SPINK5 and Netherton syndrome: novel deleterious mutation

Background and Aim : Netherton syndrome (NS) is a sever skin disorder characterized by congenital ichthyosiform dermatosis, a specific hair-shaft abnormality, and high IgE levels. Some affected babies which are born with collodion membrane subsequently, prone to dehydration and sepsis. Affected infants may also fail to grow and gain weight and older children remain underweight and of short stature. The frequency of this disease is estimated 1 in 200,000 newborns. Methods : The patient was 9 months infant died due to NS. The affected infant had been suffered congenital erythroderma, food allergies, eczema, hay fever, and frequent infections. Whole exome sequencing (WES) has been done to identify the genetic basis of the disorder. After identifying the mutation, co-segregation analysis applied through the patient s relatives. Results : In this study we found novel homozygous mutation (c.236dupG) in exon 4 of the serine protease inhibitor Kazal-type 5 (SPINK5) gene. This variation result in frameshift R79fs* mutation, which leads to truncated protein. Our bioinformatic analysis showed that the mutation is deleterious and hereditary because the patient s parents and her relatives were heterozygous. Conclusion : In agreement with previous studies our finding once again state that the SPINK5 gene s pathogenic mutations can be life-threatening because of its important role in skin barrier function and desquamation. For understanding the specific links of each pathogenic mutations with clinical manifestations in NS patients in-vitro analysis are essential to be done.

کلیدواژه ها:

Netherton syndrome ، SPINK5 ، WES ، Dermatosis