TY  - JOUR
A1  - Dubail, Johanne
A1  - Huber, Céline
A1  - Chantepie, Sandrine
A1  - Sonntag, Stephan
A1  - Tüysüz, Beyhan
A1  - Mihci, Ercan
A1  - Gordon, Christopher T.
A1  - Steichen-Gersdorf, Elisabeth
A1  - Amiel, Jeanne
A1  - Nur, Banu
A1  - Stolte-Dijkstra, Irene
A1  - van Eerde, Albertien M.
A1  - van Gassen, Koen L.
A1  - Breugem, Corstiaan C.
A1  - Stegmann, Alexander
A1  - Lekszas, Caroline
A1  - Maroofian, Reza
A1  - Karimiani, Ehsan Ghayoor
A1  - Bruneel, Arnaud
A1  - Seta, Nathalie
A1  - Munnich, Arnold
A1  - Papy-Garcia, Dulce
A1  - De La Dure-Molla, Muriel
A1  - Cormier-Daire, Valérie
T1  - SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects
JF  - Nature Communications
N2  - Skeletal dysplasia with multiple dislocations are severe disorders characterized by dislocations of large joints and short stature. The majority of them have been linked to pathogenic variants in genes encoding glycosyltransferases, sulfotransferases or epimerases required for glycosaminoglycan synthesis. Using exome sequencing, we identify homozygous mutations in SLC10A7 in six individuals with skeletal dysplasia with multiple dislocations and amelogenesis imperfecta. SLC10A7 encodes a 10-transmembrane-domain transporter located at the plasma membrane. Functional studies in vitro demonstrate that SLC10A7 mutations reduce SLC10A7 protein expression. We generate a Slc10a7−/− mouse model, which displays shortened long bones, growth plate disorganization and tooth enamel anomalies, recapitulating the human phenotype. Furthermore, we identify decreased heparan sulfate levels in Slc10a7−/− mouse cartilage and patient fibroblasts. Finally, we find an abnormal N-glycoprotein electrophoretic profile in patient blood samples. Together, our findings support the involvement of SLC10A7 in glycosaminoglycan synthesis and specifically in skeletal development.
KW  - bone development
KW  - disease genetics
KW  - medical genetics
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226377
VL  - 9
ER  - 
TY  - JOUR
A1  - Lekszas, Caroline
A1  - Nanda, Indrajit
A1  - Vona, Barbara
A1  - Böck, Julia
A1  - Ashrafzadeh, Farah
A1  - Donyadideh, Nahid
A1  - Ebrahimzadeh, Farnoosh
A1  - Ahangari, Najmeh
A1  - Maroofian, Reza
A1  - Karimiani, Ehsan Ghayoor
A1  - Haaf, Thomas
T1  - Unbalanced segregation of a paternal t(9;11)(p24.3;p15.4) translocation causing familial Beckwith-Wiedemann syndrome: a case report
JF  - BMC Medical Genomics
N2  - Background
The vast majority of cases with Beckwith-Wiedemann syndrome (BWS) are caused by a molecular defect in the imprinted chromosome region 11p15.5. The underlying mechanisms include epimutations, uniparental disomy, copy number variations, and structural rearrangements. In addition, maternal loss-of-function mutations in CDKN1C are found. Despite growing knowledge on BWS pathogenesis, up to 20% of patients with BWS phenotype remain without molecular diagnosis.

Case presentation
Herein, we report an Iranian family with two females affected with BWS in different generations. Bisulfite pyrosequencing revealed hypermethylation of the H19/IGF2: intergenic differentially methylated region (IG DMR), also known as imprinting center 1 (IC1) and hypomethylation of the KCNQ1OT1: transcriptional start site (TSS) DMR (IC2). Array CGH demonstrated an 8 Mb duplication on chromosome 11p15.5p15.4 (205,827-8,150,933) and a 1 Mb deletion on chromosome 9p24.3 (209,020-1,288,114). Chromosome painting revealed that this duplication-deficiency in both patients is due to unbalanced segregation of a paternal reciprocal t(9;11)(p24.3;p15.4) translocation.

Conclusions
This is the first report of a paternally inherited unbalanced translocation between the chromosome 9 and 11 short arms underlying familial BWS. Copy number variations involving the 11p15.5 region are detected by the consensus diagnostic algorithm. However, in complex cases which do not only affect the BWS region itself, characterization of submicroscopic chromosome rearrangements can assist to estimate the recurrence risk and possible phenotypic outcomes.
KW  - Familial Beckwith-Wiedemann syndrome
KW  - copy number variation
KW  - duplication-deficiency
KW  - genomic imprinting
KW  - submicroscopic chromosome rearrangement
KW  - reciprocal translocation
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200422
VL  - 12
ER  -