Khan Hammal, Ahmed Sohail, Nawaz Sadia, Ahmad Wasim, Rafiq Muhammad Arshad
Department of Biosciences, COMSATS University, Islamabad, Pakistan.
Institute of Biochemistry, University of Balochistan, Quetta, Pakistan.
Klin Padiatr. 2021 Mar;233(2):53-58. doi: 10.1055/a-1223-2489. Epub 2020 Dec 18.
GLI3 is a transcriptional regulator of several genes involved in mammalian skeletal development. Mutations in the pleiotropic gene GLI3 may result in different inherited disorders including Greig cephalopolysyndactyly syndrome (GCPS). GCPS is characterized by mild to severe craniofacial and limb malformations.
Here, we report clinical and molecular study of 3 families with GCPS originated in different regions of Pakistan. Sanger sequencing revealed two novel variants including a frameshift [c. 3790_3791InsC, p.(Gly1236Argfs11)] and a missense [c.1692A>G, p.(His536Arg)], and one previously reported variant [c.1965_1966delAT, p.(His627Glufs48)] located in 2 different domains of the GLI3.
This study not only expanded spectrum of the mutations in the but also highlighted phenotypic variability in the GCPS patients. This will facilitate diagnosis and genetic counseling of families with same and related disorders in the Pakistani population.
GLI3是参与哺乳动物骨骼发育的多个基因的转录调节因子。多效性基因GLI3的突变可能导致不同的遗传性疾病，包括Greig头多指综合征（GCPS）。GCPS的特征是轻至重度的颅面和肢体畸形。
在此，我们报告了对源自巴基斯坦不同地区的3个GCPS家系的临床和分子研究。桑格测序揭示了两个新变体，包括一个移码突变[c. 3790_3791InsC，p.(Gly1236Argfs11)]和一个错义突变[c.1692A>G，p.(His536Arg)]，以及一个先前报道的位于GLI3的2个不同结构域的变体[c.1965_1966delAT，p.(His627Glufs48)]。
本研究不仅扩展了GLI3突变谱，还突出了GCPS患者的表型变异性。这将有助于巴基斯坦人群中患有相同及相关疾病家庭的诊断和遗传咨询。
