European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Normal variation, population genetics, genetic epidemiology
P1177. Retrospective study of Clinical and histological
manifestations of IP in Adults
S. Hadj-Rabia 1 , A. Rimella 1 , S. Fraitag 2 , Y. de Prost 1 , A. Smahi 3 , C. Bodemer 4 ;
1 Dermatology, Necker-Enfants malades Hospital, France, 2 Dermatopathology,
Necker-Enfants malades Hospital, France, 3 INSERM-U781, Necker-Enfants
malades Hospital, France, 4 Dermatology, Centre Maladies Genetiques à Expression
Cutanée, Necker-Enfants malades Hospital, France.
Introduction. Incontinentia pigmenti (IP) is a rare X dominant genodermatosis
related to mutations of NEMO gene. It affects mostly female
patients and is usually lethal for males in utero. The skin lesions may
occur in 4 classically successive diagnostic stages: erythema and vesicles,
(stage 1); verrucous (stage 2); linear hyperpigmentation (stage
3); and pallor and scarring (stage 4).In adults, manifestations are skin
involvement (stage 4) and teeth and nail anomalies.
Patients and Methods
25 adults patients with molecular diagnosis of IP, were enrolled for
clinical examination. Skin, ocular, neurological and stomatological manifestations
were recorded using a standard form. Skin biopsy was
performed.
Results. 25 patients fulfilled the criteria : the diagnosis was made in
adulthood in 52%of the patients. Stage 4 was constant (100%) stage
3 and 2 were found in 11 and 1 patients respectively. Other manifestations
were: woolly hair (44%), nails (84%), teeth (92%), ocular (48%),
mammary (28%) and neurological (12%) anomalies. Histology shows
apoptotic kératinocytes, absence of follicles and sweat glands (stages
3 and 4), hypopigmentation and atrophic epidermis (stage 4).
Discussion. Diagnosis of IP was delayed in 52% of the patient and
based on the constant association of stage 4 lesions and teeth anomalies.
Interestingly, apoptosis persists in adulthood and was associated
to absence of both sweat glands and follicles. Dermatological examination
of patients with several miscarriages may be helpful to detect IP
as a rare cause of spontaneous abortion. Moreover, histology confirms
clinical suspicion of the disease and should be include in IP criteria.
P1178. The role of Toll-like Receptor 4 polymorphisms and
CARD15/NOD2 mutations in the susceptibility and phenotype
in Inflammatory Bowel Disease: reports of a survey in Southern
Italy population.
L. Rigoli 1 , C. Romano 1 , C. Di Bella 1 , V. Procopio 1 , M. Amorini 1 , G. Lo Giudice 1 ,
D. Magnoli 1 , C. Salpietro 1 , W. Fries 2 ;
1 Department of Pediatrics, Medical School, University of Messina, Messina,
Italy, 2 Department of Medicine, Medical School, University of Messina, Messina,
Italy.
Single nucleotide polymorphisms in the Toll-like Receptor 4 (TLR4)
and CARD15/NOD2 genes have recently been shown to be associated
with Inflammatory Bowel Disease (IBD), but whether this susceptibility
extends to all ethnic groups remains unknown. The aim of our
study was to evaluate the CARD15/NOD2 and TLR4 gene mutations
in a Southern Italy population.
Thirty two ulcerative colitis (UC) patients (mean age, 47 yrs), 79 Crohn’s
disease (CD) patients (mean age, 46 yrs) and 103 healthy ethnically
matched controls were genotyped for three CARD15/NOD2 variants
(R702W, G908R, and L1007finsC) and for TLR4 gene polymorphisms
(D299G and T399I). The allele frequency of the different genotypes
was compared and genotype-phenotype correlation was performed.
Comparison of the frequency between patients and controls and the
association to the phenotype was performed by chi-square test or
Fisher’s exact test where appropriate.
No significant association of the two TLR4 gene mutations with UC or
CD was observed (allele frequency: D299G- controls 3.5%, UC 3.6%,
CD 3.3%; T399I- controls 2.9%, UC 2.8%, CD 2.9%). The frequency of
the frameshift mutation L1007finsC of the CARD15/NOD2 gene was
significantly higher in CD patients (9.3%; p=0.0001) compared with
controls (2.9%) or patients with UC (2.7%). In CD patients the frequency
of R702W mutation was significantly higher (8.3%; p