Both point mutations and deletions of the MYT1L gene as well as microdeletions of chromosome band 2p25.3 including MYT1L are associated with intellectual disability, obesity, and behavioral problems. Thus, MYT1L is assumed to be the-at least mainly-causative gene in the 2p25.3 deletion syndrome. Here, we present comprehensive descriptions of nine novel individuals bearing MYT1L mutations; most of them single nucleotide variants (SNVs). This increases the number of known individuals with causative deletions or SNVs of MYT1L to 51. Since eight of the nine novel patients bear mutations affecting MYT1L only, the total number of such individuals now nearly equals the number of individuals with larger microdeletions affecting additional genes, allowing for a comprehensive phenotypic comparison of these two patient groups. For example, 55% of the individuals with mutations affecting MYT1L only were overweight or obese as compared to 86% of the individuals with larger microdeletions. A similar trend was observed regarding short stature with 5 versus 35%, respectively. However, these differences were nominally significant only after correction for multiple testing, further supporting the hypothesis that MYT1L haploinsufficiency is central to the 2p25.3 deletion phenotype. Most importantly, the large number of individuals with MYT1L mutations presented and reviewed here allowed for the delineation of a more comprehensive clinical picture. Seizures, postnatal short stature, macrocephaly, and microcephaly could be shown to be over-represented among individuals with MYT1L mutations.

中文翻译：

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九个新发现的个体改善了与MYT1L突变相关的表型。

MYT1L基因的点突变和缺失以及包括MYT1L在内的2p25.3染色体条带的微缺失都与智力残疾，肥胖症和行为问题有关。因此，假定MYT1L是2p25.3缺失综合征中的至少是主要致病基因。在这里，我们介绍9个携带MYT1L突变的新个体的全面描述。其中大多数是单核苷酸变体（SNV）。这使具有MYT1L因果关系缺失或SNV的已知个体的数量增加到51个。由于9名新患者中有8个仅携带影响MYT1L的突变，因此，此类个体的总数现在几乎等于具有较大微缺失影响其他基因的个体的数量，可以对这两个患者群体进行全面的表型比较。例如，仅有55％的突变影响MYT1L的个体超重或肥胖，而微缺失较大的个体为86％。对于矮身材，观察到相似的趋势，分别为5％和35％。但是，这些差异只有在校正了多个测试后才在名义上有意义，进一步支持了MYT1L单倍体功能不足是2p25.3缺失表型的核心这一假说。最重要的是，此处介绍和综述的大量具有MYT1L突变的个体可以描绘出更全面的临床情况。癫痫发作，出生后身材矮小，大头畸形和小头畸形可能被证明在具有MYT1L突变的个体中过高。