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Expanding phenotype with severe midline brain anomalies and missense variant supports a causal role for FOXA2 in 20p11.2 deletion syndrome
Author(s) -
Dines Jennifer N.,
Liu Yajuan J.,
NeufeldKaiser Whitney,
Sawyer Taylor,
Ishak Gisele E.,
Tully Hannah M.,
Racobaldo Melissa,
SanchezValle Amarilis,
Disteche Christine M.,
Juusola Jane,
Torti Erin,
McWalter Kirsty,
Doherty Dan,
Dipple Katrina M.
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61281
Subject(s) - aqueductal stenosis , missense mutation , phenotype , biology , ventriculomegaly , foxa2 , encephalocele , microcephaly , microphthalmia , hydrocephalus , haploinsufficiency , genetics , atresia , pathology , anatomy , medicine , gene , pregnancy , fetus , radiology , gene expression
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.