Zollino Marcella, Seminara Laura, Orteschi Daniela, Gobbi Giuseppe, Giovannini Simona, Della Giustina Elvio, Frattini Daniele, Scarano Angela, Neri Giovanni
Istituto di Genetica Medica, Università Cattolica del S. Cuore, Roma, Italy.
Am J Med Genet A. 2009 Jun;149A(6):1116-24. doi: 10.1002/ajmg.a.32831.
The ring 14 (r14) syndrome is a rare condition, whose precise clinical and genetic characterization is still lacking. We analyzed a total of 20 patients with r14 and another 9 patients with a linear 14q deletion. The ring was complete, with no apparent loss of chromosome material, in 6 cases; a terminal 14q deletion, varying in size from 0.65 to 5 Mb, was detected in the remaining 14 cases. Deleted ring chromosomes were 70% paternal and 30% maternal. UPD (14) was never detected. With respect to the linear 14q deletions, three were proximal, varying in size from 4 to 7.2 Mb, and six distal, varying in size from 4.8 to 20 Mb. The majority of the linear deletions were also of paternal origin, and UPD (14) was excluded in all cases. Clinically, the r14 syndrome was characterized by a recognizable phenotype, consisting of shortness of stature, a distinctive facial appearance, microcephaly, scoliosis, and ocular abnormalities, which included abnormal retinal pigmentation, strabismus, glaucoma, and abnormal macula. All patients except one had mental retardation. Drug-resistant epilepsy was another highly consistent finding. Aggressive and hyperactive behavior was noted in about half of the patients. Based on genotype-phenotype correlations, we could deduce that retinal abnormalities, epilepsy, microcephaly, and mental retardation map within the proximal 14q11.2-q12 region. Likewise, behavior disorders and scoliosis could be assigned to the 14q32 region.
14号环状染色体（r14）综合征是一种罕见疾病，其确切的临床和遗传学特征仍不明确。我们共分析了20例r14患者以及另外9例14号染色体长臂线性缺失患者。6例患者的环状染色体完整，未见明显染色体物质丢失；其余14例检测到末端14号染色体长臂缺失，缺失大小从0.65至5 Mb不等。缺失的环状染色体70%来自父方，30%来自母方。未检测到单亲二倍体（UPD）（14）。关于线性14号染色体长臂缺失，3例为近端缺失，大小从4至7.2 Mb不等，6例为远端缺失，大小从4.8至20 Mb不等。大多数线性缺失也来自父方，所有病例均排除了UPD（14）。临床上，r14综合征具有可识别的表型，包括身材矮小、独特的面部外观、小头畸形、脊柱侧弯和眼部异常，眼部异常包括视网膜色素沉着异常、斜视、青光眼和黄斑异常。除1例患者外，所有患者均有智力障碍。耐药性癫痫是另一个高度一致的表现。约一半患者有攻击性行为和多动行为。基于基因型-表型相关性，我们可以推断视网膜异常、癫痫、小头畸形和智力障碍定位于近端14q11.2-q12区域。同样，行为障碍和脊柱侧弯可归因于14q32区域。
