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Expanding the phenotype of intellectual disability caused by HIVEP2 variants
Author(s) -
Goldsmith Heidi,
Wells Anna,
Sá Maria J. N.,
Williams Mark,
Heussler Helen,
Buckman Melissa,
Pfundt Rolph,
Vries Bert B. A.,
Goel Himanshu
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.61271
Subject(s) - intellectual disability , hypotonia , exome sequencing , genetics , phenotype , microcephaly , biology , angelman syndrome , exome , genotype , genotype phenotype distinction , bioinformatics , gene
De novo pathogenic variants in the human immunodeficiency virus enhancer type I binding protein 2 ( HIVEP2 ) gene, a large transcription factor predominantly expressed in the brain have previously been associated with intellectual disability (ID) and dysmorphic features in nine patients. We describe the phenotype and genotype of two additional patients with novel de novo pathogenic HIVEP2 variants, who have previously unreported features, including hyperphagia and Angelman‐like features. Exome sequencing was utilized in the investigation of the patients who had previously incurred a rigorous genetic workup for their neurodevelopmental delay, and in whom no genetic cause had been detected. Information pertaining to phenotype and genotype for new patients was collated along with data from previous reports, showing that the phenotypic spectrum of patients with HIVEP2 variants is broader than first noted. Additional characteristics are: an increased body mass index; and features of Angelman‐like syndromes including: ID, limited speech, post‐natal microcephaly, and hypotonia. Dysmorphic features vary between patients. As yet, no clear association between the type of gene aberration and phenotype can be concluded. HIVEP2 ‐related ID needs to be considered in the differential diagnosis of patients with Angelman‐like phenotypes and hyperphagia, and whole‐exome sequencing should be considered in the genetic diagnostic armamentarium for patients with ID of inconclusive etiology.