Morales C, Mademont-Soler I, Armengol L, Milà M, Badenas C, Andrés S, Soler A, Sánchez A
Servei de Bioquímica i Genètica Molecular, Hospital Clínic, Barcelona, Spain.
Cytogenet Genome Res. 2009;125(4):334-40. doi: 10.1159/000235940. Epub 2009 Oct 27.
Interstitial deletions of the short arm of chromosome 3 are rare, and a specific clinical phenotype has not been defined. We report the first isolated cryptic proximal interstitial 3p deletion, del(3)(p12.3p13), assessed by array-based comparative genomic hybridization in a girl with an inversion of chromosome 7, whose phenotype includes neurodevelopmental delay, growth retardation, dysmorphic facial features, hypophysis hypoplasia, gastroesophageal reflux, clinodactyly, preauricular appendix, and myopia. Her features are similar to those observed in the previously reported cases of proximal 3p deletions overlapping with our imbalance, indicating that her clinical manifestations are likely to be due to the deletion. As our patient's imbalance is the first non-cytogenetically visible proximal interstitial 3p deletion uncomplicated by other imbalances, its characterization has allowed us to narrow the minimal deletion interval associated with growth retardation and neurodevelopmental delay to the 3p12.3-p13 region. Among the genes found in this region, ROBO1, ROBO2, PDZRN3 and CNTN3 might play a role in the neurodevelopmental delay of the patient. This study provides additional evidence that cryptic imbalances anywhere along the genome can be found in patients with phenotypic abnormalities and a balanced chromosome rearrangement.
3号染色体短臂的间质性缺失较为罕见，且尚未明确其特定的临床表型。我们报告了首例经基于阵列的比较基因组杂交技术评估的孤立性隐匿性近端3p间质性缺失，即del(3)(p12.3p13)，该病例为一名患有7号染色体倒位的女孩，其表型包括神经发育迟缓、生长发育迟缓、面部畸形、垂体发育不全、胃食管反流、手指弯曲、耳前附件和近视。她的特征与先前报道的近端3p缺失病例中观察到的特征相似，这些病例与我们发现的失衡情况有重叠，这表明她的临床表现可能是由该缺失所致。由于我们患者的失衡是首例非细胞遗传学可见的近端间质性3p缺失，且未合并其他失衡情况，对其特征的描述使我们能够将与生长发育迟缓和神经发育迟缓相关的最小缺失区间缩小至3p12.3 - p13区域。在该区域发现的基因中，ROBO1、ROBO2、PDZRN3和CNTN3可能在该患者的神经发育迟缓中起作用。这项研究提供了更多证据，表明在具有表型异常和平衡染色体重排的患者中，基因组任何位置的隐匿性失衡都可能被发现。
