Background: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of skin disorders. Several mutant genes are identified in ARCI but the association between genotype and phenotype is poorly understood.
Materials and methods: In search for genotype-phenotype correlations in ARCI we selected 27 patients from 18 families with specific ultrastructural features of the epidermis. The electron microscopy (EM) picture was characterised by abnormal lamellar bodies and elongated membranes in stratum granulosum classified as ARCI EM-type III. DNA samples from a subset of affected individuals were screened for homozygous genomic regions and a candidate gene region was identified on chromosome 5q33. The region coincides with the ichthyin gene, previously reported as mutant in ARCI.
Results: Mutation screening of ichthyin revealed missense or splice site mutations in affected members from 16 out of 18 families (89%) with characteristics of ARCI EM-type III. In a control group of 18 ARCI patients without EM findings consistent with type III, we identified one individual homozygous for a missense mutation in ichthyin.
Discussion: Our findings indicate a strong association between ultrastructural abnormalities in the granular layer of epidermis and ichthyin mutations. The results also suggest that EM provides a tool for specific diagnosis in a genetically homogenous subgroup of ARCI patients.
- Autosomal recessive ichthyosis
- SNP array
- electron microscopy
- ichthyin gene mutations