Department of Child Health, Tokyo Kasei University, Tokyo, Japan; Department of Pediatrics, Tokyo Metropolitan Tobu Medical Center for Children with Developmental Disabilities, Tokyo, Japan.
Department of Pediatrics, Tokyo Metropolitan Tobu Medical Center for Children with Developmental Disabilities, Tokyo, Japan.
Eur J Med Genet. 2021 Nov;64(11):104332. doi: 10.1016/j.ejmg.2021.104332. Epub 2021 Sep 2.
Balanced chromosomal rearrangements with a breakpoint located upstream of the sex determining region Y-box 9 (SOX9) gene on chromosome 17q24.3 are associated with skeletal abnormalities, campomelic dysplasia (CMPD), or acampomelic campomelic dysplasia (ACMPD). We report on a female patient with a reciprocal translocation of t (11; 17) (p15.4; q24.3), who was diagnosed with acampomelic campomelic dysplasia. The 34-year-old Japanese patient presented with distinct skeletal abnormalities, profound intellectual disability, and female phenotype despite the presence of Y chromosome and the sex determining region Y (SRY) gene. Her menarche started at 33 years and 4 months after hormone therapy of estrogen therapy followed by estrogen progesterone therapy. By conducting whole genome sequencing followed by Sanger sequencing validation, we determined the precise breakpoint positions of the reciprocal translocation, one of which was located 203 kb upstream of the SOX9 gene. Considering the phenotypic variations previously reported among the CMPD/ACMPD patients with a chromosomal translocation in the vicinity of SOX9, the identified translocation was concluded to be responsible for all major phenotypes observed in the patient.
平衡染色体易位，断点位于 17q24.3 上的性别决定区 Y 框 9（SOX9）基因上游，与骨骼异常、campomelic 发育不良（CMPD）或非典型 campomelic 发育不良（ACMPD）有关。我们报告了一名女性患者，她患有 11；17（p15.4；q24.3）相互易位，被诊断为非典型 campomelic 发育不良。这名 34 岁的日本患者表现出明显的骨骼异常、严重的智力障碍和女性表型，尽管存在 Y 染色体和性别决定区 Y（SRY）基因。她的初潮在激素治疗雌激素治疗后 33 年 4 个月开始，然后进行雌激素孕激素治疗。通过进行全基因组测序，然后进行 Sanger 测序验证，我们确定了相互易位的精确断点位置，其中一个位于 SOX9 基因上游 203kb 处。考虑到之前报道的 SOX9 附近染色体易位的 CMPD/ACMPD 患者的表型变异，该鉴定的易位被认为是导致患者所有主要表型的原因。
