Acromesomelic Dysplasia With Homozygosity for a Likely Pathogenic BMPR1B Variant: Postaxial Polydactyly as a Novel Clinical Finding.

Autor: Abdelrazek IM; Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt., Knaus A; Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, University Hospital Bonn, Bonn, Germany., Javanmardi B; Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, University Hospital Bonn, Bonn, Germany., Krawitz PM; Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, University Hospital Bonn, Bonn, Germany., Horn D; Institute of Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany., Abdalla EM; Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt., Kumar S; Institute of Human Genetics, Medical Faculty, University of Bonn, University Hospital Bonn, Bonn, Germany.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2024 Oct; Vol. 12 (10), pp. e70023.
DOI: 10.1002/mgg3.70023
Abstrakt: Background: Acromesomelic chondrodysplasias are a rare subgroup of the clinically and genetically heterogeneous osteochondrodysplasias that are characterised by abnormalities in the limb development and short stature. Here, we report a 2-year-old boy, offspring of consanguineous parents, with acromesomelic dysplasia and postaxial polydactyly in which exome sequencing identified a novel homozygous missense variant in BMPR1B. The patient showed skeletal malformation of both hands and feet that included complex brachydactyly with the thumbs most severely affected, postaxial polydactyly of both hands, shortened toes as well as a bilateral hypoplasia of the fibula.
Methods: Whole trio exome sequencing was conducted to identify potential genetic variants in the patient.
Results: The analysis identified the biallelic variant NM_001203.3:c.821A > G;p.(Gln274Arg) in BMPR1B, a gene encoding bone morphogenetic protein receptor 1B.
Conclusion: The skeletal phenotype can be brought in line with the phenotypes of previously reported cases of BMPR1B-associated chondrodysplasias. However, the postaxial polydactyly described here is a novel clinical finding in a BMPR1B-related case; notably, it has previously been reported in other acromesomelic dysplasia cases caused by homozygous pathogenic variants in GDF5-a gene which encodes for growth differentiation factor 5, a high-affinity ligand to BMPR1B.
(© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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