24781760 |
van Haelst et al (2015) describe two individuals wit MED13L mutations. Patient 1 showed delayed milestones, sandal gap toe, facial asymmetry and macroglossia. Patient 2 presented with recurrent ear infections, speech and motor delay, short stature, and mild retrognathia. Whole exome sequencing of Patient 1 and her parents identified a de novo splice acceptor mutation in exon 5 that resulted in the use of a cryptic splice acceptor site 45 nucleotides into exon 5. This 45 bp deletion is in a highly conserved region of the protein and was presumed to disrupt gene product function.
The analysis of Patient 2 by aCGH showed a 41 kb deletion of exons 6-20, also presumed to result in loss of function. |
25712080 |
Cafiero et al (2015) report three individuals with de novo pathogenic variants detected by whole exome sequencing. In one patient, a 1 bp deletion in exon 17 was predicted to result in premature termination. In a second patient, a single base pair insertion in exon 5 was also predicted to result in premature termination, and in a third patient, a stop-gain variant was found. All three mutations are predicted to result in haploinsufficiency.
The phenotypes of the patients is similar: dysmorphic features including a bulbous nasal tip with depressed nasal bridge, short mouth and straight eyebrows; developmental delay, motor delay, and intellectual disability. |
25106414 |
Asadollahi et al (2013) report two individuals with de novo intragenic deletions and one individual with a 1 Mb triplication of the whole gene plus MAP1LC3B2. The deletion patients showed hypotonia, moderate intellectual disability, conotruncal heart defects, and facial anomalies. Patient 1 had a 17 kb deletion of exon 2. In silico studies showed the deletion to be out of frame. Patient 2 had a 115 kb deletion of exons 3 and 4, which was de novo by qPCR.
Patient 3 showed a milder phenotype, with neonatal hypotonia, delayed walking and toilet training. Microarray using Affymetrix 6.0 platform showed a de novo 1 Mb triplication of all of MED13L and flanking gene, MAP1LC3B2. |
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