This report describes White-Sutton syndrome (WHSUS), a neurodevelopmental disorder that exhibits autosomal dominant inheritance. WHSUS is included in the phenotypic series for autosomal dominant intellectual disability by OMIM. The human gene implicated in this disease is POGZ (pogo transposable element with ZNF domain), which encodes a zinc finger protein containing a transposase domain at the C-terminus; it appears to play a role in mitotic cell cycle progression and mitotic chromosome segregation. There is a single orthologous gene in Drosophila, row, for which RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\row is also orthologous to three other zinc finger proteins in human, ZNF280C, ZNF280D, and ZNF280D.
The human POGZ gene has not been introduced into flies. POGZ has been give a high-confidence score for association with autism (SFARI); autism is frequently a phenotype of White-Sutton syndrome (see the human disease report 'autism spectrum disorder, susceptibility to' FBhh0000514).
Global RNAi-effected loss of function of Dmel\row results in lethality during the pupal stage. Pan-neuronal RNAi allows survival to adulthood; adults exhibit learning defects. Physical interactions of Dmel\row have been described; see below and in the gene report for row.
[updated Feb. 2021 by FlyBase; FBrf0222196
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996, pubmed:8655659; Risch et al., 1999, pubmed:10417292). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (MIM:608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008; pubmed:18698615). [from MIM:209850; 2017.03.18]
Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).
Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).
[WHITE-SUTTON SYNDROME; WHSUS](https://omim.org/entry/616364)
[POGO TRANSPOSABLE ELEMENT-DERIVED PROTEIN WITH ZNF DOMAIN; POGZ](https://omim.org/entry/614787)
White-Sutton syndrome is a neurodevelopmental disorder characterized by delayed psychomotor development apparent in infancy and a characteristic constellation of dysmorphic facial features. Additional features may include hypotonia, sensorineural hearing impairment, visual defects, joint laxity, and gastrointestinal difficulties, such as poor feeding (summary by White et al., 2016; pubmed:26739615). A significant number of patients have autism or autistic features (summary by Stessman et al., 2016; pubmed:26942287). [from MIM:616364; 2018.09.14]
The SFARI Gene autism database (https://gene.sfari.org) rates the gene-autism association for POGZ as high confidence (score 1).[2021.01.27]
White-Sutton syndrome (WHSUS) is caused by heterozygous mutation in the POGZ gene. [from MIM:616364; 2018.09.14]
POGZ encodes a zinc finger protein containing a transposase domain at the C-terminus; it appears to play a role in mitotic cell cycle progression and mitotic chromosome segregation. [Gene Cards, POGZ; 2017.03.20]
Many to one (4 human to 1 Drosophila); the human genes are POGZ, ZNF280C, ZNF280D, and ZNF280D.
Low- to moderate-scoring ortholog of human POGZ, ZNF280C, ZNF280D, and ZNF280D (1 Drosophila to 4 human). Dmel\row shares 23% identity and 35% similarity with human POGZ.
