Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, germline variants of the transcriptional co-regulator gene TCF20 have been implicated in the aetiology of autism spectrum disorders (ASD). However, the knowledge about the associated clinical picture remains fragmentary. In this study, two individuals with de novo TCF20 sequence variants were identified in a cohort of 313 individuals with intellectual disability of unknown aetiology, which was analysed by whole exome sequencing using a child-parent trio design. Both detected variants - one nonsense and one frameshift variant - were truncating. A comprehensive clinical characterisation of the patients yielded mild intellectual disability, postnatal tall stature and macrocephaly, obesity and muscular hypotonia as common clinical signs while ASD was only present in one proband. The present report begins to establish the clinical picture of individuals with de novo nonsense and frameshift variants of TCF20 which includes features such as proportionate overgrowth and muscular hypotonia. Furthermore, intellectual disability/developmental delay seems to be fully penetrant amongst known individuals with de novo nonsense and frameshift variants of TCF20, whereas ASD is shown to be incompletely penetrant. The transcriptional co-regulator gene TCF20 is hereby added to the growing number of genes implicated in the aetiology of both ASD and intellectual disability. Furthermore, such de novo variants of TCF20 may represent a novel differential diagnosis in the overgrowth syndrome spectrum.
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PMID:De novo nonsense and frameshift variants of TCF20 in individuals with intellectual disability and postnatal overgrowth. 2743 65

Phelan-McDermid syndrome (PMS, OMIM 606232) is a heterozygous contiguous gene microdeletion syndrome occurring at the distal region of chromosome 22q13. This deletion encompasses the SHANK3 gene at 22q13.33, which is thought to be the critical gene for the neurodevelopmental features seen in this syndrome. PMS is typically characterized by intellectual disability, autism spectrum disorder, absent to severely delayed speech, neonatal hypotonia, and dysmorphic features. Two patients presenting with classic clinical features of PMS have been reported to have interstitial microdeletions in the 22q13.2 region that map proximal to the SHANK3 gene (0.54 and 0.72 Mb, respectively). Here, we describe a 13-month-old girl with a de novo 1.16 Mb interstitial deletion in the 22q13.2 region who presented with global developmental delay, subtle dysmorphic features, and immunodeficiency. This deletion overlaps with the two previously published cases and five cases from the DECIPHER database. All eight patients share features common to patients with PMS including developmental delay and language delay, which suggests that this represents a previously unrecognized microdeletion syndrome in the 22q13.2 region. Our patient's deletion encompasses the TCF20 and TNFRSF13C genes, which are thought to play causative roles in the patient's neurodevelopmental and immunological features, respectively.
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PMID:A previously unrecognized 22q13.2 microdeletion syndrome that encompasses TCF20 and TNFRSF13C. 3021 95