title: A Japanese child with geleophysic dysplasia caused by a novel mutation of FBN1.
abstract: Geleophysic dysplasia (GD) is a rare disorder characterized by severe short stature, short hands and feet, limited joint mobility, skin thickening, characteristic facial features (e.g., a "happy" face), and cardiac valvular disorders that often result in an early death. The genes ADAMTSL2 (a disintegrin-like and metalloprotease with thrombospondin type 1 motif-like 2) and FBN1 (fibrillin 1) were recently identified as causative genes for GD. Here, we describe a 10-year-old Japanese female with GD who was born to non-consanguineous parents. At the age of 11 months, she was referred to our hospital because of very short stature for her age (-4.4 standard deviations of the age-matched value) and a "happy" face with full cheeks, a shortened nose, hypertelorism, and a long and flat philtrum, characteristic of GD. Her hands and feet were small, her skin was thickened, and her joint mobility was generally limited. She had cardiac valvular disorders and history of recurrent respiratory failure. Mutation analysis revealed no abnormalities in ADAMTSL2. However, analysis of FBN1 revealed a novel heterozygous mutation (c.5161T>T/G) in exon 41, which encodes transforming growth factor-β-binding protein-like domain 5 (TB5). GD is an extremely rare disorder and, to our knowledge, only one case of GD with an FBN1 mutation has been reported in Japan. Similar to the previously reported cases of GD, the mutation in the current patient was located in the TB5 domain, which suggests that abnormalities in this domain of FBN1 are responsible for GD.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Lee
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Yo
authors.initials: Y
authors.lastname: Okizuka
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hamahira
authors.forename: Noriko
authors.initials: N
authors.lastname: Kusunoki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Awano
authors.forename: Mariko
authors.initials: M
authors.lastname: Yagi
authors.forename: Norio
authors.initials: N
authors.lastname: Sakai
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D044466:Asian People; D001848:Bone Diseases, Developmental / Q000235:genetics* / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D007564:Japan; D017880:Limb Deformities, Congenital / Q000235:genetics* / Q000473:pathology; D008840:Microfilament Proteins / Q000235:genetics*; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines