Deletions and pathogenic sequence variants in Myeloid Ecotropic Insertion Site 2 (MEIS2) gene have been reported to cause a recognizable triad of intellectual disability, congenital heart malformations, and palatal defects. To date, 18 individuals with de novo pathogenic sequence variants in MEIS2 have been reported in the literature, most with all three cardinal features. We recently saw a young boy, almost 3 years of age, who was known to have mosaic XYY syndrome (47,XYY [23]/46,XY[7]). He presented with atrial and ventricular septal defects, developmental delay, facial dysmorphism, gastroesophageal reflux, undescended testicle, a buried penis with penoscrotal transposition, primary neutropenia, and a branchial cleft sinus. Whole‐exome sequencing identified a previously reported in‐frame pathogenic deletion (c.998_1000delGAA; p.R333del; NM_170674.4) in MEIS2. His unaffected father was confirmed to have low‐level mosaicism for the same MEIS2 variant. The proband represents the 19th reported individual with a pathogenic sequence variant in MEIS2 and expands the phenotypic spectrum to include primary neutropenia, branchial anomalies, and complex genital anomalies. Furthermore, to our knowledge this is the first reported case of mosaicism for a variant in this gene in an apparently unaffected parent. This finding would have implications for recurrence risk counseling for families.

中文翻译：

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有智力障碍和心脏缺陷的儿童的MEIS2序列变异：扩展表型谱并记录未受影响父母的低水平镶嵌

据报道，髓系向生性插入位点2（MEIS2）基因中的缺失和致病性序列变异会导致可识别的三位智障，先天性心脏畸形和pa骨缺陷。迄今为止，有18个人在MEIS2中具有从头致病性序列变异在文献中已有报道，大多数具有全部三个基本特征。最近，我们看到了一个将近3岁的男孩，患有马赛克XYY综合征（47，XYY [23] / 46，XY [7]）。他表现出房间隔和室间隔缺损，发育迟缓，面部畸形，胃食管反流，睾丸未降，阴茎阴茎移位，原发性中性粒细胞减少和分支性c裂。全基因组测序确定了之前报道的在帧致病缺失（c.998_1000delGAA; p.R333del; NM_170674.4）的MEIS2。他未受影响的父亲被确认对同一MEIS2变体具有低水平的镶嵌性。先证者代表在MEIS2中具有致病性序列变异的第19个报告个体并将表型谱扩展到包括原发性中性粒细胞减少，分支异常和复杂的生殖器异常。此外，据我们所知，这是首次报道的在显然未受影响的亲本中该基因变异的嵌合体病例。这一发现将对家庭的复发风险咨询产生影响。