Successful pre-implantation genetic testing for autosomal recessive cutis laxa: clinical utility of a...

Pre-implantation genetic testing for monogenic disorders (PGT-M) enables couples at risk of transmitting serious genetic disorders to their offspring to give birth to healthy children. Here, we present an illustrative case of the use of PGT-M in a couple who were both carriers of autosomal recessive cutis laxa (ARCL) and describe the application of PGT-M in our reproductive center using a multidisciplinary team approach.

The couple experienced four adverse pregnancy outcomes, and both partners were subsequently identified as carriers of ARCL caused by PYCR1 gene variants during a genetic evaluation. They chose PGT-M after counseling and being fully informed of the potential risks and benefits. Trophectoderm cells were biopsied on day 5 or 6 and whole-genome amplification was performed using multiple annealing and looping-based amplification cycles (MALBAC). Mutated allele revealed by sequencing with aneuploidy and linkage analysis (MARSALA) was used to detect the copy number variations and the carrier status of the PYCR1 gene. Prenatal diagnosis was performed to validate the PGT-M results. Psychological support was provided throughout.

PGT-M was successfully performed, and transfer of a euploid blastocyst carrying a paternal variant in the third cycle resulted in a pregnancy. Prenatal diagnosis confirmed the PGT-M results. The woman gave birth to a healthy boy with normal skin and growth and developmental milestones.

This study illustrates the clinical applicability of PGT-M in ARCL carrier couples, highlighting the importance of multidisciplinary consultation, and the implementation of comprehensive genetic counseling protocols and tailored psychosocial interventions.