De novo apparent loss-of-function mutations in PRR12 in three patients with intellectual disability and iris abnormalities

Magalie S. Leduc, Marianne Mcguire, Suneeta Madan-Khetarpal, Damara Ortiz, Susan Hayflick, Kory Keller, Christine M. Eng, Yaping Yang, Weimin Bi

Research output: Contribution to journalArticle

Abstract

PRR12 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 PRR12 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 PRR12 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 PRR12 is associated with this novel multisystem neurodevelopmental disorder.

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalHuman Genetics
Volume137
Issue number3
DOIs
StatePublished - Mar 1 2018

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Iris
Eye Abnormalities
Intellectual Disability
Mutation
Coloboma
Exome
Haploinsufficiency
Muscle Hypotonia
Brain
Autistic Disorder
Nuclear Proteins
Proline
Anxiety
Genes

ASJC Scopus subject areas

  • Medicine(all)

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De novo apparent loss-of-function mutations in PRR12 in three patients with intellectual disability and iris abnormalities. / Leduc, Magalie S.; Mcguire, Marianne; Madan-Khetarpal, Suneeta; Ortiz, Damara; Hayflick, Susan; Keller, Kory; Eng, Christine M.; Yang, Yaping; Bi, Weimin.

In: Human Genetics, Vol. 137, No. 3, 01.03.2018, p. 257-264.

Research output: Contribution to journalArticle

Leduc, MS, Mcguire, M, Madan-Khetarpal, S, Ortiz, D, Hayflick, S, Keller, K, Eng, CM, Yang, Y & Bi, W 2018, 'De novo apparent loss-of-function mutations in PRR12 in three patients with intellectual disability and iris abnormalities', Human Genetics, vol. 137, no. 3, pp. 257-264. https://doi.org/10.1007/s00439-018-1877-0
Leduc, Magalie S. ; Mcguire, Marianne ; Madan-Khetarpal, Suneeta ; Ortiz, Damara ; Hayflick, Susan ; Keller, Kory ; Eng, Christine M. ; Yang, Yaping ; Bi, Weimin. / De novo apparent loss-of-function mutations in PRR12 in three patients with intellectual disability and iris abnormalities. In: Human Genetics. 2018 ; Vol. 137, No. 3. pp. 257-264.
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