Dental abnormalities in Schimke immuno-osseous dysplasia.
Described for the first time in 1971, Schimke immuno-osseous dysplasia (SIOD) is an autosomal-recessive multisystem disorder that is caused by bi-allelic mutations of SMARCAL1, which encodes a DNA annealing helicase. To define better the dental anomalies of SIOD, we reviewed the records from SIOD patients with identified bi-allelic SMARCAL1 mutations, and we found that 66.0% had microdontia, hypodontia, or malformed deciduous and permanent molars. Immunohistochemical analyses showed expression of SMARCAL1 in all developing teeth, raising the possibility that the malformations are cell-autonomous consequences of SMARCAL1 deficiency. We also found that stimulation of cultured skin fibroblasts from SIOD patients with the tooth morphogens WNT3A, BMP4, and TGFβ1 identified altered transcriptional responses, raising the hypothesis that the dental malformations arise in part from altered responses to developmental morphogens. To the best of our knowledge, this is the first systematic study of the dental anomalies associated with SIOD.
Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
M
M
Morimoto
O
O
Kérourédan
M
M
Gendronneau
C
C
Shuen
A
A
Baradaran-Heravi
Y
Y
Asakura
M
M
Basiratnia
R
R
Bogdanovic
D
D
Bonneau
A
A
Buck
J
J
Charrow
P
P
Cochat
K A
KA
Dehaai
M S
MS
Fenkçi
P
P
Frange
S
S
Fründ
H
H
Fryssira
K
K
Keller
S
S
Kirmani
C
C
Kobelka
K
K
Kohler
D B
DB
Lewis
L
L
Massella
D R
DR
McLeod
D V
DV
Milford
F
F
Nobili
A H
AH
Olney
C N
CN
Semerci
N
N
Stajic
A
A
Stein
S
S
Taque
J
J
Zonana
T
T
Lücke
G
G
Hendson
M
M
Bonnaure-Mallet
C F
CF
Boerkoel
D000483:Alleles; D000848:Anodontia / Q000209:etiology; D001161:Arteriosclerosis / Q000150:complications* / Q000235:genetics; D001641:Bicuspid / Q000002:abnormalities; D055415:Bone Morphogenetic Protein 4 / Q000032:analysis; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004265:DNA Helicases / Q000032:analysis / Q000235:genetics; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000235:genetics; D008963:Molar / Q000002:abnormalities; D009154:Mutation / Q000235:genetics; D009404:Nephrotic Syndrome / Q000150:complications* / Q000235:genetics; D009805:Odontogenesis / Q000235:genetics; D010009:Osteochondrodysplasias / Q000150:complications* / Q000235:genetics; D000081207:Primary Immunodeficiency Diseases; D011655:Pulmonary Embolism / Q000150:complications* / Q000235:genetics; D012867:Skin / Q000166:cytology; D014071:Tooth Abnormalities / Q000209:etiology*; D014083:Tooth Germ / Q000473:pathology; D014092:Tooth Root / Q000002:abnormalities; D014094:Tooth, Deciduous / Q000002:abnormalities; D014158:Transcription, Genetic / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D060509:Wnt3A Protein / Q000032:analysis
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D053773:Transforming Growth Factor beta1; C555510:WNT3A protein, human; D060509:Wnt3A Protein; C412482:SMARCAL1 protein, human; D004265:DNA Helicases