Expanding phenotype with severe midline brain anomalies and missense variant supports a causal role forFOXA2in 20p11.2 deletion syndrome
| Autor: | Melissa Racobaldo, Amarilis Sanchez-Valle, Erin Torti, Jane Juusola, Katrina M. Dipple, Jennifer N. Dines, Gisele E. Ishak, Christine M. Disteche, Kirsty McWalter, Dan Doherty, Whitney Neufeld-Kaiser, Yajuan J. Liu, Hannah M. Tully, Taylor Sawyer |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Chromosomes Human Pair 20 Mutation Missense Piriform Cortex Constriction Pathologic 030105 genetics & heredity Hypopituitarism 03 medical and health sciences Biliary atresia Genetics medicine Humans Missense mutation Genetic Predisposition to Disease Genetics (clinical) business.industry Organ dysfunction Infant Newborn Brain medicine.disease Phenotype Hydrocephalus 030104 developmental biology Aqueductal stenosis Dysplasia Hepatocyte Nuclear Factor 3-beta Chromosome Deletion medicine.symptom business Heterotaxy |
| Zdroj: | American Journal of Medical Genetics Part A. |
| ISSN: | 1552-4833 1552-4825 |
| DOI: | 10.1002/ajmg.a.61281 |
| Popis: | Rare individuals with 20p11.2 proximal deletions have been previously reported, with a variable phenotype that includes heterotaxy, biliary atresia, midline brain defects associated with panhypopituitarism, intellectual disability, scoliosis, and seizures. Deletions have ranged in size from 277 kb to 11.96 Mb. We describe a newborn with a de novo 2.7 Mb deletion of 20p11.22p11.21 that partially overlaps previously reported deletions and encompasses FOXA2. Her clinical findings further expand the 20p11.2 deletion phenotype to include severe midline cranial and intracranial defects such as aqueductal stenosis with hydrocephalus, mesencephalosynapsis with diencephalic-mesencephalic junction dysplasia, and pyriform aperture stenosis. We also report one individual with a missense variant in FOXA2 who had abnormal glucose homeostasis, panhypopituitarism, and endodermal organ dysfunction. Together, these findings support the critical role of FOXA2 in panhypopituitarism and midline defects. |
| Databáze: | OpenAIRE |
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