A splice site mutation in HERC1 leads to syndromic intellectual disability with macrocephaly and facial dysmorphism: Further delineation of the phenotypic spectrum.
We report on a sib pair of Indian origin presenting with intellectual disability, dysmorphism, and macrocephaly. Exome sequencing revealed a homozygous splice site HERC1 mutation in both probands. Functional analysis revealed use of an alternate splice site resulting in formation of a downstream stop codon and nonsense mediated decay. In the light of recent reports of HERC1 mutations in two families with a similar phenotypic presentation, this report reiterates the pathogenic nature and clinical consequences of HERC1 disruption. © 2016 Wiley Periodicals, Inc.
Department of Medical Genetics, Nizam's Institute of Medical Sciences, Hyderabad, India.|Division of Diagnostics, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Shagun
S
Aggarwal
Division of Diagnostics, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Aneek Das
AD
Bhowmik
MedGenome Labs, Bangalore, India.
Vedam L
VL
Ramprasad
MedGenome Labs, Bangalore, India.
Sakthivel
S
Murugan
Division of Diagnostics, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Ashwin
A
Dalal
D002648:Child; D002675:Child, Preschool; D005145:Face / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D058627:Megalencephaly / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
D020662:Guanine Nucleotide Exchange Factors; D022821:RNA Splice Sites; C102169:HERC1 protein, human; D044767:Ubiquitin-Protein Ligases
HERC1; exome sequencing; intellectual disability; macrocephaly