications

References 8 publications

Noninherited Risk Factors and Congenital Cardiovascular Defects: Current Knowledge

Noninherited Risk Factors and Congenital Cardiovascular Defects: Current Knowledge

Case report and study of collagen metabolism in marfan's syndrome

Base Excision Repair Is Limited by Different Proteins in Male Germ Cell Nuclear Extracts Prepared from Young and Old Mice

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