Phenotypic Variability in a Family with Acrodysostosis Type 2 Caused by a Novel PDE4D Mutation Affecting the Serine Target of Protein Kinase-A Phosphorylation
| Autor: | Julia Gesing, Franz Wolfgang Hirsch, Chrystel Leroy, Caroline Silve, Wieland Kiess, Julia Hoppmann, Roland Pfäffle, Volker Schuster, Astrid Bertsche |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Acrodysostosis Endocrinology Diabetes and Metabolism phosphodiesterase 4D Mutation Missense Mothers Case Report skeletal dysplasia medicine.disease_cause Osteochondrodysplasias Short stature Genetic analysis Nuclear Family 03 medical and health sciences Endocrinology Intellectual Disability medicine Serine Missense mutation Humans Phosphorylation Genetics Mutation business.industry Brachydactyly inactivating parathyroid hormone/parathyroid hormone related protein signalling disorder brachydactyly inactivating parathyroid hormone/parathyroid hormone related protein signalling disorder phosphodiesterase 4D Dysostoses medicine.disease Phenotype Cyclic AMP-Dependent Protein Kinases Hypoplasia Cyclic Nucleotide Phosphodiesterases Type 4 030104 developmental biology Amino Acid Substitution Child Preschool Pediatrics Perinatology and Child Health Female medicine.symptom business |
| Zdroj: | Journal of Clinical Research in Pediatric Endocrinology Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid |
| ISSN: | 1308-5735 1308-5727 |
| Popis: | Acrodysostosis is a very rare congenital multisystem condition characterized by skeletal dysplasia with severe brachydactyly, midfacial hypoplasia, and short stature, varying degrees of intellectual disability, and possible resistance to multiple G protein-coupled receptor signalling hormones. Two distinct subtypes are differentiated: acrodysostosis type 1 resulting from defects in protein kinase type 1-α regulatory subunit and acrodysostosis type 2 caused by mutations in phosphodiesterase 4D (PDE4D). Most cases are sporadic. We report on a rare multigenerational familial case of acrodysostosis type 2 due to a novel autosomal dominantly inherited PDE4D mutation. A 3.5-year-old boy presented with short stature, midfacial hypoplasia, severe brachydactyly, developmental delay, and behavioural problems. Laboratory investigations revealed mild thyrotropin resistance. His mother shared some characteristic features, such as midfacial hypoplasia and severe brachydactyly, but did not show short stature, intellectual disability or hormonal resistance. Genetic analysis identified the identical, novel heterozygous missense mutation of the PDE4D gene c.569C>T (p.Ser190Phe) in both patients. This case illustrates the significant phenotypic variability of acrodysostosis even within one family with identical mutations. Hence, a specific clinical diagnosis of acrodysostosis remains challenging because of great interindividual variability and a substantial overlap of the two subtypes as well as with other related Gsα-cAMP-signalling-linked disorders. |
| Databáze: | OpenAIRE |
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