Preimplantation genetic diagnosis of X-linked Charcot-Marie-Tooth disease by indirect linkage analysis

Abstract

Objective: To present methodical approach of preimplantation genetic diagnosis (PGD) as an option for an unaffected pregnancy in reproductive-age couples who have a genetic risk of the X-linked dominant peripheral neuropathy Charcot-Marie-Tooth type 1 disease.

Patients and methods: We performed PGD of X-linked Charcot-Marie-Tooth type 1 disease using haplotyping/indirect linkage analysis, when during analysis we reach to exclude embryos that carry a high-risk haplotype linked to the causal mutation p.Leu9Phe in the GJB1 gene.

Results: Within the PGD cycle, we examined 4 blastomeres biopsied from cleavage-stage embryos and recommended 3 embryos for transfer. Two embryos were implanted into the uterus; however, it resulted in a singleton pregnancy with a male descendant. Three years later, the couple returned again with spontaneous gravidity. A chorionic biopsy examination of this gravidity ascertained the female sex and a pericentric inversion of chromosome 5 in 70% of the cultivated foetal cells.

Conclusion: Using indirect linkage analysis, PGD may help to identify genetic X-linked defects within embryos during screening, thereby circumventing the potential problems with abortion.

Keywords: Análisis de ligamiento indirecto; Enfermedad de Charcot-Marie-Tooth ligada al cromosoma X; Haplotipificación; Haplotyping; Inactivación del cromosoma X; Indirect linkage analysis; X-chromosome inactivation; X-linked Charcot-Marie-Tooth disease.