Mohamad Shah Nurul Syazana, Salahshourifar Iman, Sulong Sarina, Wan Sulaiman Wan Azman, Halim Ahmad Sukari
Reconstructive Science Unit, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University, Isfahan, Iran.
BMC Genet. 2016 Feb 11;17:39. doi: 10.1186/s12863-016-0345-x.
Nonsyndromic orofacial clefts are one of the most common birth defects worldwide. It occurs as a result of genetic or environmental factors. This study investigates the genetic contribution to nonsyndromic cleft lip and/or palate through the analysis of family pedigrees. Candidate genes associated with the condition were identified from large extended families from the Malay population.
A significant nonparametric linkage (NPL) score was detected in family 100. Other suggestive NPL and logarithm of the odds (LOD) scores were attained from families 50, 58, 99 and 100 under autosomal recessive mode. Heterogeneity LOD (HLOD) score ≥ 1 was determined for all families, confirming genetic heterogeneity of the population and indicating that a proportion of families might be linked to each other. Several candidate genes in linkage intervals were determined; LPHN2 at 1p31, SATB2 at 2q33.1-q35, PVRL3 at 3q13.3, COL21A1 at 6p12.1, FOXP2 at 7q22.3-q33, FOXG1 and HECTD1 at 14q12 and TOX3 at 16q12.1.
We have identified several novel and known candidate genes for nonsyndromic cleft lip and/or palate through genome-wide linkage analysis. Further analysis of the involvement of these genes in the condition will shed light on the disease mechanism. Comprehensive genetic testing of the candidate genes is warranted.
非综合征性口面部裂隙是全球最常见的出生缺陷之一。它是由遗传或环境因素导致的。本研究通过分析家系来调查非综合征性唇裂和/或腭裂的遗传贡献。从马来人群的大型扩展家系中鉴定出与该病症相关的候选基因。
在100号家庭中检测到显著的非参数连锁（NPL）分数。在常染色体隐性模式下，50号、58号、99号和100号家庭也获得了其他提示性的NPL和优势对数（LOD）分数。所有家庭的异质性LOD（HLOD）分数≥1，证实了人群的遗传异质性，并表明一部分家庭可能相互连锁。确定了连锁区间内的几个候选基因；1p31处的LPHN2、2q33.1 - q35处的SATB2、3q13.3处的PVRL3、6p12.1处的COL21A1、7q22.3 - q33处的FOXP2、14q12处的FOXG1和HECTD1以及16q12.1处的TOX3。
我们通过全基因组连锁分析确定了几个非综合征性唇裂和/或腭裂的新的和已知的候选基因。进一步分析这些基因在该病症中的作用将有助于揭示疾病机制。对候选基因进行全面的基因检测是必要的。
