Genetic testing of nonsyndromic cases (at least for FGFR3P250R and FGFR2 exons IIIa/c) should be targeted to patients with coronal or multisuture synostoses.
Genetic testing of nonsyndromic cases (at least for FGFR3 P250R and FGFR2 exons IIIa/c) should be targeted to patients with coronal or multisuture synostoses.
Resequencing of the coding regions, splice junction sites, and 5' and 3' untranslated regions of 27 candidate genes in 186 cases of isolated non-syndromic single suture synostosis revealed three novel and two rare sequence variants (R406H, R595H, N857S, P190S, M446V) in insulin-like growth factor I receptor (IGF1R) that are enriched relative to control samples.
In particular, coronal synostosis evidences a higher tendency to be genetically caused, and TWIST1 and FGFR3 have been identified as major causative genes.
We show that TCF12 and TWIST1 act synergistically in a transactivation assay and that mice doubly heterozygous for loss-of-function mutations in Tcf12 and Twist1 have severe coronal synostosis.
We show that TCF12 and TWIST1 act synergistically in a transactivation assay and that mice doubly heterozygous for loss-of-function mutations in Tcf12 and Twist1 have severe coronal synostosis.
TCF12 molecular testing should be considered in patients with unilateral- or bilateral-coronal synostosis associated or not with syndactyly, after having excluded mutations in the TWIST1 gene and the p.Pro250Arg mutation in FGFR3.
The diagnosis of a ZIC1 mutation has significant implications for prognosis and we recommend genetic testing when common causes of coronal synostosis have been excluded.
Using genetic data obtained from a six-generation Chinese family, we identified a missense variant in GDF6 (NP_001001557.1; p.Y444N) that fully segregates with a novel autosomal dominant synostoses (SYNS) phenotype, which we designate as SYNS4.
This woman homozygous for c.1303G>A; p.(Gly435Ser) in CYP26B1, which was associated with multisutural synostosis, radiohumeral synostosis, normal bone mineral density, and apparent intellectual disability, a phenotype with significant similarities to Antley-Bixler and Pfeiffer syndromes.
We have demonstrated for the first time that mutations in FGF9 cause craniosynostosis in humans and confirm that FGF9 mutations cause multiple synostoses.
We hypothesize that, identical to the recently published GDF6-related multiple synostoses family, the p.Ser429Arg mutation also leads to a gain of function.
We examined longitudinal serum and urine steroid metabolite profiles in a 46,XY infant with PORD who was prenatally identified because of the progressive fetal masculinization and maternal virilization from the mid-gestation and the presence of fetal radio-humeral synostosis and was confirmed to have compound heterozygous mutations of POR (p.Q201X and p.R457H).
Here, we identified a de novo missense mutation, p.Arg235Gln in the highly conserved TALE homeodomain of the transcription factor Pre-B-Cell Leukemia Transcription Factor 1 (PBX1) in a child with 46,XY gonadal dysgenesis and radiocubital synostosis.
Compound heterozygous mice with selective disinhibition of RUNX2 and either overexpression of IGF1 or loss of function of GSK3β demonstrated an increase in the frequency and severity of synostosis as compared to mice with the RUNX2 disinhibition alone.
Compound heterozygous mice with selective disinhibition of RUNX2 and either overexpression of IGF1 or loss of function of GSK3β demonstrated an increase in the frequency and severity of synostosis as compared to mice with the RUNX2 disinhibition alone.