TRAPPC9-Related Intellectual Disability: Report of Two New Cases and Review of the Literature

Uctepe E., Yesilyurt A., Esen F. N., Tümer S., Mancllar H., Sonmez F. M.

Molecular Syndromology, cilt.14, sa.6, ss.485-492, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 14 Sayı: 6
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1159/000531439
  • Dergi Adı: Molecular Syndromology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.485-492
  • Anahtar Kelimeler: Array CGH, Autism, Exome sequencing, Intellectual disability, Microcephaly, TRAPPC9
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

Introduction: Hereditary forms of intellectual disability (ID), an estimated prevalence ranging between 1% and 3% in the general population, are among the most important problems in health care. Especially, autosomal-recessive ID has a very heterogeneous molecular basis and a lack of specific phenotypic features. Methods: Here, we report on two unrelated patients with autosomal-recessive ID, microcephaly, and autistic features and review the patients with TRAPPC9-related ID. Whole-exome sequencing and array CGH were performed for molecular diagnosis of the patients. Results: The first case has a microdeletion on chromosome 8q24.23-q24.3 region which is 1.7 Mb in length and includes the last 5 exons of TRAPPC9, and c.3435delG [p.Thr1146Profs∗8] deletion. The second case has a homozygous missense c.623A>C (p.His208Pro) variant in TRAPPC9 which is detected by means of whole-exome sequencing study of the proband. We also reviewed the clinical findings and mutation spectrum of all patients with TRAPPC9-related ID reported so far. Conclusions: Our study showed that the most consistent clinical findings for TRAPPC9-related ID are ID, microcephaly, and some structural brain MRI abnormalities. The mutations in the TRAPPC9 are scattered throughout all exons of TRAPPC9 indicating there is no hot spot mutation region in this gene.