Alternative titles; symbols
HGNC Approved Gene Symbol: NIPAL4
Cytogenetic location: 5q33.3 Genomic coordinates (GRCh38) : 5:157,460,213-157,474,722 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 5q33.3 | Ichthyosis, congenital, autosomal recessive 6 | 612281 | Autosomal recessive | 3 |
By in silico analyses, Lefevre et al. (2004) cloned NIPAL4, which they called ichthyin. The deduced 404-amino acid protein has a calculated molecular mass of 44 kD. The protein has several putative transmembrane domains and shares approximately 75% sequence identity with the mouse and rat orthologs. It is predicted to localize in the plasma membrane, but does not possess a signal sequence. RT-PCR detected expression of ichthyin at high levels in brain, lung, stomach, skin, and leukocytes, and in all other tissues tested except liver, thyroid, and fetal brain, in which no expression was detectable. Strong expression was observed in cultured keratinocytes from normal skin biopsies; expression was weaker in cultured fibroblasts from the same skin biopsies, in placenta and in lymphocytes.
Lefevre et al. (2004) determined that the NIPAL4 gene contains 6 exons.
By in silico and sequence analyses, Lefevre et al. (2004) mapped the NIPAL4 gene to chromosome 5q33.
In 23 patients from 14 consanguineous families with nonsyndromic autosomal recessive congenital ichthyosis (ARCI6; 612281), Lefevre et al. (2004) identified 6 homozygous mutations in the NIPAL4 gene (see, e.g., 609383.0001-609383.0002).
Dahlqvist et al. (2007) studied 27 patients from 18 ARCI families with the specific ultrastructural features of the epidermis that characterize electron microscopy-analyzed ichthyosis designated type III (EM type III). Mutation screening of NIPAL4 revealed 4 different missense or splice site mutations (see, e.g., 609383.0003-609383.0004) in affected members from 16 of 18 (89%) families with these characteristics of ARCI EM type III.
In affected members of 3 consanguineous Algerian families with autosomal recessive congenital ichthyosis-6 (ARCI6; 612281), Lefevre et al. (2004) identified a homozygous 247C-T transition in exon 2 of the NIPAL4 gene, resulting in an arg83-to-ter (R83X) substitution.
In affected members of 7 consanguineous families with autosomal recessive congenital ichthyosis-6 (612281), Lefevre et al. (2004) identified a homozygous 341C-A transversion in exon 4 of the NIPAL4 gene, resulting in an ala114-to-asn (A114N) substitution. One of the families was from Colombia, 3 were from Turkey, and 3 were from Algeria.
In a study of 27 patients from 18 families with autosomal recessive congenital ichthyosis-6 (612281) characterized by electron microscopy (EM) as type III (ARCI EM type III), with abnormal lamellar bodies in stratum granulosum and perinuclear, elongated membranes, Dahlqvist et al. (2007) found a 527C-to-A transversion in exon 4 of the NIPAL4 cDNA that led to an ala176-to-asp (A176D) amino acid substitution. The mutation was found in 37 of the 54 alleles examined.
In a patient with autosomal recessive congenital ichthyosis-6 (612281), Dahlqvist et al. (2007) identified compound heterozygosity for a G-to-A transition at the splice donor site of exon 5 of the NIPAL4 gene, and an A176D mutation (609383.0003). DNA sequencing showed that the mutant mRNA retained 68 nucleotides of intronic sequence by the activation of a cryptic splice site, which resulted in a premature stop codon.
Dahlqvist, J., Klar, J., Hausser, I., Anton-Lamprecht, I., Pigg, M. H., Gedde-Dahl, T., Jr., Ganemo, A., Vahlquist, A., Dahl, N. Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis. J. Med. Genet. 44: 615-620, 2007. [PubMed: 17557927] [Full Text: https://doi.org/10.1136/jmg.2007.050542]
Lefevre, C., Bouadjar, B., Karaduman, A., Jobard, F., Saker, S., Ozguc, M., Lathrop, M., Prud'homme, J.-F., Fischer, J. Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis. Hum. Molec. Genet. 13: 2473-2482, 2004. [PubMed: 15317751] [Full Text: https://doi.org/10.1093/hmg/ddh263]