2020
DOI: 10.1002/humu.24071
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Biallelic loss‐of‐function variants in TBC1D2B cause a neurodevelopmental disorder with seizures and gingival overgrowth

Abstract: The family of Tre2‐Bub2‐Cdc16 (TBC)‐domain containing GTPase activating proteins (RABGAPs) is not only known as key regulatorof RAB GTPase activity but also has GAP‐independent functions. Rab GTPases are implicated in membrane trafficking pathways, such as vesicular trafficking. We report biallelic loss‐of‐function variants in TBC1D2B, encoding a member of the TBC/RABGAP family with yet unknown function, as the underlying cause of cognitive impairment, seizures, and/or gingival overgrowth in three individuals … Show more

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Cited by 11 publications
(31 citation statements)
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“…Eight genes were selected for further analysis and had been used as prognostic markers in other diseases. CDC16 has a connection with multiple neurodevelopmental disorders ( 50 , 51 ). It has been found that CDC16 has potential therapeutic function in melanoma ( 52 ).…”
Section: Discussionmentioning
confidence: 99%
“…Eight genes were selected for further analysis and had been used as prognostic markers in other diseases. CDC16 has a connection with multiple neurodevelopmental disorders ( 50 , 51 ). It has been found that CDC16 has potential therapeutic function in melanoma ( 52 ).…”
Section: Discussionmentioning
confidence: 99%
“…RNA isolation, complementary DNA (cDNA) synthesis, and quantitative reverse transcription PCR (RT-qPCR) to determine the relative HS2ST1 mRNA amount in fibroblasts of affected and healthy individuals were performed as previously described. 23 Qualitative RT-PCR to analyze HS2ST1 transcripts was performed on fibroblast-derived cDNA according to standard PCR protocols with the OneTaq Quick-Load 2X Master Mix (New England Biolabs). PCR products were directly Sanger-sequenced.…”
Section: Transcript Analysismentioning
confidence: 99%
“…Cell lysates from affected individuals' and control fibroblasts were prepared, and immunoblotting was performed as previously described. 23 Briefly, cells were harvested in ice-cold RIPA buffer and protein extracts were separated on SDS-PAGE and transferred to polyvinylidene fluoride membranes. The membrane was incubated with the indicated primary antibody at 4 C overnight and fluorescent dye-linked secondary antibodies at room temperature for 1 h.…”
Section: Immunoblot Analysismentioning
confidence: 99%
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“…TBC1D2 has in vitro GAP activity toward Rab7 and regulates endosome trafficking and autophagy (Frasa et al ., 2010; Serva et al ., 2012; Carroll et al ., 2013; Toyofuku et al ., 2015; Jaber et al ., 2016). TBC1D2B interacts with Rab22 and Rab31, Rab5 related GTPases, and colocalizes with Rab5 and Rab7, but a specific Rab GTPase target of GAP activity has not been demonstrated (Kanno et al ., 2010; Manshouri et al ., 2019; Harms et al ., 2020; Wei et al ., 2021).…”
Section: Introductionmentioning
confidence: 99%