Intrafamiliar clinical variability of circumferential skin creases Kunze type caused by a novel heterozygous mutation of N‐terminal TUBB gene. Issue 6 (11th April 2018) - Dentici, M.L.
Abstract : Circumferential skin creases Kunze type (CSC‐KT; OMIM 156610, 616734) is a rare disorder characterized by folding of excess skin, which leads to ringed creases, known as Michelin Tire Baby Syndrome (MTBS). CSC‐KT patients also exhibit facial dysmorphism, growth retardation, intellectual disability (ID) and multiple congenital malformations. Recently, 2 heterozygous mutations in TUBB gene and 4 mutations (both homozygous and heterozygous) in MAPRE2 gene were identified in 3 and 4 CSC‐KT patients, respectively. In the 3 TUBB gene‐related CSC‐KT patients, all mutations fall in the N‐terminal gene domain and were de novo. Mutations in the C‐terminal of TUBB gene have been associated to microcephaly and structural brain malformation, in the absence of CSC‐KT features. We report a 9‐year‐old boy with a diagnosis of CSC‐KT based on MTBS, facial dysmorphism, microcephaly, severe ID, cortical atrophy and corpus callosum hypoplasia. Sanger sequencing identified a novel heterozygous c.218T>C (p.Met73Thr) mutation in the N‐terminal of TUBB gene, that was inherited from the mother affected by isolated MTBS. This is the first report of inherited TUBB gene‐related CSC‐KT resulting from a novel heterozygous mutation in the N‐terminal domain. Present data support the role of TUBB mutations in CSC‐KT and definitely includes CSC‐KT syndrome within the tubulinopathies. Abstract :