NRXN1 deletion syndrome; phenotypic and penetrance data from 34 families
NRXN1 deletion syndrome; phenotypic and penetrance data from 34 families
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DOI：
10.1016/j.ejmg.2018.07.015
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发表时间：
2019-03-01
影响因子：
1.9
通讯作者：
Lynch, Sally A.
中科院分区：
文献类型：
--
作者：
Al Shehhi, Maryam;Forman, Eva B.;Lynch, Sally A.
与neurexin-1（NRXN 1）杂合缺失相关的表型谱是多样的，包括：孤独症谱系障碍、注意缺陷多动障碍、智力残疾、癫痫发作、精神分裂症、情绪障碍和先天性畸形。该基因缺失的降低的重复率和可变的表达率仍然是遗传咨询的挑战。我们对来自34个家族的67个NRXN 1缺失进行了临床回顾，以记录表型并确定比值比。最初从临床转诊至arrayCGH的队列中确定了34例先证者（5例成人，29例儿童（< 16岁））。在级联筛选后，从家族中鉴定出另外33个NRXN 1缺失（16个具有确定的表型）。言语和语言延迟是一致的临床表现。遗传组的谱系分析显示，许多未经测试的亲属有精神健康和发育问题的历史，最明显的是NRXN 1 β亚型患者。我们的研究强调了NRXN 1表型在这一人群中的复杂性。
The spectrum of phenotypes associated with heterozygous deletions of neurexin-1 (NRXN1) is diverse and includes: autism spectrum disorder, attention deficit hyperactivity disorder, intellectual disability, seizures, schizophrenia, mood disorders and congenital malformations. Reduced penetrance and variable expressivity of deletions in this gene remain a challenge for genetic counselling. We clinically reviewed 67 NRXN1 deletions from 34 families to document the phenotype and determine odds ratio. Thirty-four probands (5 adults, 29 children ( < 16 years)) were initially identified from a cohort clinically referred for arrayCGH. A further 33 NRXN1 deletions (16 with established phenotype) from the families were identified following cascade screening. Speech and language delay was a consistent clinical presentation. Pedigree analysis of the inherited group revealed numerous untested relatives with a history of mental health and developmental issues, most notably in the NRXN1 beta isoform patients. Our study highlights the complex nature of the NRXN1 phenotype in this population.