Acta Dermato-Venereologica 99-9CompleteContent | Page 22

828 SHORT COMMUNICATION Next Generation Sequencing Uncovers a Rare Case of X-linked Ichthyosis in an Adopted Girl Homozygous for a Novel Nonsense Mutation in the STS Gene Andrea DIOCIAIUTI 1# , Adriano ANGIONI 2# , Elisa PISANESCHI 2 , Maria MARGOLLICCI 3 , Renata BOLDRINI 3 , Viola ALESI 2 , Antonio NOVELLI 2 , Giovanna ZAMBRUNO 1 and May EL HACHEM 1 Dermatology Unit, 2 Molecular Genetics Laboratory and 4 Pathology Unit, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio, 4, IT-00165 Rome, and 3 Molecular Medicine and Genetics AOU, Siena, Italy. E-mail: [email protected] # These authors contributed equally. 1 Accepted Mar 4, 2019; E-published Mar 5, 2019 X-linked ichthyosis (XLI, OMIM #308100) is the second most common form of inherited ichthyosis after ich­ thyosis vulgaris. It almost exclusively affects males and the estimated prevalence ranges from 1 in 1,500 to 1 in 6,000 males (1–3). XLI is caused by mutations in the STS gene on chromosome Xp22.31 encoding for the steroid sulfatase (STS) enzyme (1, 4). Most patients (85–90%) carry a genomic deletion comprising the entire STS gene, while point mutations or partial deletions account for about 10% of cases. XLI manifests more frequently in the neonatal period with generalized whitish, lamellar desquamation, which over time is replaced by the typical polygonal, dark scales that are more prominent on legs and arms (1, 4). We report an exceptional case of XLI in an adopted Indian girl homozygous for a previously undescribed nonsense mutation in the STS gene. CASE REPORT The patient is an 8-year-old female child of Indian origin who was referred to our rare skin disease center for suspicion of ichthyosis. She had been adopted 1 year before, and personal and family his­ tories were unavailable. Physical examination showed diffuse dark scales which were larger on the legs and foot dorsa, smaller on the arms and thighs, and arranged in a reticular pattern on the thorax and abdomen (Fig. 1). The scalp showed fine, light desquamation, while the flexural creases presented minimal hyperkeratosis (Fig. 1b). The palmoplantar surfaces were unaffected. In addition, the child had mild signs of atopic dermatitis with lichenification on the right antecubital fossa, neck (Fig. 1d), perioral area and eyelids. She was in ophthalmological follow-up for reduced visual acuity due to retinopathy of prematurity. Neuropsychiatric evaluation did not reveal behavioural abnormalities. Her weight was below the 3 rd percentile and her height between the 3 rd and the 10 th per­ centile. Laboratory examinations showed elevated total IgE (248 IU/ml) and vitamin D deficit (9.3 ng/dl), for which vitamin D supplementation was started. Following informed consent, a skin biopsy was obtained, together with blood sampling for genetic analysis. Histopatho­ logical examination showed compact hyperkeratosis, a normal granular layer, and follicular plugging. Immunohistochemistry revealed filaggrin expression similar to control skin. Ultrastructural examination did not show any lipid droplets, cholesterol clefts or membranous structures in the epidermal granular and horny layers, where numerous melanosome remnants were observed. Keratohyaline granules were normal in size and distribution. Variant analysis was performed using a customized next genera­ tion sequencing (NGS) panel containing all known inherited ich­ thyosis genes (5) except FLG. A homozygous nonsense mutation c.1116G>A (p.Trp372*) in exon 8 of the STS gene (NM_000351.4, NP_000342.2) (Fig. S1a 1 ) was identified. Sanger sequencing confirmed the presence of the homozygous G>A transversion (Fig. S1b 1 ). Mutation p.Trp372* has not been previously reported, and is not recorded in any database of human genetic variations (1,000 Genomes, Exome Variant Server and Exome Aggregation Consortium database – ExAC). Moreover, the dosage of STS https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3162 1 Fig. 1 Clinical features of an 8-year-old Indian girl affected with X-linked ichthyosis. Large, polygonal, brownish scales on the calves (a); fine grayish scales on the back of thighs and minimal hyperkeratosis of the popliteal folds (b); hyperkeratosis and small to medium size scales on the foot dorsa and ankles (c); adherent, small scales arranged in a reticular pattern on the abdomen, lichenification on the antecubital right fossa and on the neck (d). doi: 10.2340/00015555-3162 Acta Derm Venereol 2019; 99: 828–830 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.