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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.

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  • Authors+Show Affiliations

    ,

    Dept. of Clinical Genetics, Odense University Hospital, Odense, Denmark. Electronic address: Anne.kroeigaard@rsyd.dk.

    ,

    Dept. of Endocrinology, Odense University Hospital, Odense, Denmark.

    ,

    Dept. of Clinical Genetics, Odense University Hospital, Odense, Denmark.

    ,

    Dept. of Clinical Genetics, Odense University Hospital, Odense, Denmark.

    Dept. of Clinical Genetics, Odense University Hospital, Odense, Denmark.

    Source

    Bone 92: 2016 11 pg 145-149

    MeSH

    Adolescent
    Bone Density
    Dwarfism
    Female
    Fetal Growth Retardation
    Humans
    Male
    Microcephaly
    Middle Aged
    Mutation
    Osteochondrodysplasias
    RNA, Small Nuclear
    Spliceosomes
    Young Adult

    Pub Type(s)

    Case Reports
    Journal Article

    Language

    eng

    PubMed ID

    27591150

    Citation

    Krøigård, Anne Bruun, et al. "Bone Structure in Two Adult Subjects With Impaired Minor Spliceosome Function Resulting From RNU4ATAC Mutations Causing Microcephalic Osteodysplastic Primordial Dwarfism Type 1 (MOPD1)." Bone, vol. 92, 2016, pp. 145-149.
    Krøigård AB, Frost M, Larsen MJ, et al. Bone structure in two adult subjects with impaired minor spliceosome function resulting from RNU4ATAC mutations causing microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1). Bone. 2016;92:145-149.
    Krøigård, A. B., Frost, M., Larsen, M. J., Ousager, L. B., & Frederiksen, A. L. (2016). Bone structure in two adult subjects with impaired minor spliceosome function resulting from RNU4ATAC mutations causing microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1). Bone, 92, pp. 145-149. doi:10.1016/j.bone.2016.08.023.
    Krøigård AB, et al. Bone Structure in Two Adult Subjects With Impaired Minor Spliceosome Function Resulting From RNU4ATAC Mutations Causing Microcephalic Osteodysplastic Primordial Dwarfism Type 1 (MOPD1). Bone. 2016;92:145-149. PubMed PMID: 27591150.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Bone structure in two adult subjects with impaired minor spliceosome function resulting from RNU4ATAC mutations causing microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1). AU - Krøigård,Anne Bruun, AU - Frost,Morten, AU - Larsen,Martin Jakob, AU - Ousager,Lilian Bomme, AU - Frederiksen,Anja Lisbeth, Y1 - 2016/08/31/ PY - 2016/01/05/received PY - 2016/08/22/revised PY - 2016/08/30/accepted PY - 2016/9/4/pubmed PY - 2018/1/4/medline PY - 2016/9/4/entrez KW - HR-pQCT KW - MOPD1 KW - Minor spliceosome KW - Osteodysplasia KW - RNU4ATAC KW - Taybi-Linder syndrome SP - 145 EP - 149 JF - Bone JO - Bone VL - 92 N2 - 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. SN - 1873-2763 UR - https://www.unboundmedicine.com/medline/citation/27591150/Bone_structure_in_two_adult_subjects_with_impaired_minor_spliceosome_function_resulting_from_RNU4ATAC_mutations_causing_microcephalic_osteodysplastic_primordial_dwarfism_type_1__MOPD1__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S8756-3282(16)30243-5 DB - PRIME DP - Unbound Medicine ER -