Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010;220(1):8-14.
doi: 10.1159/000265757. Epub 2009 Dec 10.

NIPAL4/ichthyin is expressed in the granular layer of human epidermis and mutated in two Pakistani families with autosomal recessive ichthyosis

Muhammad Wajid  1 , Mazen Kurban, Yutaka Shimomura, Angela M Christiano
Affiliations

NIPAL4/ichthyin is expressed in the granular layer of human epidermis and mutated in two Pakistani families with autosomal recessive ichthyosis

Muhammad Wajid et al. Dermatology. 2010.

Abstract

Background: Autosomal recessive congenital ichthyosis (ARCI) can be divided into 3 types including lamellar ichthyosis (OMIM 242304), nonbullous congenital ichthyosiform erythroderma (OMIM 242100) and harlequin ichthyosis (OMIM 242500). The last type is uncommon since newborns with harlequin ichthyosis usually die shortly after birth. Several genes have been linked to ARCI, but these represent only 60% of the known genetic causes of this condition.

Methods: After having performed a linkage analysis, we analyzed the DNA of 2 consanguineous Pakistani families with ARCI for NIPAL4 mutations and performed in situ hybridization (ISH) for NIPAL4 mRNA in the epidermis.

Results: The haplotype analysis revealed a linkage to chromosome 5, and we identified a recurrent missense mutation, p.A176D, in affected individuals from both families. We also determined by ISH that NIPAL4 mRNA is highly expressed in the granular cell layer of the epidermis, consistent with the ARCI phenotype.

Conclusion: Our results expand the spectrum of the clinical manifestations of the NIPAL4 gene and further extend our understanding of its molecular function.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Autosomal recessive inheritance is clearly seen in both pedigrees.
Fig. 2
Fig. 2
a Severe itching in an affected individual. b Patient presenting with atopic dermatitis. c Fine whitish scales over the face of an affected individual. d Facial hyperkeratosis with ectropion, resembling LI. e Semiadherent yellowish-to-whitish scales overlying an erythematous base. f Joint contractures of the fingers with nail clubbing. g Palmar hyperkeratosis. h Fine whitish scales overlying an erythematous base, involving the neck and chest. Typical findings in NBCIE. i Brown reticulated ichthyosis involving the chest and neck.
Fig. 3
Fig. 3
Homozygous mutation characterized by C → A transition leading to the substitution of aspartic acid (D) for alanine at codon 176 (A).
Fig. 4
Fig. 4
a ISH reveals the expression of NIPAL4 mRNA in the granular cell layer of the epidermis (arrow). b Negative control.
See this image and copyright information in PMC

References

    1. Farasat S, Wei MH, Herman M, Liewehr DJ, Steinberg SM, Bale SJ, et al. Novel transglutaminase-1 mutations and genotype-phenotype investigations of 104 patients with autosomal recessive congenital ichthyosis in the USA. J Med Genet. 2009;46:103–111. - PMC - PubMed
    1. Lefèvre C, Bouadjar B, Karaduman A, Jobard F, Saker S, Özguc M, et al. Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis. Hum Mol Genet. 2004;13:2473–2482. - PubMed
    1. Griffiths WAD, Judge MR, Leigh IM. Disorders of keratinization. In: Champion RH, Burton JL, Burns DA, Breathnach SM, editors. Textbook of Dematology. ed 6. Oxford: Blackwell Science; 1998. pp. 1483–1530.
    1. Eckl KM, de Juanes S, Kurtenbach J, Nätebus M, Lugassy J, Oji V, et al. Molecular analysis of 250 patients with autosomal recessive congenital ichthyosis: evidence for mutation hotspots in ALOXE3 and allelic heterogeneity in ALOX12B. J Invest Dermatol. 2009;129:1421–1428. - PubMed
    1. Lugassy J, Hennies HC, Indelman M, Khamaysi Z, Bergman R, Sprecher E. Rapid detection of homozygous mutations in congenital recessive ichthyosis. Arch Dermatol Res. 2008;300:81–85. - PubMed

Publication types