Deng Ruizhi, McCalman Melysia T, Bossuyt Thomas P, Barakat Tahsin Stefan
Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, Netherlands.
Front Genet. 2021 Sep 1;12:716874. doi: 10.3389/fgene.2021.716874. eCollection 2021.
Interstitial deletions on the long arm of chromosome 12 (12q deletions) are rare, and are associated with intellectual disability, developmental delay, failure to thrive and congenital anomalies. The precise genotype-phenotype correlations of different deletions has not been completely resolved. Ascertaining individuals with overlapping deletions and complex phenotypes may help to identify causative genes and improve understanding of 12q deletion syndromes. We here describe two individuals with non-overlapping 12q14 deletions encountered at our clinical genetics outpatient clinic and perform a review of all previously published interstitial 12q deletions to further delineate genotype-phenotype correlations. Both individuals presented with a neurodevelopmental disorder with various degrees of intellectual disability, failure to thrive and dysmorphic features. Previously, larger deletions overlapping large parts of the deletions encountered in both individuals have been described. Whereas, individual 1 seems to fit into the previously described phenotypic spectrum of the 12q14 microdeletion syndrome, individual 2 displays more severe neurological symptoms, which are likely caused by haploinsufficiency of the BAF complex member , which is included in the deletion. We furthermore perform a review of all previously published interstitial 12q deletions which we found to cluster amongst 5 regions on chromosome 12, to further delineate genotype-phenotype correlations, and we discuss likely disease relevant genes for each of these deletion clusters. Together, this expands knowledge on deletions on chromosome 12q which might facilitate patient counseling. Also, it illustrates that re-analysis of previously described microdeletions syndromes in the next generation sequencing era can be useful to delineate genotype-phenotype correlations and identify disease relevant genes in individuals with neurodevelopmental disorders.
12号染色体长臂的间质缺失（12q缺失）较为罕见，与智力残疾、发育迟缓、生长发育不良及先天性异常有关。不同缺失的精确基因型-表型相关性尚未完全明确。确定具有重叠缺失和复杂表型的个体可能有助于识别致病基因并增进对12q缺失综合征的理解。我们在此描述了在我们临床遗传学门诊遇到的两名具有非重叠12q14缺失的个体，并对所有先前发表的间质12q缺失进行了综述，以进一步明确基因型-表型相关性。两名个体均表现为神经发育障碍，伴有不同程度的智力残疾、生长发育不良和畸形特征。此前，已描述过与这两名个体所遇缺失大部分区域重叠的更大缺失。个体1似乎符合先前描述的12q14微缺失综合征的表型谱，而个体2表现出更严重的神经症状，这可能是由缺失中包含的BAF复合体成员单倍剂量不足所致。我们还对所有先前发表的间质12q缺失进行了综述，发现这些缺失聚集在12号染色体的5个区域，以进一步明确基因型-表型相关性，并讨论每个缺失簇可能的疾病相关基因。总之，这扩展了对12q染色体缺失的认识，可能有助于患者咨询。此外，这表明在新一代测序时代对先前描述的微缺失综合征进行重新分析，对于明确基因型-表型相关性以及识别神经发育障碍个体中的疾病相关基因可能是有用的。
