De novo variants and recombination at 4q35: Hints for preimplantation genetic testing in facioscapulohumeral muscular dystrophy.

Autor: Pini S; Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy., Napoli FM; Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy., Tagliafico E; Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, Azienda Ospedaliero Universitaria Policlinico, Modena, Italy., La Marca A; Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, Azienda Ospedaliero Universitaria Policlinico, Modena, Italy., Bertucci E; Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, Azienda Ospedaliero Universitaria Policlinico, Modena, Italy., Salsi V; Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy., Tupler R; Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.; Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.; Li Weibo Institute for Rare Diseases Research at the University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2023 Feb; Vol. 103 (2), pp. 242-246. Date of Electronic Publication: 2022 Oct 23.
DOI: 10.1111/cge.14250
Abstrakt: Facioscapulohumeral muscular dystrophy (FSHD) has been associated with the deletion of an integral number of 3.3 kb units of the polymorphic D4Z4 repeat array at 4q35. The prenatal identification of this defect can be carried out on chorionic villi or amniocytes, whereas preimplantation genetic testing for monogenic disorders (PGT-M) requires molecular markers linked to the D4Z4 allele of reduced size. In this context the reliability of this association is crucial. To test the informativeness of the nearby polymorphic markers we investigated recombination at 4q35 using the polymorphic markers D4S1523, D4S163 and D4S139 positioned at 0.55, 0.5 and 0.21 Mb proximal to the D4Z4 array respectively. We determined the probability of recombination events to occur in the D4Z4-D4S1523 interval considering 86 subjects belonging to 12 FSHD families and found a recombination frequency of 14% between D4Z4 and D4S1523. Our study also revealed the occurrence of de novo variants and germline mosaicism. These findings highlight the recombinogenic nature of the 4q subtelomere and indicate that caution should be taken when interpreting PGT-M results. It is advisable that a woman who underwent a PGT-M cycle undertakes a prenatal DNA analysis to confirm the size of the D4Z4 alleles carried by the fetus.
(© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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