A novel MTX2 gene splice site variant resulting in exon skipping, causing the recently described mandibuloacral dysplasia progeroid syndrome
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, cilt.191, sa.1, ss.173-182, 2023 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 191 Sayı: 1
- Basım Tarihi: 2023
- Doi Numarası: 10.1002/ajmg.a.63010
- Dergi Adı: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, CAB Abstracts, EMBASE, MEDLINE
- Sayfa Sayıları: ss.173-182
- Anahtar Kelimeler: exon skipping, mandibuloacral dysplasia progeroid syndrome, MDPS, Metaxin-2, MTX2, whole-exome sequencing
- Erciyes Üniversitesi Adresli: Evet
Özet
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.