Faculty of Medicine, Al-Neelain University, Khartoum, Sudan.
INSERM UMR 1141 PROTECT, Université Paris Diderot- Sorbonne Paris Cité, Paris, France.
BMC Med Genomics. 2022 Nov 8;15(1):236. doi: 10.1186/s12920-022-01354-1.
The etiology of intellectual disabilities is diverse and includes both genetic and environmental factors. The genetic causes of intellectual disabilities range from chromosomal aberrations to single gene disorders. The TRAPPC9 gene has been reported to cause autosomal recessive forms of intellectual disabilities in 56 patients from consanguineous and non-consanguineous families around the world.
We analyzed two siblings with intellectual disability, microcephaly and delayed motor and speech development from a consanguineous Sudanese family. Genomic DNA was screened for mutations using NGS panel (NextSeq500 Illumina) testing 173 microcephaly associated genes in the Molecular Genetics service in Robert Debre hospital in Paris, France.
A novel homozygous mutation (NM_031466.7 (TRAPPC9):c.2288dup, p. (Val764Glyfs*7) in exon 14 of TRAPPC9 gene was found in the two patients. The mutation was predicted to cause nonsense mediated decay (NSMD) using SIFT prediction tool. The variant has not been found in either gnomAD or Exac databases. Both parents were heterozygous (carriers) to the mutation.
This is the first study to report patients with TRAPPC9-related disorder from Sub-Saharan Africa.
智力障碍的病因多种多样，包括遗传和环境因素。智力障碍的遗传原因从染色体异常到单基因疾病不等。TRAPPC9 基因已在来自世界各地的 56 名近亲繁殖和非近亲繁殖的患者中被报道为常染色体隐性形式的智力障碍的原因。
我们分析了来自苏丹一个近亲家庭的 2 名智力障碍、小头畸形和运动及言语发育迟缓的兄弟姐妹。使用 NGS 面板（NextSeq500 Illumina）在法国巴黎罗伯特·德布雷医院的分子遗传学服务中对 173 个与小头畸形相关的基因进行基因突变筛查。
在这两名患者中发现了 TRAPPC9 基因第 14 外显子中一个新的纯合突变（NM_031466.7 (TRAPPC9):c.2288dup, p. (Val764Glyfs*7)。SIFT 预测工具预测该突变会导致无义介导的衰变（NSMD）。该变体在 gnomAD 或 Exac 数据库中均未找到。父母双方均为该突变的杂合子（携带者）。
这是第一项来自撒哈拉以南非洲的 TRAPPC9 相关疾病患者的研究。
