DPY19L2 Deletion as a Major Cause of Globozoospermia
DPY19L2 Deletion as a Major Cause of Globozoospermia
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DOI：
10.1016/j.ajhg.2011.01.018
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发表时间：
2011-03-11
影响因子：
9.8
通讯作者：
Viville, Stephane
中科院分区：
文献类型：
--
作者：
Koscinski, Isabelle;Ellnati, Elias;Viville, Stephane
球形精子症是一种罕见的（< 0.1%的男性不育患者）严重畸形精子症，主要由缺乏顶体的精子组成。研究一个约旦血缘家庭，其中五个兄弟被诊断为完全球形精子症，我们发现，四个分析的不育兄弟进行了纯合性缺失200 kb的12号染色体上，仅包含DPY19L2。在另外三名无关患者中发现了非常相似的缺失，这表明DPY19L2缺失是球形精子症的主要原因，因为19%（21例中的4例）的分析患者具有这种缺失。该缺失最可能是由于非等位基因同源重组（NAHR），因为该基因被两个低拷贝重复序列（LCR）包围。我们发现DPY19L2缺失的患者从三个不同的起源和两个不同的断点，强烈表明删除的结果与此基因座的特定建筑特征，而不是从创始人效应，而不完全排除最近的创始人效应的复发事件。DPY19L2与完整形式的球形精子症相关，与发现与球形精子症相关的前两个基因SPATA 16或PICK 1的情况一样。然而，与SPATA 16相反，没有妊娠报告，通过卵胞浆内精子注射，两名DPY 19 L2缺失的患者获得了妊娠，然后他们是三个孩子的父亲。
Globozoospermia, characterized by round-headed spermatozoa, is a rare (< 0.1% in male infertile patients) and severe teratozoospermia consisting primarily of spermatozoa lacking an acrosome. Studying a Jordanian consanguineous family in which five brothers were diagnosed with complete globozoospermia, we showed that the four out of five analyzed infertile brothers carried a homozygous deletion of 200 kb on chromosome 12 encompassing only DPY19L2. Very similar deletions were found in three additional unrelated patients, suggesting that DPY19L2 deletion is a major cause of globozoospermia, given that 19% (4 of 21) of the analyzed patients had such deletion. The deletion is most probably due to a nonallelic homologous recombination (NAHR), because the gene is surrounded by two low copy repeats (LCRs). We found DPY19L2 deletion in patients from three different origins and two different breakpoints, strongly suggesting that the deletion results from recurrent events linked to the specific architectural feature of this locus rather than from a founder effect, without fully excluding a recent founder effect. DPY19L2 is associated with a complete form of globozoospermia, as is the case for the first two genes found to be associated with globozoospermia, SPATA16 or PICK1. However, in contrast to SPATA16, for which no pregnancy was reported, pregnancies were achieved, via intracytoplasmic sperm injection, for two patients with DPY19L2 deletion, who then fathered three children.