Abstract
OBJECTIVE: To investigate a Chinese family with epidermolysis bullosa palmoplantar keratosis, analyze the mutation loci in this family lineage, and perform preimplantation genetic testing using assisted reproductive technology to enable affected members of this Chinese family to have unaffected offspring. METHODS: Clinical information and blood samples were collected from all affected family members to extract genomic DNA. We detected a mutation site in the KRT9 gene through whole-exome sequencing, then verified this family line's Keratin-9 gene variant locus using Sanger sequencing. After the pathogenicity was clarified, blastocyst trophoblast cells were extracted for Preimplantation Genetic Testing for Monogenic (PGT-M)(Single Gene) Disorders using the in vitro fertilization embryo transfer technique, and suitable embryos were selected for transfer. Amniocentesis was performed to extract fetal exfoliated cells for prenatal diagnosis at 18 weeks of fetal development. RESULTS: A heterozygous mutation c.503T > C (p. Leu168Ser), which results in the substitution of a leucine for a serine (p. Leu168Ser), was detected in the KRT9 gene in the proband and his father, which is located in the highly conserved helix 1 A region of Keratin 9, resulting in an abnormal function of the intermediate filamentous proteins expressed by Keratin 9 encodes genes which are expressed in the palmo-plantar regions of the epidermis, and the patients of the family present with pronounced palmar-plantar keratoderma. CONCLUSION: We identified the c.503T > C (p. Leu168Ser) missense mutation in exon 1 of the KRT9 gene as the cause of KRT9-palmoplantar epidermal differentiation disorder (KRT9-pEDD) in a Chinese family. Under the guidance of comprehensive genetic counseling, employing PGT-M, we successfully prevented the transmission of the KRT9-pEDD pathogenic variant, resulting in the birth of a healthy child.