目的：探讨15q11.2 BP1-BP2片段拷贝数变异的性质及其在产前诊断咨询中的相关问题。方法：回顾因智力精神障碍来我院产前诊断中心就诊的76例病例和1 955例因其他原因就诊行染色体微阵列分析的对照病例，将其分为智力精神障碍患者组、中枢神经系统异常产前检查组及非中枢神经系统异常产前检查组，对携带15q11.2 BP1-BP2片段拷贝数变异的病例进行变异来源的验证和随访；对3组缺失病例的检出率进行统计学分析。结果：智力精神障碍患者组未见携带15q11.2 BP1-BP2片段拷贝数变异的病例；中枢神经系统异常产前检查组有2例携带该拷贝数变异的病例，其中1例是新发突变；非中枢神经系统异常产前检查组有15例携带该拷贝数变异的病例，均为父母遗传而来。携带拷贝数变异的胎儿及中枢神经系统异常产前检查组出生的胎儿目前生长精神运动均与标准符合，17例病例的父母也无异常，将对其持续随访。非中枢神经系统异常产前检查组缺失病例的检出率与智力精神障碍患者组及文献中病人组缺失的检出率相比，差异均无统计学意义，P>0.05。结论：鉴于本研究及文献回顾中15q11.2 BP1-BP2片段单纯缺失的低外显度特征不宜定义为病理性变异，但需要更多研究证实，故在产前诊断的报告与咨询中需慎重；而该片段重复被认为良性变异可能性大。

[1] CHEN C P,LIN S P,LEE C L,et al.Familial transmission of recurrent 15q11.2(BP1-BP2) microdeletion encompassing NIPA1,NIPA2,CYFIP1,and TUBGCP5 associated with phenotypic variability in developmental,speech,and motor delay[J].Taiwan J Obstet Gynecol,2017,56(1):93-97.
[2] BULTER M G,BITTEL D C,KIBIRYEVA N,et al.Behavioral differences among subjects with Prader-Willi syndrome and type Ⅰ or type Ⅱ deletion and maternal disomy[J].Pediatrics,2004,113(3Pt1):565-573.
[3] PICINELLI C,LINTAS C,PIRAS I S,et al.Recurrent 15q11.2 BP1-BP2 microdeletions and microduplications in the etiology of neurodevelopmental disorders[J].Am J Med Genet B Neuropsychiatr Genet,2016,171(8):1088-1098.
[4] 程双喜,赖雪芳,詹文.0~6岁儿童神经心理发育量表在儿童智力障碍诊断中的临床应用[J].中国实用医药,2017,12(10):42-44.
[5] 孙彦香,高武红,黄彦科,等.晚期早产儿神经发育预后及影响因素分析[J].现代医学,2015,43(4):424-427.
[6] MURTHY S K,NYGREN A O,El H M,et al.Detection of a novel familial deletion of four genes between BP1 and BP2 of the Prader-Willi/Angelman syndrome critical region by oligo-array CGH in a child with neurological disorder and speech impairment[J].Cytogenet Genome Res,2007,116(1-2):135-140.
[7] COOPER G M,COE B P,GIRIRAJAN S,et al.A copy number variation morbidity map of developmental delay[J].Nat Genet,2011,43(9):838-846.
[8] DOORNBOS M,SIKKEMA B,RUIJVENKAMP C A,et al.Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader-Willi critical region,possibly associated with behavioural disturbances[J].Eur J Med Genet,2009,52(2-3):108-115.
[9] KOVEL C G,TRUCKS H,HELBIG I,et al.Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies[J].Brain,2010,133(Pt1):23-32.
[10] BUTLER M G.Clinical and genetic aspects of the 15q11.2 BP1-BP2 microdeletion disorder[J].J Intellect Disabil Res,2017,61(6):568-579.
[11] ROSENFELD J A,COE B P,EICHLER E E,et al.Estimates of penetrance for recurrent pathogenic copy-number variations[J].Genet Med,2013,15(6):478-481.
[12] VANLERBERGHE C,PETIT F,MALAN V,et al.15q11.2 microdeletion (BP1-BP2) and developmental delay,behaviour issues,epilepsy and congenital heart disease:a series of 52 patients[J].Eur J Med Genet,2015,58(3):140-147.
[13] CHASTE P,SANDERS S J,MOHAN K N,et al.Modest impact on risk for autism spectrum disorder of rare copy number variants at 15q11.2,specifically breakpoints 1 to 2[J].Autism Res,2014,7(3):355-362.
[14] ULFARSSON M O,WALTERS G B,GUSTAFSSON O,et al.15q11.2 CNV affects cognitive,structural and functional correlates of dyslexia and dyscalculia[J].Transl Psychiatry,2017,7(4):e1109.
[15] BURNSIDE R D,PASION R,MIKHAIL F,et al.Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2:a susceptibility region for neurological dysfunction including developmental and language delay[J].Hum Genet,2011,130(4):517-528.
[16] CAROL G,DIANA W,MARK D K,et al.Recommendations for the use of chromosome microarray in pregnancy[J].RCOP,2015,Web:www.rcpath.org.
[17] VAN D Z B,STAAL W G,HOCHSTENBACH R,et al.A co-segregating microduplication of chromosome 15q11.2 pinpoints two risk genes for autism spectrum disorder[J].Am J Med Genet B Neuropsychiatr Genet,2010,153B(4):960-966.