Title |
Segregation between SMCHD1 mutation, D4Z4 hypomethylation and Facio-Scapulo-Humeral Dystrophy: a case report
|
---|---|
Published in |
BMC Medical Genomics, September 2016
|
DOI | 10.1186/s12881-016-0328-9 |
Pubmed ID | |
Authors |
Marie-Cécile Gaillard, Francesca Puppo, Stéphane Roche, Camille Dion, Emmanuelle Salort Campana, Virginie Mariot, Charlene Chaix, Catherine Vovan, Killian Mazaleyrat, Armand Tasmadjian, Rafaelle Bernard, Julie Dumonceaux, Shahram Attarian, Nicolas Lévy, Karine Nguyen, Frédérique Magdinier, Marc Bartoli |
Abstract |
The main form of Facio-Scapulo-Humeral muscular Dystrophy is linked to copy number reduction of the 4q D4Z4 macrosatellite (FSHD1). In 5 % of cases, FSHD phenotype appears in the absence of D4Z4 reduction (FSHD2). In 70-80 % of these patients, variants of the SMCHD1 gene segregate with 4qA haplotypes and D4Z4 hypomethylation. We report a family presenting with neuromuscular symptoms reminiscent of FSHD but without D4Z4 copy reduction. We characterized the 4q35 region using molecular combing, searched for mutation in the SMCHD1 gene and determined D4Z4 methylation level by sodium bisulfite sequencing. We further investigated the impact of the SMCHD1 mutation at the protein level and on the NMD-dependent degradation of transcript. In muscle, we observe moderate but significant reduction in D4Z4 methylation, not correlated with DUX4-fl expression. Exome sequencing revealed a heterozygous insertion of 7 bp in exon 37 of the SMCHD1 gene producing a loss of frame with premature stop codon 4 amino acids after the insertion (c.4614-4615insTATAATA). Both wild-type and mutated transcripts are detected. The truncated protein is absent and the full-length protein level is similar in patients and controls indicating that in this family, FSHD is not associated with SMCHD1 haploinsufficiency. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 1 | 25% |
Unknown | 3 | 75% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 75% |
Scientists | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 1 | 7% |
Unknown | 14 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 4 | 27% |
Professor > Associate Professor | 2 | 13% |
Student > Ph. D. Student | 2 | 13% |
Student > Master | 2 | 13% |
Student > Bachelor | 1 | 7% |
Other | 1 | 7% |
Unknown | 3 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 3 | 20% |
Medicine and Dentistry | 3 | 20% |
Biochemistry, Genetics and Molecular Biology | 2 | 13% |
Computer Science | 1 | 7% |
Nursing and Health Professions | 1 | 7% |
Other | 0 | 0% |
Unknown | 5 | 33% |