Novel loss-of-function variants in TRIO are associated with neurodevelopmental disorder: case report.

Tytuł:: Novel loss-of-function variants in TRIO are associated with neurodevelopmental disorder: case report.
Autorzy:: Schultz-Rogers L; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
Muthusamy K; Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Pinto E Vairo F; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.; Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Klee EW; Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.; Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Lanpher B; Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA. .
Źródło:: BMC medical genetics [BMC Med Genet] 2020 Nov 10; Vol. 21 (1), pp. 219. Date of Electronic Publication: 2020 Nov 10.
Typ publikacji:: Case Reports; Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: London : BioMed Central, [2000-
MeSH Terms:: Autistic Disorder/*genetics
Developmental Disabilities/*genetics
Guanine Nucleotide Exchange Factors/*genetics
Megalencephaly/*genetics
Microcephaly/*genetics
Protein Serine-Threonine Kinases/*genetics
Adolescent ; Autistic Disorder/diagnosis ; Autistic Disorder/pathology ; Child, Preschool ; Developmental Disabilities/diagnosis ; Developmental Disabilities/pathology ; Female ; Frameshift Mutation ; Gene Expression ; Guanine Nucleotide Exchange Factors/deficiency ; Humans ; Inheritance Patterns ; Loss of Function Mutation ; Male ; Megalencephaly/diagnosis ; Megalencephaly/pathology ; Microcephaly/diagnosis ; Microcephaly/pathology ; Pedigree ; Protein Serine-Threonine Kinases/deficiency
References:: Am J Hum Genet. 2020 Mar 5;106(3):338-355. (PMID: 32109419)
Biochim Biophys Acta. 2007 Jun;1771(6):719-26. (PMID: 17428729)
Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2264-9. (PMID: 26858404)
Mol Psychiatry. 2019 Jul;24(7):1065-1078. (PMID: 29463886)
J Med Genet. 2016 Nov;53(11):735-742. (PMID: 27418539)
Exp Cell Res. 2013 Sep 10;319(15):2368-74. (PMID: 23769912)
Nat Commun. 2017 Sep 19;8(1):601. (PMID: 28928363)
Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5861-6. (PMID: 21422296)
Genet Med. 2019 Sep;21(9):2043-2058. (PMID: 30842647)
Cell Rep. 2019 Mar 5;26(10):2805-2817.e9. (PMID: 30840899)
Genes Dev. 2005 Jan 1;19(1):1-49. (PMID: 15630019)
Nature. 2014 Nov 13;515(7526):216-21. (PMID: 25363768)
Oncogene. 1998 Jan 15;16(2):147-52. (PMID: 9464532)
Biol Cell. 2006 Mar;98(3):183-93. (PMID: 16033331)
Nature. 2012 Apr 04;485(7397):237-41. (PMID: 22495306)
Nat Genet. 2017 Apr;49(4):504-510. (PMID: 28191890)
Hum Mutat. 2019 Sep;40(9):1330-1345. (PMID: 31144778)
Brain Res. 2015 May 22;1608:82-90. (PMID: 25727174)
Nat Neurosci. 2017 Aug;20(8):1043-1051. (PMID: 28628100)
J Genet Genomics. 2019 Feb;46(2):87-96. (PMID: 30850274)
Small GTPases. 2014;5:e29769. (PMID: 24987837)
Nature. 2002 Dec 12;420(6916):629-35. (PMID: 12478284)
J Biol Chem. 2004 Oct 15;279(42):43998-4004. (PMID: 15308664)
J Biol Chem. 2013 Feb 8;288(6):4486-500. (PMID: 23255595)
Hum Mol Genet. 2016 Mar 1;25(5):892-902. (PMID: 26721934)
Hum Mol Genet. 2017 Dec 1;26(23):4728-4740. (PMID: 28973398)
Nature. 2017 Feb 23;542(7642):433-438. (PMID: 28135719)
J Cell Sci. 2000 Feb;113 ( Pt 4):729-39. (PMID: 10652265)
Nat Commun. 2016 Nov 08;7:13316. (PMID: 27824329)
J Mol Biol. 2007 May 18;368(5):1307-20. (PMID: 17391702)
N Engl J Med. 2012 Nov 15;367(20):1921-9. (PMID: 23033978)
Clin Genet. 2019 Jan;95(1):151-159. (PMID: 30315573)
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12074-8. (PMID: 11050238)
Proc Natl Acad Sci U S A. 1996 May 28;93(11):5466-71. (PMID: 8643598)
Am J Hum Genet. 2018 Aug 2;103(2):171-187. (PMID: 30032986)
Gene. 2005 Feb 28;347(1):125-35. (PMID: 15715966)
Eur J Hum Genet. 2018 Jan;26(1):54-63. (PMID: 29209020)
Genet Med. 2018 Apr;20(4):435-443. (PMID: 28771251)
Mol Biol Cell. 2014 Dec 15;25(25):4063-71. (PMID: 25355950)
J Comp Neurol. 2005 Feb 21;482(4):333-48. (PMID: 15669055)
J Biol Chem. 2010 Aug 6;285(32):24834-44. (PMID: 20516067)
Contributed Indexing:: Keywords: Autism; Cutis aplasia; Macrocephaly; Microcephaly; TRIO gene
Substance Nomenclature:: 0 (Guanine Nucleotide Exchange Factors)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.11.1 (TRIO protein, human)
Entry Date(s):: Date Created: 20201110 Date Completed: 20210108 Latest Revision: 20211204
Update Code:: 20240105
PubMed Central ID:: PMC7654171
DOI:: 10.1186/s12881-020-01159-y
PMID:: 33167890
: Czasopismo naukowe

Pełny tekst

Background: Damaging variants in TRIO have been associated with moderate to severe neurodevelopmental disorders in humans. While recent work has delineated the positional effect of missense variation on the resulting phenotype, the clinical spectrum associated with loss-of-function variation has yet to be fully defined.
Case Presentation: We report on two probands with novel loss-of-function variants in TRIO. Patient 1 presents with a severe neurodevelopmental disorder and macrocephaly. The TRIO variant is inherited from his affected mother. Patient 2 presents with moderate developmental delays, microcephaly, and cutis aplasia with a frameshift variant of unknown inheritance.
Conclusions: We describe two patients with neurodevelopmental disorder, macro/microcephaly, and cutis aplasia in one patient. Both patients have loss-of-function variants, helping to further characterize how these types of variants affect the phenotypic spectrum associated with TRIO. We also present the third reported case of autosomal dominant inheritance of a damaging variant in TRIO.

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