PURPOSE: The purpose of this study was to expand the genetic architecture of neurodevelopmental disorders, and to characterize the clinical features of a novel cohort of affected individuals with variants in ZNF142, a C2H2 domain-containing transcription factor. METHODS: Four independent research centers used exome sequencing to elucidate the genetic basis of neurodevelopmental phenotypes in four unrelated families. Following bioinformatic filtering, query of control data sets, and secondary variant confirmation, we aggregated findings using an online data sharing platform. We performed in-depth clinical phenotyping in all affected individuals. RESULTS: We identified seven affected females in four pedigrees with likely pathogenic variants in ZNF142 that segregate with recessive disease. Affected cases in three families harbor either nonsense or frameshifting likely pathogenic variants predicted to undergo nonsense mediated decay. One additional trio bears ultrarare missense variants in conserved regions of ZNF142 that are predicted to be damaging to protein function. We performed clinical comparisons across our cohort and noted consistent presence of intellectual disability and speech impairment, with variable manifestation of seizures, tremor, and dystonia. CONCLUSION: Our aggregate data support a role for ZNF142 in nervous system development and add to the emergent list of zinc finger proteins that contribute to neurocognitive disorders.

• Klíčová slova
• ataxia, childhood apraxia of speech, developmental delay, dolichocephaly, homozygosity mapping,
• MeSH
• dítě MeSH
• dospělí MeSH
• dystonie genetika   MeSH
• fenotyp MeSH
• kohortové studie MeSH
• lidé MeSH
• mentální retardace genetika   MeSH
• missense mutace MeSH
• mladiství MeSH
• mutace MeSH
• neurovývojové poruchy genetika   MeSH
• poruchy řeči genetika   MeSH
• rodina MeSH
• rodokmen MeSH
• sekvenování exomu MeSH
• trans-aktivátory genetika   metabolismus   MeSH
• výpočetní biologie metody   MeSH
• vývojové poruchy u dětí genetika   MeSH
• záchvaty genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• trans-aktivátory MeSH
• ZNF143 protein, human MeSH Prohlížeč