Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia

Barraza-Garcia, J., Rivera-Pedroza, C. I., Hisado-Oliva, A., Belinchon-Martinez, A., Sentchordi-Montane, L., Duncan, E. L., Clark, G. R., del Pozo, A., Ibanez-Garikano, K., Offiah, A., Prieto-Matos, P., Cormier-Daire, V. and Heath, K. E. (2017) Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia. Clinical Genetics, . doi:10.1111/cge.12964


Author Barraza-Garcia, J.
Rivera-Pedroza, C. I.
Hisado-Oliva, A.
Belinchon-Martinez, A.
Sentchordi-Montane, L.
Duncan, E. L.
Clark, G. R.
del Pozo, A.
Ibanez-Garikano, K.
Offiah, A.
Prieto-Matos, P.
Cormier-Daire, V.
Heath, K. E.
Title Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia
Journal name Clinical Genetics   Check publisher's open access policy
ISSN 1399-0004
0009-9163
Publication date 2017-02-22
Sub-type Article (original research)
DOI 10.1111/cge.12964
Open Access Status Not yet assessed
Total pages 8
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell Publishing
Collection year 2018
Language eng
Formatted abstract
Processing of Precursor 1 (POP1) is a large protein common to the ribonuclease-mitochondrial RNA processing (RNase-MRP) and RNase-P (RMRP) endoribonucleoprotein complexes. Although its precise function is unknown, it appears to participate in the assembly or stability of both complexes. Numerous RMRP mutations have been reported in individuals with cartilage-hair hypoplasia (CHH) but, to date, only three POP1 mutations have been described in two families with features similar to anauxetic dysplasia (AD). We present two further individuals, one with severe short stature and a relatively mild skeletal dysplasia and another in whom AD was suspected. Biallelic POP1 mutations were identified in both. A missense mutation and a novel single base deletion were detected in proband 1, p.[Pro582Ser]:[Glu870fs*5]. Markedly reduced abundance of RMRP and elevated levels of pre5.8s rRNA was observed. In proband 2, a homozygous novel POP1 mutation was identified, p.[(Asp511Tyr)];[(Asp511Tyr)]. These two individuals show the phenotypic extremes in the clinical presentation of POP1-dysplasias. Although CHH and other skeletal dysplasias caused by mutations in RMRP or POP1 are commonly cited as ribosomal biogenesis disorders, recent studies question this assumption. We discuss the past and present knowledge about the function of the RMRP complex in skeletal development.
Keyword Anauxetic dysplasia
Bone
POP1
RMRP
Skeletal dysplasia
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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UQ Diamantina Institute Publications
 
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