Recurrent homozygous damaging mutation in
Amino Acid Sequence
/ genetics
Child
Child, Preschool
Consanguinity
Endoplasmic Reticulum
/ genetics
Exons
/ genetics
Female
Genetic Predisposition to Disease
Homozygote
Humans
Male
Membrane Proteins
/ genetics
Microcephaly
/ genetics
Mutation
/ genetics
Protein Disulfide-Isomerases
/ genetics
Protein Folding
Thioredoxins
/ genetics
Exome Sequencing
ER stress
TMX2
microlissencephaly
protein disulfide isomerase
thioredoxin
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
28
06
2019
revised:
26
08
2019
accepted:
06
09
2019
pubmed:
7
10
2019
medline:
5
2
2021
entrez:
7
10
2019
Statut:
ppublish
Résumé
Protein disulfide isomerase (PDI) proteins are part of the thioredoxin protein superfamily. PDIs are involved in the formation and rearrangement of disulfide bonds between cysteine residues during protein folding in the endoplasmic reticulum and are implicated in stress response pathways. Eight children from four consanguineous families residing in distinct geographies within the Middle East and Central Asia were recruited for study. All probands showed structurally similar microcephaly with lissencephaly (microlissencephaly) brain malformations. DNA samples from each family underwent whole exome sequencing, assessment for repeat expansions and confirmatory segregation analysis. An identical homozygous variant in The
Sections du résumé
BACKGROUND
Protein disulfide isomerase (PDI) proteins are part of the thioredoxin protein superfamily. PDIs are involved in the formation and rearrangement of disulfide bonds between cysteine residues during protein folding in the endoplasmic reticulum and are implicated in stress response pathways.
METHODS
Eight children from four consanguineous families residing in distinct geographies within the Middle East and Central Asia were recruited for study. All probands showed structurally similar microcephaly with lissencephaly (microlissencephaly) brain malformations. DNA samples from each family underwent whole exome sequencing, assessment for repeat expansions and confirmatory segregation analysis.
RESULTS
An identical homozygous variant in
CONCLUSION
The
Identifiants
pubmed: 31586943
pii: jmedgenet-2019-106409
doi: 10.1136/jmedgenet-2019-106409
pmc: PMC7405652
mid: NIHMS1597846
doi:
Substances chimiques
Membrane Proteins
0
TMX2 protein, human
0
Thioredoxins
52500-60-4
Protein Disulfide-Isomerases
EC 5.3.4.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
274-282Subventions
Organisme : NHGRI NIH HHS
ID : UM1 HG008900
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG003067
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS047101
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIH HHS
ID : S10 OD018521
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS048453
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG006504
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 AG000949
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS052455
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008666
Pays : United States
Organisme : NICHD NIH HHS
ID : F31 HD095602
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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