The Raphael Recanati Genetics Institute, Rabin Medical Center, Petah Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Am J Med Genet A. 2023 Oct;191(10):2551-2557. doi: 10.1002/ajmg.a.63333. Epub 2023 Jun 26.
Proximal 1q21 microduplication is an incomplete penetrance and variable expressivity syndrome. This study reports 28 new cases and summarizes data on phenotype, gender, and parental origin. Data on isolated proximal 1q21.1 microduplications (g. chr1:145,394,956-145,762,959 GRCh37/hg19) was retrieved in postnatal and prenatal "clinical cases" group, and prenatal "control group." The "clinical cases" cases included cases where chromosomal microarray (CMA) was performed due to congenital anomalies, autism spectrum disorder, seizures, and developmental delay/intellectual disability. The "control group" cases consisted of fetal CMA performed upon parental request despite normal nuchal translucency and anatomical second trimester fetal scans. We analyzed a local database of 27,990 cases and another cohort of 80,000 cases (including both indicated and non-indicated cases) for population frequency analysis. A total of 62 heterozygous cases were found, including 28 index cases and 34 family members. Among the index cases, 13 (9 males, 4 females) were identified in the "clinical cases" group, of which 10 had developmental abnormalities. Parental origin was tested in 9/13 cases, and all were found to be maternally inherited. In the "control group," which comprised non-affected cases, of 15 cases (10 males, 5 females), only 5/11 were maternally inherited. Four cases with clinical follow-up showed no reported neurodevelopmental abnormalities. No de-novo cases were detected, and the population frequency in both cohorts was 1:1000. Proximal 1q21.1 microduplication is a recurrent copy number variant, associated with neurodevelopmental abnormalities. It has a greater impact on males inheriting it from their mothers than females from their fathers.
1q21 近端微重复是一种不完全外显率和表现度可变的综合征。本研究报道了 28 例新病例，并总结了表型、性别和亲本来源的数据。在“临床病例”组和产前“对照组”中检索了孤立的近端 1q21.1 微重复（g.chr1:145,394,956-145,762,959 GRCh37/hg19）的出生后和产前数据。“临床病例”组的病例包括由于先天性异常、自闭症谱系障碍、癫痫发作和发育迟缓/智力残疾而进行染色体微阵列（CMA）的病例。“对照组”组的病例由父母要求进行胎儿 CMA 组成，尽管颈项透明层正常且进行了第二次妊娠中期胎儿扫描。我们分析了 27990 例的本地数据库和另一个 80000 例（包括指示性和非指示性病例）的队列进行人群频率分析。共发现 62 例杂合病例，包括 28 例指数病例和 34 例家族成员。在指数病例中，有 13 例（9 名男性，4 名女性）在“临床病例”组中被发现，其中 10 例存在发育异常。对 9/13 例进行了亲本来源测试，结果均为母系遗传。在由非受累病例组成的“对照组”中，有 15 例（10 名男性，5 名女性），仅 5/11 例为母系遗传。有 4 例具有临床随访，未报告神经发育异常。未检测到新生病例，两个队列的人群频率均为 1:1000。近端 1q21.1 微重复是一种反复出现的拷贝数变异，与神经发育异常有关。从母亲那里继承它的男性比从父亲那里继承它的女性受到更大的影响。
