Open AccessIdentification of Novel and Recurrent <b><i>RMRP</i></b> Variants in a Series of Brazilian Patients with Cartilage-Hair Hypoplasia: McKusick Syndrome
Author(s) -
Maria E.S. Gomes,
Luiza Calatrava Paternostro,
Valeria R. Moura,
Deborah Antunes,
Ernesto R. Caffarena,
Dafne Dain Gandelman Horovitz,
Maria Teresa Vieira Sanseverino,
Gabriela Ferraz Leal,
Têmis Maria Félix,
Denise Pontes Cavalcanti,
Juan Clinton Llerena,
Sayonara Gonzalez
Publication year - 2019
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000501892
Subject(s) - genetics , dysplasia , phenotype , exon , medicine , gene , biology
Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder caused by pathogenic variants of the RMRP gene and characterized by metaphyseal bone dysplasia associated with hypotrichosis, immunodeficiency, and predisposition to malignancy. However, the genotype-phenotype correlation in CHH is not well understood. Here, we report a single country cohort of 23 Brazilian patients with clinical and radiological features consistent with CHH. We found 23 different pathogenic variants in the RMRP gene - 12 novel and 11 previously described in the literature. Interestingly, the most frequent Finnish pathogenic variant related to CHH (g.71A>G) was not found in our cohort. In contrast, more than 50% of the patients carried the rare g.196C>T variant suggesting a possible founder effect in the Brazilian population. In silico analysis showed that pathogenic variants occurred either in the regions conserved in mammalian species or within essential domains for the ribonucleoprotein complex. Pathogenicity prediction studies can improve the understanding of how these variants affect RNA.