Centre for Arab Genomic Studies

A Division of Sheikh Hamdan Award for Medical Sciences

The Catalogue for Transmission Genetics in Arabs

CTGA Database

Nonbullous Congenital Ichthyosiform Erythroderma 1

Alternative Names
NCIE1
IECN1
Ichthyosiform
Erythroderma,
BROCQ
Congenital, Nonbullous Form
Nonbullous
Congenital
Ichthyosiform
Erythroderma 1
NCIE
CIE
WHO International Classification of Diseases
Congenital malformations, deformations and
chromosomal abnormalities
OMIM Number
242100
Mode of Inheritance
Autosomal recessive
Gene Map Locus
17p13.1, 17pter-p13.1, 14q11.2
Description
Ichthyosis is a clinically and genetically
heterogeneous group
of
disorders of
keratinization characterized by a significant and
incapacitating scaling of the skin. Most forms
are congenital and display different modes of
inheritance. Two major forms have been
described clinically: (1) the primary forms, in
which the disorder is largely limited to the skin,
and (2) the ichthyosiform syndromes, in which
ichthyosis is a part of a multisystem disorder. In
the first group, two major forms have been
defined, lamellar ichthyosis (LI) and nonbullous
congenital ichthyosiform erythroderma (NCIE).
Nonbullous
congenital
ichthyosiform
erythroderma is an inflammatory form of
ichthyosis with an estimated frequency of
1/300,000 and is characterized by prominent
erythroderma and fine white, superficial,
semiadherent scales. At birth, 90 % of the
affected individuals present as collodion babies.

Palmoplantar keratoderma, often with painful

fissures, digital contractures, and loss of pulp
volume are also present in affected patients. In
50 % of the cases, a nail dystrophy including
ridging, subungeal hyperkeratosis, or hypoplasia
has been described. Ectropion, eclabion, scalp
involvement, and loss of eyebrows and lashes
are also seen. Histologic features include
hyperkeratosis, an increase in stratum corneum
thickness, a normal or prominent granular layer,
and
increased
mitoses
point
to
a
hyperproliferative epidermal defect.
Molecular Genetics
Mutations in any of the three known causative
genes, TGM1, ALOXE3 or ALOX12B, can
lead either to NCIE or LI. Transglutaminases,
including the product of the TGM1 gene,
catalyze
formation
of
epsilon-(gammaglutamyl)-lysine crosslinks in proteins and
thereby stabilize biological structures. In
epidermis, TGM1 is required for the formation
of the cross-linked envelope. Point mutations in
the TGM1 gene cause deficits in enzyme
activity.

Epidemiology in the Arab World

Egypt
Shawky et al. (2004) investigated forty-three
autosomal recessive congenital ichthyosis
(ARCI) Egyptian individuals in 16 families with
severe lamellar ichthyosis (LI) and 10 families
with congenital ichthyosiformis erythroderma
(CIE). Shawky et al. (2004) identified 5 alleles
in two Egyptian families as having intron5/exon-6 splice acceptor mutation recognized
by the MspI restriction endonuclease. This
promoted to a frequency of 9.6% for this
mutation (5 splice-mutation alleles/52 alleles
tested). Shawky et al. (2004) extended their
dataset to update the detection of R142H
mutation in 4 CIE Egyptian families and one LI
phenotype (frequency of 28.8%; 15/52).

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However, they did not observe the R141H

among the Egyptian population. There was also
no correlation between phenotype and genotype
in the study. The mutant alleles detected in
intron-5 acceptor splice-site were associated
with the other extreme of CIE phenotypes rather
than the severe LI form.

References
Shawky RM, Sayed NS, Elhawary NA.
Mutations in transglutaminase 1 gene in
autosomal recessive congenital ichthyosis in
Egyptian families. Dis Markers. 2004;
20(6):325-32.
Contributors
Ghazi O. Tadmouri: 6.9.2005

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