HERC1 mutations in idiopathic intellectual disability.
HERC1 is a member of HERC protein family of ubiquitin ligases and is a negative regulator of the mTOR pathway. It is also a guanine nucleotide exchange factor for ARF and Rab family GTPases. Biallelic mutations in HERC1 were recently shown to cause a human phenotype with overgrowth and intellectual disability as main features. Herein we describe clinical features in another patient with homozygous novel mutation in HERC1. Moderate to severe intellectual disability, hypotonia, macrocephaly, tall stature, and facial features appear as main clinical features of the condition. Kyphoscoliosis and seizures frequently accompany and autistic features might be another feature as recent studies also implicate. HERC1 mutations should be considered in differential diagnosis of severe intellectual disability and behavioural problems, particularly in patients testing negative for fragile X and KANSL1 mutations.
Hacettepe University, Faculty of Medicine, Department of Pediatric Genetics, Ankara, Turkey. Electronic address: geutine@hacettepe.edu.tr.
G Eda
GE
Utine
Hacettepe University, Faculty of Medicine, Department of Medical Genetics, Ankara, Turkey.
Ekim Z
EZ
Taşkıran
Hacettepe University, Faculty of Medicine, Department of Medical Genetics, Ankara, Turkey.
Can
C
Koşukcu
Hacettepe University, Faculty of Medicine, Department of Medical Genetics, Ankara, Turkey.
Beren
B
Karaosmanoğlu
Hacettepe University, Faculty of Medicine, Department of Medical Genetics, Ankara, Turkey.
Naz
N
Güleray
Hacettepe University, Faculty of Medicine, Department of Pediatric Genetics, Ankara, Turkey.
Özlem Akgün
ÖA
Doğan
Hacettepe University, Faculty of Medicine, Department of Pediatric Genetics, Ankara, Turkey.
P Özlem Şimşek
PÖ
Kiper
Hacettepe University, Faculty of Medicine, Department of Pediatric Genetics, Ankara, Turkey.
Koray
K
Boduroğlu
Hacettepe University, Faculty of Medicine, Department of Medical Genetics, Ankara, Turkey.
Mehmet
M
Alikaşifoğlu
D002675:Child, Preschool; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009154:Mutation; D044767:Ubiquitin-Protein Ligases
D020662:Guanine Nucleotide Exchange Factors; C102169:HERC1 protein, human; D044767:Ubiquitin-Protein Ligases
Autism; HERC1; Intellectual disability; Overgrowth