A novel MTX2 gene splice site variant resulting in exon skipping, causing the recently described mandibuloacral dysplasia progeroid syndrome

Yeter Doğan B., Günay N., Ada Y., Doğan M. E.

American Journal of Medical Genetics, Part A, vol.191, no.1, pp.173-182, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 191 Issue: 1
  • Publication Date: 2023
  • Doi Number: 10.1002/ajmg.a.63010
  • Journal Name: American Journal of Medical Genetics, Part A
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, CAB Abstracts, EMBASE, MEDLINE
  • Page Numbers: pp.173-182
  • Keywords: exon skipping, mandibuloacral dysplasia progeroid syndrome, MDPS, Metaxin-2, MTX2, whole-exome sequencing, IGM NEPHROPATHY, ZMPSTE24, MUTATION, METALLOPROTEINASE, MEMBRANE, DISEASE, METAXIN, COMPLEX, MODEL
  • Kayseri University Affiliated: No


© 2022 Wiley Periodicals LLC.Until recently, mandibuloacral dysplasia (MAD) with type A and type B lipodystrophy was the first to come to mind in the association of mandibular hypoplasia, lipodystrophy, and acro-osteolysis. However, it has recently been added to the differential diagnosis of MAD, a newly defined syndrome, called MDPS. MDPS is a skeletal dysplasia characterized by postnatal growth retardation, hypotonia, generalized lipodystrophy, skin changes, progeroid traits, and dysmorphic facial features, including prominent eyes, long pinched nose, mandibular hypoplasia, and a small mouth. Biallelic null variants of the MTX2 gene are responsible for this syndrome. We performed whole-exome sequencing (WES) in a 6-year-old patient with skeletal dysplasia. WES revealed a novel homozygous c.543+1G>T splice site variant in the MTX2 gene. We also extracted total RNA from peripheral blood and used reverse transcription-polymerase chain reaction to generate cDNA. Sanger sequencing from cDNA showed that exon 8 of MTX2 was skipped. This study adds to the genetics and phenotype of MDPS and underlines the importance of comprehensive clinical and molecular research.