title: A novel neurodevelopmental disorder associated with compound heterozygous variants in the huntingtin gene.
abstract: We report compound heterozygous variants in HTT, the gene encoding huntingtin, in association with an autosomal recessive neurodevelopmental disorder. Three siblings presented with severe global developmental delay since birth, central hypotonia progressing to spastic quadraparesis, feeding difficulties, dystonia (2/3 sibs), prominent midline stereotypies (2/3), bruxism (1/3), high myopia (2/3), and epilepsy (1/3). Whole exome sequencing identified compound heterozygous variants in HTT that co-segregated in the three affected sibs and were absent in an unaffected sib. There were no additional variants in other genes that could account for the reported phenotype. Molecular analysis of HTT should be considered, not just for Huntington's disease, but also in children with a Rett-like syndrome who test negative for known Rett and Rett-like syndrome genes.
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Lance H
authors.initials: LH
authors.lastname: Rodan
authors.affiliation: Division of Neurogenetics, Kennedy Krieger Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Division of Neurogenetics, Kennedy Krieger Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Fatemi
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Tammy
authors.initials: T
authors.lastname: Gillis
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Lucente
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.|Department of Genetics, Harvard Medical School, Boston, MA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Gusella
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Picker
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics*; D008297:Male; D009123:Muscle Hypotonia / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein