Sasongko Teguh Haryo, Yusoff Surini, Atif Amin Baig, Fatemeh Hayati, Rani Abdulqawee, Marini Marzuki, Ab Aziz Che Badariah, Zabidi-Hussin Z A M H, Nishio Hisahide, Zilfalil Bin Alwi
Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia.
Brain Dev. 2010 May;32(5):385-9. doi: 10.1016/j.braindev.2009.06.008. Epub 2009 Aug 6.
The majority of spinal muscular atrophy (SMA) patients showed homozygous deletion or other mutations of SMN1. However, the genetic etiology of a significant number of SMA patients has not been clarified. Recently, mutation in the gene underlying cat SMA, limb expression 1 (LIX1), has been reported. Similarity in clinical and pathological features of cat and human SMA may give an insight into possible similarity of the genetic etiology.
In this study, we screened for a mutation in LIX1 using direct DNA sequencing in our SMA and/or SMA-like patients who retained SMN1. A total of 33 patients were enrolled in this study, of which 22 were Japanese and 11 were Malaysians. All these patients possessed at least two copies of SMN1.
We did not identify any pathogenic mutations in the coding regions or splice sites of LIX1 in the patients. In addition, we described a polymorphism within LIX1 intron 3, c.387+107A>T. We found that A-allele is significantly more frequent in SMA patients compared to normal individuals.
Molecular genetic analysis of our SMA and/or SMA-like patients suggests that LIX1 is not associated with the development of their disorders. However, the number of patients analyzed in this study was very limited, and a larger study with bigger sample size is needed to confirm this result.
大多数脊髓性肌萎缩症（SMA）患者表现出SMN1基因的纯合缺失或其他突变。然而，相当数量的SMA患者的遗传病因尚未明确。最近，有报道称猫SMA的潜在基因——肢体表达1（LIX1）发生了突变。猫和人类SMA在临床和病理特征上的相似性可能有助于深入了解遗传病因的可能相似性。
在本研究中，我们对保留SMN1的SMA和/或类SMA患者采用直接DNA测序法筛查LIX1基因的突变。本研究共纳入33例患者，其中22例为日本人，11例为马来西亚人。所有这些患者均至少拥有两份SMN1拷贝。
我们在患者的LIX1编码区或剪接位点未发现任何致病突变。此外，我们描述了LIX1内含子3中的一个多态性，即c.387 + 107A>T。我们发现，与正常个体相比，SMA患者中A等位基因的频率显著更高。
对我们的SMA和/或类SMA患者进行的分子遗传学分析表明，LIX1与他们疾病的发生无关。然而，本研究分析的患者数量非常有限，需要进行更大样本量的更大规模研究来证实这一结果。
