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Expansion of the clinical phenotype associated with mutations in activity-dependent neuroprotective protein
  1. Matthew F Pescosolido1,2,3,4,
  2. Matthew Schwede1,
  3. Ashley Johnson Harrison3,4,
  4. Michael Schmidt1,4,
  5. Ece D Gamsiz1,3,4,
  6. Wendy S Chen5,
  7. John P Donahue5,
  8. Natasha Shur6,
  9. Beth A Jerskey3,4,
  10. Chanika Phornphutkul7,
  11. Eric M Morrow1,3,4
  1. 1Department of Molecular Biology, Cell Biology and Biochemistry, Providence, Rhode Island, USA
  2. 2Lab for Molecular Medicine, Institute for Brain Science, Brown University, Providence, Rhode Island, USA
  3. 3Developmental Disorders Genetics Research Program, Emma Pendleton Bradley Hospital and Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, East Providence, Rhode Island, USA
  4. 4Rhode Island Consortium of Autism Research and Treatment (RI-CART), Providence, Rhode Island, USA
  5. 5Division of Ophthalmology, Department of Surgery, Alpert Medical School of Brown University, Providence, Rhode Island, USA
  6. 6Department of Pediatrics, Division of Genetics, Children's Hospital at Albany Medical Center, Albany, New York, USA
  7. 7Department of Pediatrics, Division of Human Genetics, Rhode Island Hospital and Brown University, Providence, Rhode Island, USA
  1. Correspondence to Dr Eric M Morrow, Brown University, Lab for Molecular Medicine, 70 Ship Street, Providence, RI 02912, USA; eric_morrow{at}

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Activity-dependent neuroprotective protein (ADNP) is a highly conserved transcription factor comprised of nine-zinc finger domains and a homeobox domain.1 ,2 It is highly expressed prenatally during critical stages of embryonic brain development.3 Knockout (KO) mouse embryos demonstrate severe neurodevelopmental morphological profiles.4 Although the ADNP KO is lethal, heterozygous embryos demonstrate typical embryogenesis yet display a neurodevelopmental delay phenotype including decreased neuronal survival.3 ,5

Exome sequencing in the Simons Simplex Collection autism dataset identified ADNP mutations as a putative autism gene candidate.6 ,7 Helsmoortel et al8 recently reported 10 individuals with autism spectrum disorder (ASD) and mutations in exon 5 of the ADNP gene, nine of which were confirmed de novo. These patients also exhibited intellectual disability (ID) and dysmorphic features such as a prominent forehead. Mutations in the ADNP gene are estimated to be present in at least 0.17% of ASD cases. The current report further expands the ADNP phenotype to include abnormalities in the developing visual system (such as eye movement abnormalities and cortical visual impairment). We advise appropriate screening of eye movement and visual symptoms by clinicians in patients who have mutations in ADNP.

The 6-year-old patient was the first child born to healthy non-consanguineous parents. Pregnancy was notable for placenta previa and early dilation and effacement of the cervix 3 weeks prior to delivery. The patient was born at 40 weeks via C-section secondary to failure to progress and maternal (i.e. maternal hypertension) hypertension weighing 6 pounds 14 ounces. She had a short stay in the neonatal intensive care unit (NICU) for breathe holding and feeding problems. She was also hospitalised at 6 weeks for an acute life-threatening event of multiple cyanotic episodes thought to be due to breath holding. Our patient has been diagnosed with hypotonia and mixed developmental …

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