{Reference Type}: Case Reports
{Title}: A novel MTX2 gene splice site variant resulting in exon skipping, causing the recently described mandibuloacral dysplasia progeroid syndrome.
{Author}: Yeter Doğan B;Günay N;Ada Y;Doğan ME;
{Journal}: Am J Med Genet A
{Volume}: 191
{Issue}: 1
{Year}: Jan 2023
{Factor}: 2.578
{DOI}: 10.1002/ajmg.a.63010
{Abstract}: 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.