Clinical and molecular characterization of lipoid proteinosis in three Indian families

Abstract

Background: Lipoid proteinosis (LP) is a rare autosomal recessive disorder characterized by deposition of hyaline material in the skin, mucous membrane, and multiple organs resulting in varied manifestations such as scarring and thickening of the skin, beaded papules, and hoarseness of voice. It results from mutations in the gene encoding extracellular matrix protein 1 (ECM1). The objectives of this study are to find the mutation spectrum of the ECM1 gene in the Indian children and study the genotype-phenotype correlation. Materials and Methods: This pilot study included three unrelated Indian families with the clinical diagnosis of LP. Next-generation sequencing was done to look for ECM1 gene mutations in the proband and was confirmed by Sanger sequencing in their siblings and parents. Chromosomal microarray was done wherever necessary. Results: All six children from three unrelated consanguineous families had characteristic clinical features of LP. Two children in family 1 exhibited systemic features like temporal lobe epilepsy in one and central precocious puberty in the other. One child from family 1 and one child from family 3 had short stature. Genetic analysis revealed novel homozygous missense variation in exon 7 (c.856T>C) in family 1 and homozygous nonsense variation in exon 8 (c.1327C>T) in family 2 of the ECM1 gene. Family 3 revealed a large homozygous deletion of the ECM1 gene which has not been previously described. Conclusion: All the three families had clinical heterogeneity. This study documented two novel mutations in the ECM1 gene. Skin severity and systemic involvement were associated with missense mutation. Confirmation of ECM1 gene mutation is necessary for proper genetic counseling.

Keywords

• autosomal recessive
• ecm1 gene
• lipoid proteinosis
• novel mutation