LINKED syndrome OTUD5 X-linked intellectual disability congenital malformation deubiquitinase

Journal

Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250

Informations de publication

Date de publication:
2021
Historique:
received: 23 11 2020
accepted: 25 01 2021
entrez: 22 3 2021
pubmed: 23 3 2021
medline: 23 3 2021
Statut: epublish

Résumé

X-linked intellectual disability (XLID), which occurs predominantly in males, is a relatively common and genetically heterogeneous disorder in which over 100 mutated genes have been reported. The We investigated three affected males (49- and 47-year-old brothers [Individuals 1 and 2] and a 2-year-old boy [Individual 3]) from two families who showed developmental delay. Their common clinical features included developmental delay, hypotonia, short stature, and distinctive facial features, such as telecanthus and a depressed nasal bridge. Individuals 1 and 2 showed epilepsy and brain magnetic resonance imaging showed a thin corpus callosum and mild ventriculomegaly. Individual 3 showed congenital malformations, including tetralogy of Fallot, hypospadias, and bilateral cryptorchidism. To identify the genetic cause of these features, we performed whole-exome sequencing. A hemizygous Unlike previous reports of LINKED syndrome, which described early lethality with congenital cardiac anomalies, our three cases are still alive. Notably, the adult brothers with the novel missense

Sections du résumé

BACKGROUND BACKGROUND
X-linked intellectual disability (XLID), which occurs predominantly in males, is a relatively common and genetically heterogeneous disorder in which over 100 mutated genes have been reported. The
METHODS METHODS
We investigated three affected males (49- and 47-year-old brothers [Individuals 1 and 2] and a 2-year-old boy [Individual 3]) from two families who showed developmental delay. Their common clinical features included developmental delay, hypotonia, short stature, and distinctive facial features, such as telecanthus and a depressed nasal bridge. Individuals 1 and 2 showed epilepsy and brain magnetic resonance imaging showed a thin corpus callosum and mild ventriculomegaly. Individual 3 showed congenital malformations, including tetralogy of Fallot, hypospadias, and bilateral cryptorchidism. To identify the genetic cause of these features, we performed whole-exome sequencing.
RESULTS RESULTS
A hemizygous
CONCLUSIONS CONCLUSIONS
Unlike previous reports of LINKED syndrome, which described early lethality with congenital cardiac anomalies, our three cases are still alive. Notably, the adult brothers with the novel missense

Identifiants

pubmed: 33748114
doi: 10.3389/fcell.2021.631428
pmc: PMC7965969
doi:

Types de publication

Journal Article

Langues

eng

Pagination

631428

Informations de copyright

Copyright © 2021 Saida, Fukuda, Scott, Sengoku, Ogata, Nicosia, Hernandez-Garcia, Lalani, Azamian, Streff, Liu, Dai, Mizuguchi, Miyatake, Asahina, Ogata, Miyake and Matsumoto.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

Clin Genet. 2021 Feb;99(2):303-308
pubmed: 33131077
Am J Hum Genet. 2020 Jan 2;106(1):13-25
pubmed: 31839203
J Pediatr Endocrinol Metab. 1998 Mar-Apr;11(2):261-5
pubmed: 9642641
Am J Hum Genet. 2017 Feb 2;100(2):267-280
pubmed: 28132688
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Sci Adv. 2021 Jan 20;7(4):
pubmed: 33523931
Am J Med Genet A. 2018 Jun;176(6):1375-1388
pubmed: 29696803
Hum Mutat. 2015 Oct;36(10):928-30
pubmed: 26220891
JAMA. 2014 Nov 12;312(18):1870-9
pubmed: 25326635
Nat Rev Mol Cell Biol. 2012 Jul 23;13(8):508-23
pubmed: 22820888
Eur J Hum Genet. 2015 Nov;23(11):1513-8
pubmed: 25649377
Am J Hum Genet. 2012 Apr 6;90(4):579-90
pubmed: 22482801
Nat Rev Mol Cell Biol. 2009 Aug;10(8):550-63
pubmed: 19626045
Cell Death Differ. 2021 Feb;28(2):538-556
pubmed: 33335288
Nat Struct Mol Biol. 2012 Jan 15;19(2):171-5
pubmed: 22245969
Am J Med Genet A. 2011 Aug;155A(8):1906-16
pubmed: 21744490
Cell. 2013 Jul 3;154(1):169-84
pubmed: 23827681
Eur J Hum Genet. 2014 Jan;22(1):79-87
pubmed: 23695279
OMICS. 2017 May;21(5):295-303
pubmed: 28481730
N Engl J Med. 2013 Oct 17;369(16):1502-11
pubmed: 24088041

Auteurs

Ken Saida (K)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Tokiko Fukuda (T)

Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Daryl A Scott (DA)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.
Texas Children's Hospital, Houston, TX, United States.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, United States.

Toru Sengoku (T)

Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Kazuhiro Ogata (K)

Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Annarita Nicosia (A)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, United States.

Andres Hernandez-Garcia (A)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.

Seema R Lalani (SR)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.
Texas Children's Hospital, Houston, TX, United States.

Mahshid S Azamian (MS)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.

Haley Streff (H)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.
Texas Children's Hospital, Houston, TX, United States.

Pengfei Liu (P)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.
Baylor Genetics, Houston, TX, United States.

Hongzheng Dai (H)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.
Baylor Genetics, Houston, TX, United States.

Takeshi Mizuguchi (T)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Satoko Miyatake (S)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Miki Asahina (M)

Department of Pediatrics, Hamamatsu City Welfare and Medical Center for Development, Hamamatsu, Japan.

Tsutomu Ogata (T)

Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Noriko Miyake (N)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Naomichi Matsumoto (N)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Classifications MeSH