Two mutations in IFITM5 causing distinct forms of osteogenesis imperfecta.
The IFITM5 gene has recently been found to be mutated in patients with autosomal dominant osteogenesis imperfecta (OI) type V. This form of OI is characterized by distinctive clinical manifestations, including hyperplastic callus formation at the site of fractures, calcification of the interosseous membrane of the forearm, and dislocation of the head of the radius. Notably, in spite of the fact that a considerable number of patients with IFITM5 mutations have been identified, to date all of them have been shown to have the same heterozygous mutation (c.-14C>T). Herein, we describe one patient with a de novo c.119C>T heterozygous mutation in IFITM5, which predicts p.Ser40Leu, and another with the recurrent c.-14C>T transition that was also apparently de novo. While the patient with the p.Ser40Leu mutation had none of the typical signs of OI type V and was diagnosed with limb shortening at prenatal stages, the patient with the c.-14C>T mutation developed hyperplastic calluses and had calcification of the forearm interosseous membrane. This study challenges the lack of allelic and clinical heterogeneity in IFITM5 mutations.
Unidad de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain; Cátedra de Genética Médica, Universidad Católica de San Antonio (UCAM), Murcia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
Encarna
E
Guillén-Navarro
María Juliana
MJ
Ballesta-Martínez
María
M
Valencia
Ana María
AM
Bueno
Victor
V
Martinez-Glez
Vanesa
V
López-González
Birute
B
Burnyte
Algirdas
A
Utkus
Pablo
P
Lapunzina
Victor L
VL
Ruiz-Perez
D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D011859:Radiography
C575746:IFITM5 protein, human; D008565:Membrane Proteins
BRIL; IFITM5; OI type V; bone development; osteogenesis imperfecta