University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, Texas, USA.
School of Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
Am J Med Genet A. 2023 Jul;191(7):1990-1993. doi: 10.1002/ajmg.a.63214. Epub 2023 Apr 17.
Pathogenic variants in TRAF7 are often de novo and features of individuals harboring these variants are characterized by neurodevelopmental delay, ptosis, cardiac defects, limb anomalies, and dysmorphic features. We present a familial case in two African American patients with a novel, likely pathogenic c.1936G>A variant in TRAF7. Patient 1 is a 31-year-old female with a patent ductus arteriosus (PDA), intellectual disability, ptosis, and other dysmorphic features. She was identified to harbor this likely pathogenic variant in a mosaic (33.89%) state in leukocytes. Her son, Patient 2, is a 10-month-old male with a PDA, atrial septal defect, ptosis, developmental delay, history of feeding difficulties, congenital maxillary frenulum, and malrotation of the intestine. He has the same variant in a non-mosaic state. These cases demonstrate the variable expressivity observed with variants in TRAF7 within the same family and expand upon current understanding of mosaic TRAF7 variants. They also provide phenotypic data on genetic variation in individuals with African American ancestry, a population who has been underrepresented in the literature and may be less frequently referred to genetic specialists.
TRAF7 中的致病性变异通常是新生的，携带这些变异的个体的特征是神经发育迟缓、上睑下垂、心脏缺陷、肢体异常和畸形特征。我们报告了一个非洲裔美国人家系中的两个病例，这两个病例均携带 TRAF7 中的一个新的、可能致病性的 c.1936G>A 变异。患者 1 是一名 31 岁女性，患有动脉导管未闭（PDA）、智力障碍、上睑下垂和其他畸形特征。她在白细胞中以镶嵌（33.89%）状态携带这种可能致病性变异。她的儿子，患者 2，是一名 10 个月大的男性，患有 PDA、房间隔缺损、上睑下垂、发育迟缓、喂养困难史、先天性上颌系带和肠旋转不良。他在非镶嵌状态下具有相同的变异。这些病例表明，在同一个家族中，TRAF7 中的变异存在可变表达，并扩展了对镶嵌 TRAF7 变异的现有认识。它们还提供了具有非洲裔美国人血统的个体中遗传变异的表型数据，该人群在文献中代表性不足，可能较少被转介给遗传专家。
