Khan Samiullah, Mudassir Muhammad, Khan Naqab, Marwat Asmatullah
Dr. Samiullah Khan, Ph.D. Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan, KPK, Pakistan.
Mr. Muhammad Mudassir, M. Phil (Scholar). Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan, KPK, Pakistan.
Pak J Med Sci. 2018 Jan-Feb;34(1):82-87. doi: 10.12669/pjms.341.12885.
Brachdactyly a genetic disorder associated with the abnormal development of metacarpals, phalanges or both which results in the shortening of hands and feet. Mutations in the contributing genes has been recognized with the majority of the investigated syndromic form of brachdactyly. The current study was proposed to examine mutation in NOG and GDF5 genes in a Pakistani family.
Poly Acrylamide Gel Electrophoresis and Polymerase Chain Reaction was used for the genomic screening and linkage analysis to observe the mutation in genes. The samples were collected from Luckki Marwat district, KPK, while the research study was conducted in the department of Biochemistry, Quaid-I-Azam University, Islamabad, Pakistan.
After survey, family was identified with brachdactyly type A2 and investigated a heterozygous arginine to glutamine exchange in the growth demarcation factor 5 in all the victim persons. Different types of skeletal dysplasia resulted due to mutation in the GDF5 genes. Novel GDF5 genes mutations were reported with distinct limb malformation and sequencing of coding region revealed that the mildly affected individuals were heterozygous while the harshly affected individuals were homozygous.
The current study reported the genetic variability and concluded that the Brachdacytyly type A2 and type B2 resulted due to mutation in GDF5 and NOG genes respectively. A new subtype of brachydactyly (BDB2) was instigated as a result of novel mutations in NOG. The mutation has been reported for the first time in Pakistani population and especially in Pushtoon ethnic population.
短指症是一种与掌骨、指骨或两者异常发育相关的遗传性疾病，会导致手脚缩短。已确认相关基因的突变与大多数已研究的综合征型短指症有关。本研究旨在检测一个巴基斯坦家庭中NOG和GDF5基因的突变情况。
采用聚丙烯酰胺凝胶电泳和聚合酶链反应进行基因组筛查和连锁分析，以观察基因中的突变。样本采集自开伯尔-普赫图赫瓦省的卢基马尔瓦特地区，而研究工作在巴基斯坦伊斯兰堡的奎德-伊-阿扎姆大学的生物化学系进行。
经调查，该家庭被确定为A2型短指症，并在所有患病个体中发现生长分化因子5存在杂合的精氨酸到谷氨酰胺的交换。GDF5基因的突变导致了不同类型的骨骼发育异常。报告了新的GDF5基因突变，伴有明显的肢体畸形，编码区测序显示，轻度受影响的个体为杂合子，而重度受影响的个体为纯合子。
本研究报告了基因变异性，并得出结论，A2型和B2型短指症分别是由GDF5和NOG基因的突变导致的。由于NOG基因的新突变引发了一种新的短指症亚型（BDB2）。该突变首次在巴基斯坦人群中报道，尤其是在普什图族人群中。
