Mutations in two large pedigrees highlight the role of ZNF711 in X-linked intellectual disability

• Published in: Gene Vol. 605; pp. 92 - 98
• Main Authors: van der Werf, Ilse M., Van Dijck, Anke, Reyniers, Edwin, Helsmoortel, Céline, Kumar, Ajay Anand, Kalscheuer, Vera M., de Brouwer, Arjan PM, Kleefstra, Tjitske, van Bokhoven, Hans, Mortier, Geert, Janssens, Sandra, Vandeweyer, Geert, Kooy, R. Frank
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.03.2017
• Subjects: Adolescent; Adult; Articulation Disorders - diagnosis; Articulation Disorders - genetics; Articulation Disorders - physiopathology; Autism Spectrum Disorder - diagnosis; Autism Spectrum Disorder - genetics; Autism Spectrum Disorder - physiopathology; Base Sequence; Child; cognition; DNA-Binding Proteins - genetics; Exome; Female; Gene Expression; genes; Genes, X-Linked; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Intellectual Disability - physiopathology; Male; males; Middle Aged; MRX65; Mutation; patients; Pedigree; Phenotype; Sequence Analysis, DNA; Severity of Illness Index; speech; XLID; ZNF711; CADD; KDM5C; ICD-10; RNA; CDCA7; LRRC4; THY1; REVEL; CNN3; PHF8; PQBP1; STR; PTBP1; ARID; HEK293; UTR; ZNF81; ExAC; GRCh37/hg19; SNP; ZNF41; PIEZO2; cDNA; FYN; ID; ADID; XLID; IQ; SYP; YWHAZ; TCGA; CAMKMT; MRX65; (q)PCR; DNA; CHDH; TAF6; ZNF711; HPRT1; ZNF674
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2016.12.013

Intellectual disability (ID) affects approximately 1–2% of the general population and is characterized by impaired cognitive abilities. ID is both clinically as well as genetically heterogeneous, up to 2000 genes are estimated to be involved in the emergence of the disease with various clinical presentations. For many genes, only a few patients have been reported and causality of some genes has been questioned upon the discovery of apparent loss-of-function mutations in healthy controls. Description of additional patients strengthens the evidence for the involvement of a gene in the disease and can clarify the clinical phenotype associated with mutations in a particular gene. Here, we present two large four-generation families with a total of 11 males affected with ID caused by mutations in ZNF711, thereby expanding the total number of families with ID and a ZNF711 mutation to four. Patients with mutations in ZNF711 all present with mild to moderate ID and poor speech accompanied by additional features in some patients, including autistic features and mild facial dysmorphisms, suggesting that ZNF711 mutations cause non-syndromic ID. •Mutations in ZNF711 cause non-syndromic X-linked intellectual disability.•Patients present with mild to moderate ID and poor speech•Impaired function of ZNF711 causes differential expression of a limited set of genes.