Homozygous Null TBX4 Mutations Lead to Posterior Amelia with Pelvic and Pulmonary Hypoplasia.
Abnormalities, Multiple
/ etiology
Adolescent
Bone Diseases, Developmental
/ etiology
Child
Ectromelia
/ etiology
Female
Hip
/ abnormalities
Homozygote
Humans
Ischium
/ abnormalities
Loss of Function Mutation
Lung
/ abnormalities
Lung Diseases
/ etiology
Male
Patella
/ abnormalities
Pedigree
Pelvis
/ abnormalities
Prognosis
T-Box Domain Proteins
/ genetics
PAPPAS
SPS
TBX4
Xenopus
allelic diseases
animal models
hindlimb amelia
lung and pelvis hypoplasia
semi-dominant
small patella syndrome
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
05 12 2019
05 12 2019
Historique:
received:
18
07
2019
accepted:
25
10
2019
pubmed:
26
11
2019
medline:
3
4
2020
entrez:
26
11
2019
Statut:
ppublish
Résumé
The development of hindlimbs in tetrapod species relies specifically on the transcription factor TBX4. In humans, heterozygous loss-of-function TBX4 mutations cause dominant small patella syndrome (SPS) due to haploinsufficiency. Here, we characterize a striking clinical entity in four fetuses with complete posterior amelia with pelvis and pulmonary hypoplasia (PAPPA). Through exome sequencing, we find that PAPPA syndrome is caused by homozygous TBX4 inactivating mutations during embryogenesis in humans. In two consanguineous couples, we uncover distinct germline TBX4 coding mutations, p.Tyr113
Identifiants
pubmed: 31761294
pii: S0002-9297(19)30401-X
doi: 10.1016/j.ajhg.2019.10.013
pmc: PMC6904794
pii:
doi:
Substances chimiques
T-Box Domain Proteins
0
TBX4 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1294-1301Informations de copyright
Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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