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- Title
De novo apparent loss-of-function mutations in <italic>PRR12</italic> in three patients with intellectual disability and iris abnormalities.
- Authors
Leduc, Magalie S.; Mcguire, Marianne; Madan-Khetarpal, Suneeta; Ortiz, Damara; Hayflick, Susan; Keller, Kory; Eng, Christine M.; Yang, Yaping; Bi, Weimin
- Abstract
<italic>PRR12</italic> encodes a proline-rich protein nuclear factor suspected to be involved in neural development. Its nuclear expression in fetal brains and in the vision system supports its role in brain and eye development more specifically. However, its function and potential role in human disease has not been determined. Recently, a de novo t(10;19) (q22.3;q13.33) translocation disrupting the <italic>PRR12</italic> gene was detected in a girl with intellectual disability and neuropsychiatric alterations. Here we report on three unrelated patients with heterozygous de novo apparent loss-of-function mutations in <italic>PRR12</italic> detected by clinical whole exome sequencing: c.1918G>T (p.Glu640*), c.4502_4505delTGCC (p.Leu1501Argfs*146) and c.903_909dup (p.Pro304Thrfs*46). All three patients had global developmental delay, intellectual disability, eye and vision abnormalities, dysmorphic features, and neuropsychiatric problems. Eye abnormalities were consistent among the three patients and consisted of stellate iris pattern and iris coloboma. Additional variable clinical features included hypotonia, skeletal abnormalities, sleeping problems, and behavioral issues such as autism and anxiety. In summary, we propose that haploinsufficiency of <italic>PRR12</italic> is associated with this novel multisystem neurodevelopmental disorder.
- Subjects
GENETIC mutation; PEOPLE with intellectual disabilities; IRIS (Eye) diseases; PROLINE; PROTEIN expression
- Publication
Human Genetics, 2018, Vol 137, Issue 3, p257
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-018-1877-0