An X‐linked syndrome with severe neurodevelopmental delay, hydrocephalus, and early lethality caused by a missense variation in the OTUD5 gene
| Autor: | Abdul Halim Kassim, Erina Sasaki, Arndt Rolfs, Ronja Hotakainen, Peter Bauer, William Reardon, Kornelia Tripolszki, Catarina Pereira, Aida M. Bertoli-Avella |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Pediatrics medicine.medical_specialty Candidate gene Mutation Missense Disease 030105 genetics & heredity Asymptomatic 03 medical and health sciences Genes X-Linked Endopeptidases Intellectual disability Genetics medicine Humans Missense mutation Abnormalities Multiple Genetic Association Studies Genetics (clinical) Family Health Whole Genome Sequencing business.industry Infant Newborn Syndrome medicine.disease Hypotonia Pedigree Hydrocephalus 030104 developmental biology Neurodevelopmental Disorders Genes Lethal medicine.symptom business Ventriculomegaly |
| Zdroj: | Clinical Genetics. 99:303-308 |
| ISSN: | 1399-0004 0009-9163 |
| DOI: | 10.1111/cge.13873 |
| Popis: | We describe an X-linked syndrome in 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with intrauterine growth retardation, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. We performed genome sequencing in four individuals and identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals. OTUD5 was considered as a candidate gene based on two previous missense variants detected in patients with intellectual disability. In conclusion, we define a syndrome associated with OTUD5 defects and add compelling evidence of genotype-phenotype association. This finding ended the long diagnostic odyssey of this family. |
| Databáze: | OpenAIRE |
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