Manifestation of diffuse yellowish keratoderma on the palms and soles in autosomal recessive congenital ichthyosis patients may be indicative of mutations in NIPAL4.

[lamellar ichthyosis]

Ichthyosis is a heterogeneous disorder characterized by abnormal skin scaling over the whole body . Autosomal recessive congenital ichthyosis (ARCI ) comprises various forms , the most important of which are lamellar ichthyosis (LI ) and congenital ichthyosiform erythroderma (CIE ). Seven genes have been identified to be causative of ARCI , and these account for disease in 60 -80 % of the patients . There is notable phenotypic overlap between the major forms of ARCI , and a strong genotype-phenotype correlation has not been found . Here , we initially aimed to identify the causative gene in a large Iranian ARCI pedigree , and subsequently performed genetic analysis on four other affected pedigrees . A genotype-phenotype correlation was sought . Whole genome homozygosity mapping using high -density single nucleotide polymorphism chips was performed on the large pedigree . Linkage to chromosome 5 and a mutation in NIPAL 4 causing p .G 297 R were identified . The same mutation was also identified in two of the remaining four Iranian pedigrees . Two of the NIPAL 4 mutation bearing pedigrees were classified as CIE and one as LI . Notably , all NIPAL 4 mutation -bearing patients manifested diffuse yellowish keratoderma on the palms and soles . We provide evidence suggesting presentation of this diffuse yellowish keratoderma may be indicative of mutations in NIPAL 4 , providing an easily assessable genotype-phenotype correlation .