Transplanting <i>CY282</i> heterozygous livers is risky

Background: The Schmid type of metaphyseal chondrodysplasia (MCDS) is generally due to mutations in COL10A1 encoding for type X collagen of cartilage.Methods: We performed a study on the genes coding for the RNA components of RNase MRP (MRPR) and RNase P (H1RNA) among 20 patients with diagnosis of MCDS and no mutations in COL10A1.Results: Two patients were found to be homozygous for a base substitution G for A at nucleotide 70 of RMRP, which is the major mutation causing cartilage-hair hypoplasia.No pathogenic mutations were detected in H1RNA.Conclusion: Cartilage-hair hypoplasia diagnosis should be considered in patients with metaphyseal chondrodysplasia even in the absence of any extra-skeletal manifestations if no mutation in COL10A1 can be found and the family history is compatible with autosomal recessive inheritance.Correct diagnosis is important for genetic counselling and for proper follow up of the patients. The Schmid type of metaphyseal chondrodysplasia (MCDS, OMIM 156500) is characterised by short stature, bowed legs, coxa vara, and specific metaphyseal changes seen in radiographs. 1 2 Autosomal dominant mutations in COL10A1 (OMIM # 120110), which encodes for type X short chain non-fibrillar collagen of cartilage, have been identified in some patients with this phenotype.Most of the mutations reside in the carboxyterminal globular domain (CN1) while two mutations are in a putative signal peptide cleavage site.[3][4][5][6][7][8] Despite thorough mutation screening in COL10A1, no mutations have been identified in a number of MCDS patients.9 10 We have recently reported on 46 RMRP (OMIM # 157660) mutations causing recessively inherited cartilage-hair hypoplasia (CHH, OMIM # 250250), another type of metaphyseal chondrodysplasia.11 12 CHH is characterised clinically by short limbed short stature, hair hypoplasia, defective immunity, and haematological abnormalities, and radiographically by metaphyseal flaring and irregularity.13 14 The untranslated RMRP gene encodes the RNA component of the RNase mitochondrial RNA processing (MRP) complex.Normally, the RNase endoribonuclease MRP complex is involved in multiple cellular and mitochondrial functions but the functional impairment of the RMRP gene product that causes disease remains to be characterised.11 15 Although MCDS and CHH are separate disorders, phenotypes and metaphyseal changes in radiographs can resemble each other.As mutations in the COL10A1 gene explain only part of the MCDS cases, we first hypothesised that the RMRP genotype might play a role.In a search for RMRP mutations in 20 patients with diagnosis of MCDS and no mutations in COL10A1, we found two patients homozygous for the major mutation 70ARG.This finding has further initiated our screening in the same set of patients for mutations in H1RNA, a gene coding for the RNA component of RNase P, another endoribonuclease, which is structurally and functionally similar to RNase MRP. 15

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.