Familial transmission of chromoanagenesis leads to unpredictable unbalanced rearrangements through meiotic recombination
Julie Masson
(1)
,
Céline Pebrel-Richard
(2)
,
Matthieu Egloff
(3)
,
Mathilde Frétigny
(4)
,
Marion Beaumont
(5, 6)
,
Kevin Uguen
(7, 8, 9)
,
Pierre‐antoine Rollat-Farnier
(5)
,
Flavie Diguet
(5)
,
Isabelle Perthus
(10)
,
Gwenaël Le Gudayer
(3)
,
Damien Haye
(5)
,
Marie‐noëlle Bonnet Dupeyron
(5, 11)
,
Audrey Putoux
(12)
,
Fabienne Raskin-Champion
(13)
,
Marianne Till
(5)
,
Nicolas Chatron
(5, 14)
,
Bérénice Doray
(15, 16)
,
Claire Bardel
(17, 18, 19)
,
Christine Vinciguerra
(20, 21)
,
Damien Sanlaville
(5, 14)
,
Caroline Schluth-Bolard
(5, 14, 15)
1
PPrime [Poitiers] -
Institut Pprime [UPR 3346]
2 Service Cytogénétique Médicale [CHU Clermont-Ferrand]
3 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
4 Service de Chirurgie Gynécologique Oncologique et Obstétrique [CHU Lyon Sud]
5 GHE - Groupement Hospitalier Lyon-Est
6 Clinique Pierre-Cherest - Laboratoire Eylau-Unilabs [Neuilly-sur-Seine ]
7 GGB - Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
8 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
9 EFS
10 CHU Clermont-Ferrand
11 CH DE VALENCE - Centre Hospitalier de Valence
12 HCL - Hospices Civils de Lyon
13 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
14 INMG - Institut NeuroMyoGène
15 HUS - Les Hôpitaux Universitaires de Strasbourg
16 Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion]
17 Biostatistiques santé [LBBE]
18 Service de Biostatistiques [Lyon]
19 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
20 CBPE - Centre de Biologie et Pathologie Est [Bron]
21 UCBL ISPB - Université Claude Bernard Lyon 1 - Institut des Sciences Pharmaceutiques et Biologiques
2 Service Cytogénétique Médicale [CHU Clermont-Ferrand]
3 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
4 Service de Chirurgie Gynécologique Oncologique et Obstétrique [CHU Lyon Sud]
5 GHE - Groupement Hospitalier Lyon-Est
6 Clinique Pierre-Cherest - Laboratoire Eylau-Unilabs [Neuilly-sur-Seine ]
7 GGB - Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
8 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
9 EFS
10 CHU Clermont-Ferrand
11 CH DE VALENCE - Centre Hospitalier de Valence
12 HCL - Hospices Civils de Lyon
13 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
14 INMG - Institut NeuroMyoGène
15 HUS - Les Hôpitaux Universitaires de Strasbourg
16 Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion]
17 Biostatistiques santé [LBBE]
18 Service de Biostatistiques [Lyon]
19 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
20 CBPE - Centre de Biologie et Pathologie Est [Bron]
21 UCBL ISPB - Université Claude Bernard Lyon 1 - Institut des Sciences Pharmaceutiques et Biologiques
Matthieu Egloff
- Fonction : Auteur
- PersonId : 1359502
- ORCID : 0000-0002-3146-1622
- IdRef : 220113645
Kevin Uguen
- Fonction : Auteur
- PersonId : 1104746
- ORCID : 0000-0002-6744-2837
- IdRef : 269226087
Nicolas Chatron
- Fonction : Auteur
- PersonId : 1181600
- ORCID : 0000-0003-0538-0981
Claire Bardel
- Fonction : Auteur
- PersonId : 21685
- IdHAL : claire-bardel
- IdRef : 110530179
Caroline Schluth-Bolard
- Fonction : Auteur
- PersonId : 774839
- ORCID : 0000-0002-2279-4273
- IdRef : 099490145
Résumé
Abstract Chromoanagenesis is a cellular mechanism that leads to complex chromosomal rearrangements (CCR) during a single catastrophic event. It may result in loss and/or gain of genetic material and may be responsible for various phenotypes. These rearrangements are usually sporadic. However, some familial cases have been reported. Here, we studied six families in whom an asymptomatic or paucisymptomatic parent transmitted a CCR to its offspring in an unbalanced manner. The rearrangements were characterized by karyotyping, fluorescent in situ hybridization, chromosomal microarray (CMA) and/or whole genome sequencing (WGS) in the carrier parents and offspring. We then hypothesized meiosis‐pairing figures between normal and abnormal parental chromosomes that may have led to the formation of new unbalanced rearrangements through meiotic recombination. Our work indicates that chromoanagenesis might be associated with a normal phenotype and normal fertility, even in males, and that WGS may be the only way to identify these events when there is no imbalance. Subsequently, the CCR can be transmitted to the next generation in an unbalanced and unpredictable manner following meiotic recombination. Thereby, prenatal diagnosis using CMA should be proposed to these families to detect any pathogenic imbalances in the offspring.