Caselli R, Speciale C, Pescucci C, Uliana V, Sampieri K, Bruttini M, Longo I, De Francesco S, Pramparo T, Zuffardi O, Frezzotti R, Acquaviva A, Hadjistilianou T, Renieri A, Mari F
Medical Genetics, Department of Molecular Biology, University of Siena, Policlinico Le Scotte, V.le Bracci 2, 53100, Siena, Italy.
Department of Ophthalmology, Retinoblastoma Referral Center, Siena, Italy.
J Hum Genet. 2007;52(6):535-542. doi: 10.1007/s10038-007-0151-4. Epub 2007 May 15.
We describe three patients with retinoblastoma, dysmorphic features and developmental delay. Patients 1 and 2 have high and broad forehead, deeply grooved philtrum, thick anteverted lobes and thick helix. Patient 1 also has dolicocephaly, sacral pit/dimple and toe crowding; patient 2 shows intrauterine growth retardation and short fifth toe. Both patients have partial agenesis of corpus callosum. Patient 3 has growth retardation, microcephaly, thick lower lip and micrognathia. Using array-comparative genomic hybridization (CGH), we identified a 13q14 de novo deletion in patients 1 and 2, while patient 3 had a 7q11.21 maternally inherited deletion, probably not related to the disease. Our results confirm that a distinct facial phenotype is related to a 13q14 deletion. Patients with retinoblastoma and malformations without a peculiar facial phenotype may have a different deletion syndrome or a casual association of mental retardation and retinoblastoma. Using array-CGH, we defined a critical region for mental retardation and dysmorphic features. We compared this deletion with a smaller one in a patient with retinoblastoma (case 4) and identified two distinct critical regions, containing 30 genes. Four genes appear to be good functional candidates for the neurological phenotype: NUFIP1 (nuclear fragile X mental retardation protein 1), HTR2A (serotonin receptor 2A), PCDH8 (prothocaderin 8) and PCDH17 (prothocaderin 17).
我们描述了三名患有视网膜母细胞瘤、畸形特征和发育迟缓的患者。患者1和患者2前额高且宽、人中沟深、耳垂厚且前倾、耳轮厚。患者1还患有长头畸形、骶部凹陷/酒窝和脚趾拥挤；患者2表现为宫内生长迟缓及第五趾短小。两名患者均存在胼胝体部分发育不全。患者3有生长迟缓、小头畸形、下唇厚和小颌畸形。通过阵列比较基因组杂交（CGH），我们在患者1和患者2中鉴定出13q14新发缺失，而患者3有一个母系遗传的7q11.21缺失，可能与该疾病无关。我们的结果证实，一种独特的面部表型与13q14缺失有关。患有视网膜母细胞瘤且无特殊面部表型的畸形患者可能有不同的缺失综合征或智力发育迟缓与视网膜母细胞瘤的偶然关联。使用阵列CGH，我们确定了智力发育迟缓和畸形特征的关键区域。我们将此缺失与一名视网膜母细胞瘤患者（病例4）中的一个较小缺失进行比较，确定了两个不同的关键区域，包含30个基因。四个基因似乎是神经表型的良好功能候选基因：NUFIP1（核脆性X智力发育迟缓蛋白1）、HTR2A（血清素受体2A）、PCDH8（原钙黏蛋白8）和PCDH17（原钙黏蛋白17）。
