Novel mutation in PNPLA1 gene, the causative defect in Lamellar Icthyosis (LI)

Introduction: Lamellar ichthyosis(LI) is an autosomal recessive and heterogeneous group of congenital disorders. Mutations in one of the TGM1, ALOXE3, ALOX12B, ABCA1, NIPAL4, CYP4F22, PNPLA1, LIPN, CERS3 genes can cause LI. Infants with LI disorder are generally born with waxy skin that is typically shed within the first two weeks of life and then affected babies have scaly skin. Other signs and symptoms of the condition include lips that turn outwards, infections, dehydration, respiratory problems, frequent skin itching and dark stain on the skin. Methods: We analyzed a five-year-old girl with LI that was born of a consanguineous marriage in Hormozgan province of Iran with no history of LI in her family. Blood sample was prepared for targeted NGS (Next Generation Sequencing). To validate the mutations, sanger sequencing was performed in family members and the data were analyzed. Results:A novel missense homozygote mutation (c.939-952 Del 13 Nt ins T) was identified in PNPLA1 gene. Sanger sequencing showed that her parents carry one copy of the mutated gene, but typically do not have any symptoms of the LI .Conclusions: This is the first case in the literature describing a novel c.939-952 Del 13 Nt Ins T mutation in PNPLA1 gene. NGS and complimentary investigations were done for the patient and sequencing results showed that she is homozygous for the noted mutation in PNPLA1 gene. Regarding the identification of the parents’ heterozygosity, it is possible to prevent the occurrence of this rare disease in Hormozgan province during the next pregnancy.

Keywords:

Lamellar Ichthyosis , PNPLA1 , NGS