Role of the prenatal diagnosis of SRPS-5 neonate caused by compound heterozygous mutation of WDR35 by Trio-WES

doi:10.3969/j.issn.1673-8640.2022.010.004

Abstract

Abstract:

Objective To investigate the role of prenatal diagnosis of a neonate of short-rib polydactyly syndrome-5（SRPS-5） induced by a compound heterozygous mutation of WDR35 by trio-whole exome sequencing （trio-WES）. Methods The clinical data of prenatal diagnosis of a neonate were collected. The genes of induced labor tissues and parents were determined by trio-WES. The biohazard analysis of the suspicious variant was carried out by using SIFT，PolyPhen-2 and Mutation Taster software，and the model was established to predict the protein structure changes caused by the mutation. Results At 22⁺³ weeks of gestation，ultrasound examination showed that fetal limb long bone had developmental delay，with bilateral humerus and femur bending，narrow chest cavity and reduced chest circumference，shortened ribs and compressed lungs. The gene test showed that there were compound heterozygous mutations in WDR35 in fetus，which were heterozygous mutation in father（c.799G>A/p.Val267Met） and loss of heterozygous mutation in chr2：20151176-2015124 in mother. The 2 mutations searched from PubMed and HGMD databases had not been reported. There were new mutations of WDR35. The c.799G>A/p.Val267Met was highly conserved among species，and the prediction of protein structure suggested that it might change the local spatial stability. Conclusions The defect of WDR35 may be the pathogenic factor of the fetal long bone shortening with bending，short rib with lung dysplasia and other symptoms，and the accurate diagnosis of SRPS-5 can be made by trio-WES.

Key words: WDR35, Short rib-polydactyly syndrome, Short-rib thoracic dysplasia 5, Trio-whole exome sequencing, Prenatal diagnosis

ZHAO Xuliang, TIAN Ruixia, SHI Youwen, YU Min, JIAO Liuliu, ZHU Fuxi. Role of the prenatal diagnosis of SRPS-5 neonate caused by compound heterozygous mutation of WDR35 by Trio-WES[J]. Laboratory Medicine, 2022, 37(10): 928-933.

Figures/Tables 5

References 21

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