Exome survey of individuals affected by VATER/VACTERL with renal phenotypes identifies phenocopies and novel candidate genes.
Anorectal Malformations
/ complications
Cytoskeletal Proteins
/ genetics
DNA-Binding Proteins
/ genetics
Esophageal Atresia
/ complications
Female
Genes, X-Linked
/ genetics
Genetic Association Studies
Genetic Predisposition to Disease
HSP90 Heat-Shock Proteins
/ genetics
Heart Diseases
/ complications
Hemizygote
Homeodomain Proteins
/ genetics
Humans
Kidney
/ abnormalities
Male
Receptors, Interleukin
/ genetics
Tracheoesophageal Fistula
/ complications
Transcription Factors
/ genetics
Exome Sequencing
VATER/VACTERL association
anorectal malformation (ARM)
congenital anomalies of the kidneys and urinary tract (CAKUT)
exome sequencing (WES)
monogenic disease causation
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
13
07
2021
received:
05
02
2021
accepted:
17
07
2021
pubmed:
3
8
2021
medline:
3
3
2022
entrez:
2
8
2021
Statut:
ppublish
Résumé
The acronym VATER/VACTERL refers to the rare nonrandom association of the following component features (CFs): vertebral defects (V), anorectal malformations (ARM) (A), cardiac anomalies (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb anomalies (L). For the clinical diagnosis, the presence of at least three CFs is required, individuals presenting with only two CFs have been categorized as VATER/VACTERL-like. The majority of VATER/VACTERL individuals displays a renal phenotype. Hitherto, variants in FGF8, FOXF1, HOXD13, LPP, TRAP1, PTEN, and ZIC3 have been associated with the VATER/VACTERL association; however, large-scale re-sequencing could only confirm TRAP1 and ZIC3 as VATER/VACTERL disease genes, both associated with a renal phenotype. In this study, we performed exome sequencing in 21 individuals and their families with a renal VATER/VACTERL or VATER/VACTERL-like phenotype to identify potentially novel genetic causes. Exome analysis identified biallelic and X-chromosomal hemizygous potentially pathogenic variants in six individuals (29%) in B9D1, FREM1, ZNF157, SP8, ACOT9, and TTLL11, respectively. The online tool GeneMatcher revealed another individual with a variant in ZNF157. Our study suggests six biallelic and X-chromosomal hemizygous VATER/VACTERL disease genes implicating all six genes in the expression of human renal malformations.
Identifiants
pubmed: 34338422
doi: 10.1002/ajmg.a.62447
pmc: PMC8595524
mid: NIHMS1726921
doi:
Substances chimiques
B9D1 protein, human
0
Cytoskeletal Proteins
0
DNA-Binding Proteins
0
Frem1 protein, human
0
HSP90 Heat-Shock Proteins
0
Homeodomain Proteins
0
Receptors, Interleukin
0
Sp8 protein, human
0
TRAP1 protein, human
0
Transcription Factors
0
ZIC3 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3784-3792Subventions
Organisme : NHGRI NIH HHS
ID : UM1 HG008900
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK088767
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079310
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK076683
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG006504
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK068306
Pays : United States
Organisme : CIHR
Pays : Canada
Organisme : NIDDK NIH HHS
ID : T32 DK007726
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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