title: Bone structure in two adult subjects with impaired minor spliceosome function resulting from RNU4ATAC mutations causing microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1).
abstract: Microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1), or Taybi-Linder syndrome is characterized by distinctive skeletal dysplasia, severe intrauterine and postnatal growth retardation, microcephaly, dysmorphic features, and neurological malformations. It is an autosomal recessive disorder caused by homozygous or compound heterozygous mutations in the RNU4ATAC gene resulting in impaired function of the minor spliceosome. Here, we present the first report on bone morphology, bone density and bone microstructure in two adult MOPD1 patients and applied radiographs, dual energy X-ray absorptiometry, high-resolution peripheral quantitative computed tomography and biochemical evaluation. The MOPD1 patients presented with short stature, low BMI but normal macroscopic bone configuration. Bone mineral density was low. Compared to Danish reference data, total bone area, cortical bone area, cortical thickness, total bone density, cortical bone density, trabecular bone density and trabecular bone volume per tissue volume (BV/TV) were all low. These findings may correlate to the short stature and low body weight of the MOPD1 patients. Our findings suggest that minor spliceosome malfunction may be associated with altered bone modelling.
authors: Dept. of Clinical Genetics, Odense University Hospital, Odense, Denmark. Electronic address: Anne.kroeigaard@rsyd.dk.
authors: Anne Bruun
authors: AB
authors: Krøigård
authors: Dept. of Endocrinology, Odense University Hospital, Odense, Denmark.
authors: Morten
authors: M
authors: Frost
authors: Dept. of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors: Martin Jakob
authors: MJ
authors: Larsen
authors: Dept. of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors: Lilian Bomme
authors: LB
authors: Ousager
authors: Dept. of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors: Anja Lisbeth
authors: AL
authors: Frederiksen
mesh_terms: D000293:Adolescent; D015519:Bone Density / Q000235:genetics*; D004392:Dwarfism / Q000000981:diagnostic imaging* / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging* / Q000235:genetics*; D006801:Humans; D008297:Male; D008831:Microcephaly / Q000000981:diagnostic imaging* / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging* / Q000235:genetics*; D012342:RNA, Small Nuclear / Q000235:genetics*; D017381:Spliceosomes / Q000235:genetics*; D055815:Young Adult
chemical_list: D012342:RNA, Small Nuclear; C000590616:RNU4ATAC RNA, human
keywords: HR-pQCT; MOPD1; Minor spliceosome; Osteodysplasia; RNU4ATAC; Taybi-Linder syndrome