TY - JOUR JF - ijmcmed JO - Int J Mol Cell Med VL - 8 IS - 4 PY - 2019 Y1 - 2019/11/01 TI - Utilization of Whole Exome Sequencing in Lethal Form of Multiple Pterygium Syndrome: Identification of Mutations in Embryonal Subunit of Acetylcholine Receptor TT - N2 - The acetylcholine receptor (AChR) is a member of the superfamily of transmitter-gated ion channels having a critical role in controlling electrical signals between nerves and muscle cells. Disruptive mutations in genes encoding different subunits of AChR result in multiple pterygium syndrome (MPS), which can be associated with a severe prenatally lethal presentation. This study aimed to investigate the etiology of lethal MPS (LMPS) in two consanguineous families with a history of miscarriages. DNA was extracted from a tissue sample of two aborted fetuses (probands) from two different families with a history of spontaneous miscarriages. Parental peripheral blood samples were collected for confirmatory analysis and follow-up testing. Whole-exome sequencing (WES) was performed on DNA from the probands. The results were confirmed and segregated by Sanger sequencing. Moreover, protein structure evaluations were accomplished. We identified a homozygous frameshift mutation of c.753_754delCT (p.V253fs*44) and a homozygous missense mutation of c.715C>T (p.Arg239Cys) in the CHRNG gene. Both aborted fetuses had pterygium, severe arthrogryposis, and fetal hydrops with cystic hygroma, being compatible with LMPS. The heterozygous state was confirmed in parents for both CHRNG variants. Likewise, CHRNG mutation was predicted to display the damaging effects by lowering the number of helixes and modifying the surface electrostatic potential. The present study identified rare sequence variants in the CHRNG gene in aborted fetuses from consanguineous couples with recurrent miscarriage history. WES is a comprehensive and cost-effective approach to study heterogeneous diseases including MPS. Such findings can improve our knowledge of MPS databases, particularly for genetic counseling of high-risk families and preimplantation genetic diagnosis. SP - 258 EP - 270 AU - Nazari, Tahere AU - Rashidi-Nezhad, Ali AU - Ganji, Maziar AU - Rezaei, Zahra AU - Talebi, Saeed AU - Ghasemi, Nasrin AU - Tavakkoly Bazzaz, Javad AD - Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. KW - Multiple pterygium syndromes KW - whole-exome sequencing KW - CHRNG KW - recurrent abortion UR - http://ijmcmed.org/article-1-1198-en.html DO - 10.22088/IJMCM.BUMS.8.4.258 ER -