Prontera Paolo, Bernardini Laura, Stangoni Gabriela, Capalbo Anna, Rogaia Daniela, Ardisia Carmela, Novelli Antonio, Dallapiccola Bruno, Donti Emilio
Medical Genetics Unit, University of Perugia, Perugia, Italy.
Am J Med Genet A. 2009 Feb 15;149A(4):706-12. doi: 10.1002/ajmg.a.32688.
A 36-year-old patient with a disorder characterized by severe mental retardation, behavioral problems, dysmorphic face, "muscular build," and hand/foot anomalies, is reported. Following a diagnosis of de novo pericentric inversion of chromosome 8 based on standard cytogenetic analysis, a subsequent 75 kb array-CGH investigation disclosed a deletion spanning for about 13.7 Mb in the 2q31.2q32.3 region. Whole painting of chromosome 8 established the intrachromosomal nature of the rearrangement and FISH analysis with locus-specific probes confirmed the deletion on the long arm of chromosome 2. The deleted region, clinical outcome, and medical history in this patient are mainly superimposable to those reported in a published 8-year-old boy, suggesting that this genomic segment is prone to rearrangements and its hemizygosity gives rise to a clinically recognizable syndrome. The role of some genes mapping in the deleted region and related with distinct disorders is discussed. Interestingly, deletion of MSTN gene, a negative regulator of muscle growth, was associated in our patient with a "muscular build," a feature which could be regarded as a handle for clinical recognition of this syndrome.
报道了一名36岁患者，其病症表现为严重智力发育迟缓、行为问题、面部畸形、“肌肉发达体型”以及手足异常。基于标准细胞遗传学分析诊断为8号染色体新发臂间倒位后，随后的75 kb阵列比较基因组杂交（array-CGH）研究发现2q31.2q32.3区域存在一个约13.7 Mb的缺失。8号染色体的全染色体涂染确定了重排的染色体内性质，使用位点特异性探针的荧光原位杂交（FISH）分析证实了2号染色体长臂上的缺失。该患者的缺失区域、临床结果和病史与一名已发表的8岁男孩所报道的情况主要重叠，表明该基因组片段易于重排，其半合子状态导致了一种临床上可识别的综合征。讨论了一些定位于缺失区域且与不同疾病相关的基因的作用。有趣的是，肌肉生长负调节因子MSTN基因的缺失在我们的患者中与“肌肉发达体型”相关，这一特征可被视为该综合征临床识别的线索。
