observing the response to treatment through time. It is some-
times necessary to perform another biopsy or have the slides
re-examined to get the correct diagnosis, as many other verru-
cous pathologies other than viral warts can affect the nail unit.
Finally, the clinician has to remember that VEN may be associ-
ated with systemic abnormalities.
N.G. Di Chiacchio,
* E. Haneke,
N. Di Chiacchio,
Dermatology Department, University Hospital “Dr. Jos
alez”, Universidad Aut
onoma de Nuevo Le
on, Monterrey, M
Dermatology Department, Hospital do Servidor P
ublico Municipal de S
ao Paulo, Brazil,
Dermatology Department, Faculty of Medicine
of ABC, S
ao Paulo, Brazil,
Department of Dermatology, Inselspital,
University of Bern, Bern, Switzerland,
Dermatology Clinic Dermaticum,
Freiburg im Breisgau, Germany,
Centro de Dermatolog
Instituto CUF, Porto, Portugal,
Department of Dermatology, Academic
Hospital, University of Gent, Gent, Belgium
*Correspondence: N.G. Di Chiacchio. E-mail: email@example.com
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Novel PNPLA1 mutations in two
Italian siblings with autosomal
recessive congenital ichthyosis
Autosomal recessive congenital ichthyoses (ARCI) are a clini-
cally and genetically heterogeneous group of non-syndromic
ichthyoses due to mutations in at least 9 genes, including
PNPLA1 (Patatin-Like Phospholipase Domain-Con-
taining Protein 1) is strongly expressed in the epidermal granular
and has been recently shown to play a crucial role in
epidermal x-O-acylceramide biosynthesis and skin barrier integ-
rity both in mice and humans.
Concomitantly, several ARCI
families carrying PNPLA1 mutations have been described con-
ﬁrming that most mutations occur in the highly conserved pata-
tin core domain.
We report the identiﬁcation of two novel
missense mutations in PNPLA1 in two Italian sisters affected
with ARCI characterized by a cyclic disease course.
A 3-year-old female child was addressed to our centre for
diagnostic ascertainment of her congenital ichthyosis. At birth,
she presented generalized erythema which almost completely
cleared by the third month. From the ﬁfth month, the disease
recurred manifesting a cyclic course with a periodicity of about
6 weeks. Erythema and hyperkeratosis were followed by scaling,
ending with almost normal skin. Physical examination showed a
diffuse slight hyperkeratosis with small ﬁne scales and scattered
erythematous patches on the chest, abdomen and face (
Scaling was more evident at the edge of erythematous areas of
the abdomen (Fig. 1a), on feet and ankles, and on the scalp
showing thicker conﬂuent scales (Fig. 1b). Nails and palmoplan-
tar surfaces were not affected, while folds were involved
(Fig. 1c). The patient also presented hypohidrosis and reduced
heat tolerance. The younger sister presented a similar ichthyotic
Figure 1 Clinical features. Erythematous and slightly hyperkera-
totic patches more evident on the lower abdomen and left axillary
fold (a); hyperkeratosis and scaling on the scalp and eyebrows,
whitish to light brown scales on the forehead and minimal ery-
thema of the face (b); Hyperkeratosis on the right axillary fold (c).
The younger sister presents erythema on the cheeks and mild
hyperkeratosis with small ﬁne whitish scales on the face at the age
of 2 years (d).
© 2017 European Academy of Dermatology and Venereology
2018, 32, e86–e121
Letters to the Editor