Acta Dermato-Venereologica 99-12CompleteContent | Page 15

1110 CLINICAL REPORT Electron Microscopic and Immunohistochemical Findings of the Epidermal Basement Membrane in Two Families with Nail-patella Syndrome Satoru SHINKUMA 1,2 *, Hideki NAKAMURA 2 , Manami MAEHARA 1 , Shota TAKASHIMA 2 , Toshifumi NOMURA 2 , Yasuyuki FUJITA 2 , Satoshi HASEGAWA 3 , Kazuko C. SATO-MATSUMURA 4 , Riichiro ABE 1 and Hiroshi SHIMIZU 2 Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 2 Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, 3 Higashikariki Dermatology Clinic, and 4 Department of Dermatology, JCHO Sapporo Hokushin Hospital, Sapporo, Japan 1 Nail-patella syndrome is an autosomal dominant dis­ order characterized by nail dysplasia and skeletal anomaly. Some patients have been shown to have ultrastructural abnormalities of the glomerular base- ment membrane that result in nephrosis. However, little has been reported on the epidermal basement membrane in this condition. This paper reports 2 fa- milies with nail-patella syndrome. Direct sequencing analysis of LMX1B revealed that family 1 and family 2 were heterozygous for the mutations c.140-1G>C and c.326+1G>C, respectively. To evaluate the epidermal basement membrane zone, ultrastructural and immu- nohistochemical analyses were performed using skin specimens obtained from the dorsal thumb. Electron microscopy showed intact hemidesmosomes, lamina lucida, lamina densa, and anchoring fibrils. Immuno­ fluorescence studies with antibodies against com- ponents of the epidermal basement membrane zone revealed a normal expression pattern among the com- ponents, including type IV collagen. These data sug- gest that nail dysplasia in patients with nail-patella syndrome is not caused by structural abnormalities of the epidermal basement membrane. Key words: epidermal basement membrane; glomerular ba- sement membrane; hereditary osteo-onychodysplasia; LIM- homeodomain protein; LIM-homeobox transcription factor 1ß; LMX1B; type IV collagen. Accepted Sep 12, 2019; E-published Sep 12, 2019 SIGNIFICANCE Nail-patella syndrome is caused by mutations in the LMX1B gene that lead to anomalies of dorsal-ventral limb patter- ning. Some patients show abnormalities of the glomeru- lar basement membranes; however, little is known about the epidermal basement membrane. This study found no abnormalities in the epidermal basement membrane zone. This finding suggests that nail deformities can be caused by the abnormal development of dorsal limb structures rather than dysfunction of the epidermal basement membrane. eye, and dopaminergic and serotonergic neurones (3–7). Patients with NPS sometimes have nephrosis-associated renal disease (1). LMX1B regulates the expressions of type IV collagen (COL4) α3 and α4 (α3(IV) and α4(IV)) chains required for normal morphogenesis of GBM (4). Kidneys of some patients with NPS, therefore, show ultrastructural abnormalities including focal or diffuse irregular thickening of GBM with occasional regions of membrane discontinuity (“moth-eaten” appearance) (8, 9). However, little is known about the epidermal base- ment membrane (EBM). This study evaluated 2 families with NPS who were heterozygous for the splice-site mutations in LMX1B. We analysed the EBM in these families with NPS using electron microscopic and im- munohistochemical techniques. Acta Derm Venereol 2019; 99: 1110–1115. Corr: Satoru Shinkuma, Division of Dermatology, Niigata University Gra- duate School of Medical and Dental Sciences, 1-757, Asahimachi-dori, Chuo-Ku, Niigata, 951-8510, Japan. *E-mail: [email protected]. ac.jp N ail-patella syndrome (NPS; OMIM #161200) is characterized by nail dysplasia and skeletal ano- malies, such as aplastic or hypoplastic patella, elbow abnormalities, and iliac horn (1). The disease is an autosomal dominant disorder caused by a heterozygous loss-of-function mutation in the LMX1B gene (OMIM #602575), encoding a member of the LIM homeobox transcription factor 1β, LMXIB (2). LMX1B functions as a transcription factor and is essential for the normal development of dorsal limb structures, the glomerular basement membrane (GBM), anterior segment of the doi: 10.2340/00015555-3318 Acta Derm Venereol 2019; 99: XX–XX MATERIALS AND METHODS The medical ethics committee of Hokkaido University approved all the studies described herein. The study was conducted according to the principles of the Declaration of Helsinki. Written informed consent was obtained from the participants and/or their parents before the study procedures were conducted. Patients Two families with NPS were enrolled in this study. Family 1 was referred to us with nail deformities since birth. The affected family members were a mother (I-2), 9-year-old boy (II-1), 7-year-old twin sisters (II-2 and II-3), and 7-month-old younger brother (II-4) (Fig. 1a). Their thumbnails exhibited dysplasia (Fig. 1b–e). They also had triangular lunulae on their index, middle and ring fingers. The creases of the skin overlying the distal interphalangeal joints of their fingers were missing (Fig. 1f). This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.