%0 Journal Article %J Genome Med %D 2019 %T Correction to: De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome. %A Vetrini, Francesco %A McKee, Shane %A Rosenfeld, Jill A %A Suri, Mohnish %A Lewis, Andrea M %A Nugent, Kimberly Margaret %A Roeder, Elizabeth %A Littlejohn, Rebecca O %A Holder, Sue %A Zhu, Wenmiao %A Alaimo, Joseph T %A Graham, Brett %A Harris, Jill M %A Gibson, James B %A Pastore, Matthew %A McBride, Kim L %A Komara, Makanko %A Al-Gazali, Lihadh %A Al Shamsi, Aisha %A Fanning, Elizabeth A %A Wierenga, Klaas J %A Scott, Daryl A %A Ben-Neriah, Ziva %A Meiner, Vardiella %A Cassuto, Hanoch %A Elpeleg, Orly %A Lloyd Holder, J %A Burrage, Lindsay C %A Seaver, Laurie H %A Van Maldergem, Lionel %A Mahida, Sonal %A Soul, Janet S %A Marlatt, Margaret %A Matyakhina, Ludmila %A Vogt, Julie %A Gold, June-Anne %A Park, Soo-Mi %A Varghese, Vinod %A Lampe, Anne K %A Kumar, Ajith %A Lees, Melissa %A Holder-Espinasse, Muriel %A McConnell, Vivienne %A Bernhard, Birgitta %A Blair, Ed %A Harrison, Victoria %A Donna M Muzny %A Richard A Gibbs %A Sarah H Elsea %A Posey, Jennifer E %A Bi, Weimin %A Lalani, Seema %A Xia, Fan %A Yang, Yaping %A Eng, Christine M %A James R Lupski %A Liu, Pengfei %X

It was highlighted that the original article [1] contained a typographical error in the Results section. Subject 17 was incorrectly cited as Subject 1. This Correction article shows the revised statement. The original article has been updated.

%B Genome Med %V 11 %P 16 %8 2019 Mar 25 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/30909959?dopt=Abstract %R 10.1186/s13073-019-0630-1 %0 Journal Article %J Genome Med %D 2019 %T De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith-Magenis syndrome. %A Vetrini, Francesco %A McKee, Shane %A Rosenfeld, Jill A %A Suri, Mohnish %A Lewis, Andrea M %A Nugent, Kimberly Margaret %A Roeder, Elizabeth %A Littlejohn, Rebecca O %A Holder, Sue %A Zhu, Wenmiao %A Alaimo, Joseph T %A Graham, Brett %A Harris, Jill M %A Gibson, James B %A Pastore, Matthew %A McBride, Kim L %A Komara, Makanko %A Al-Gazali, Lihadh %A Al Shamsi, Aisha %A Fanning, Elizabeth A %A Wierenga, Klaas J %A Scott, Daryl A %A Ben-Neriah, Ziva %A Meiner, Vardiella %A Cassuto, Hanoch %A Elpeleg, Orly %A Holder, J Lloyd %A Burrage, Lindsay C %A Seaver, Laurie H %A Van Maldergem, Lionel %A Mahida, Sonal %A Soul, Janet S %A Marlatt, Margaret %A Matyakhina, Ludmila %A Vogt, Julie %A Gold, June-Anne %A Park, Soo-Mi %A Varghese, Vinod %A Lampe, Anne K %A Kumar, Ajith %A Lees, Melissa %A Holder-Espinasse, Muriel %A McConnell, Vivienne %A Bernhard, Birgitta %A Blair, Ed %A Harrison, Victoria %A Donna M Muzny %A Richard A Gibbs %A Sarah H Elsea %A Posey, Jennifer E %A Bi, Weimin %A Lalani, Seema %A Xia, Fan %A Yang, Yaping %A Eng, Christine M %A James R Lupski %A Liu, Pengfei %K Adolescent %K Child %K Child, Preschool %K Craniofacial Abnormalities %K Developmental Disabilities %K Female %K Humans %K INDEL Mutation %K Infant %K Intellectual Disability %K Male %K Muscle Hypotonia %K Smith-Magenis Syndrome %K Transcription Factors %K Young Adult %X

BACKGROUND: Neurodevelopmental disorders are genetically and phenotypically heterogeneous encompassing developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), structural brain abnormalities, and neurological manifestations with variants in a large number of genes (hundreds) associated. To date, a few de novo mutations potentially disrupting TCF20 function in patients with ID, ASD, and hypotonia have been reported. TCF20 encodes a transcriptional co-regulator structurally related to RAI1, the dosage-sensitive gene responsible for Smith-Magenis syndrome (deletion/haploinsufficiency) and Potocki-Lupski syndrome (duplication/triplosensitivity).

METHODS: Genome-wide analyses by exome sequencing (ES) and chromosomal microarray analysis (CMA) identified individuals with heterozygous, likely damaging, loss-of-function alleles in TCF20. We implemented further molecular and clinical analyses to determine the inheritance of the pathogenic variant alleles and studied the spectrum of phenotypes.

RESULTS: We report 25 unique inactivating single nucleotide variants/indels (1 missense, 1 canonical splice-site variant, 18 frameshift, and 5 nonsense) and 4 deletions of TCF20. The pathogenic variants were detected in 32 patients and 4 affected parents from 31 unrelated families. Among cases with available parental samples, the variants were de novo in 20 instances and inherited from 4 symptomatic parents in 5, including in one set of monozygotic twins. Two pathogenic loss-of-function variants were recurrent in unrelated families. Patients presented with a phenotype characterized by developmental delay, intellectual disability, hypotonia, variable dysmorphic features, movement disorders, and sleep disturbances.

CONCLUSIONS: TCF20 pathogenic variants are associated with a novel syndrome manifesting clinical characteristics similar to those observed in Smith-Magenis syndrome. Together with previously described cases, the clinical entity of TCF20-associated neurodevelopmental disorders (TAND) emerges from a genotype-driven perspective.

%B Genome Med %V 11 %P 12 %8 2019 Feb 28 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/30819258?dopt=Abstract %R 10.1186/s13073-019-0623-0