Prenatal diagnosis of Duchenne and Becker muscular dystrophies: Underestimated problem of the secondary prevention of monogenetic disorders

Massalska, Diana; Zimowski, Janusz; Roszkowski, Tomasz; Bijok, Julia; Pawelec, Magdalena; Bednarska-Makaruk, Małgorzata

doi:10.1111/jog.13344

Cited by 2 publications

(1 citation statement)

References 30 publications

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“…However, experience shows that in the Netherlands, for example, 78% of girls over 16 years of age have not yet been tested, and the probable cause is that the average age of motherhood is about 28 years of age, so they are tested later [29], while 1/3 of potential carriers are not tested at all [30]. It has been found that only 52.7% of women at risk for DMD/BMD were tested for carrier status before conception [31]. It should be kept in mind that, in addition to the risk of bearing affected offspring, 10% of female carriers develop cardiomyopathy [32,33], so early detection of carrier status would allow adequate cardiac monitoring of these women, which is recommended from the age of 16 [34].…”

Section: Discussionmentioning

confidence: 99%

The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies

et al. 2023

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Background/Aim. Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. They are X-linked recessive diseases, where males are affected and females are mostly healthy carriers of the mutation. It is estimated that 2/3 mothers of DMD probands are carriers, while 1/3 of patients have de novo mutations. The aim was to confirm the carrier status of females in the families of DMD/BMD probands, using direct genetic methods. Methods. We tested 38 females from 31 families of DMD/BMD probands with deletion/duplication in the dystrophin gene. Also, 4 cases of prenatal diagnosis of DMD/BMD were included. We preformed the polymerase chain reaction (PCR) and the multiplex ligation-dependent method (MLPA) for deletion detection, i.e. deletion/duplication in the dystrophin gene. Results. In 31 DMD/BMD probands, we identified 87.1% deletions and 12.9% duplications of one or more exons. Of the 29 tested mothers, mutations were found in 17 (14 deletions and 3 duplications). Mutations were found in 57.9% (11/19) mothers of DMD and in 60% (6/10) mothers of BMD, respectively. Also, in probands with deletions 56% (14/25) of mothers were carries and in probands with duplications 3 mothers of 4 (75%). Of the 9 other female relatives, mutations were found in 4. In prenatal diagnosis, we identified deletion in one male and one female foetus of one mother. Conclusion. The study showed that mothers were carriers in almost 60% of sporadic cases of DMD/BMD with deletions and duplication. Also, the carrier frequency tended to be higher in mothers of the probands with duplication (75%) then in probands with deletions (56%). In the case of a mother who was confirmed as a carrier, deletion was detected in 2 of 3 foetuses.

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Section: Discussionmentioning

confidence: 99%

The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies

et al. 2023

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A retrospective cohort study and review of the literature about germline mosaicism in Duchenne/Becker muscular dystrophy prenatal counseling: How to estimate the recurrence risk in clinical settings?

Verebi,

Gravrand,

Bienvenu

et al. 2024

Journal of Genetic Counseling

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Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are the most common inherited neuromuscular diseases. Following the identification of a pathogenic causative variant in the DMD gene of a proband, potential carriers can be informed of their risk of having offspring with the disease. Germline mosaicism is a variant that is confined to the gonads that can be transmitted to offspring and is usually reported when a non‐carrier of a DMD pathogenic variant has two or more offspring carrying the variant in question. On average, one third of cases are the result of a de novo variant, and as DMD and BMD are prone to germline mosaicism, its inclusion in genetic counseling is mandatory. In this retrospective cohort study, we presented clinical data from an unpublished DMD/BMD cohort of 332 families with incidence of germline mosaicism in families with de novo transmission of 8.1%. This is also the first systematic literature review searching PubMed to provide an accurate assessment of the current literature on germline mosaicism in DMD and BMD, including 17 case reports and 20 original studies. The incidence of documented germline mosaicism in de novo event families ranged from 6.0 to 40%, with a mean of 8.3%. The estimated recurrence risk for mothers of a patient with a proven de novo causal variant ranged from 4.3 to 11%, with a mean of 5.8% for a male fetus. By providing an up‐to‐date and comprehensive overview of the literature, this review aims to improve our understanding of germline mosaicism in DMD and to promote the development of effective strategies and reliable data for occurrence risk assessment in genetic counseling of de novo event families.

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Prenatal diagnosis of Duchenne and Becker muscular dystrophies: Underestimated problem of the secondary prevention of monogenetic disorders

Cited by 2 publications

References 30 publications

The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies

The importance of direct genetic testing for determining female carriers of the mutation in dystrophinopathies

A retrospective cohort study and review of the literature about germline mosaicism in Duchenne/Becker muscular dystrophy prenatal counseling: How to estimate the recurrence risk in clinical settings?

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