Shu-Han You1, Yun-Shien Lee2, Chueh-Pai Lee3, Chih-Peng Lin4, Chiao-Yun Lin5, Chia-Lung Tsai6, Yao-Lung Chang1, Po-Jen Cheng1, Tzu-Hao Wang7, Shuenn-Dyh Chang8. 1. Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-Kou Medical Center, Tao-Yuan 333, Taiwan. 2. Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan; Department of Biotechnology, Min-Chuan University, Tao-Yuan 333, Taiwan. 3. Bioinformatics Division, Yourgene Bioscience Inc., New Taipei City, Taiwan. 4. Department of Biotechnology, Min-Chuan University, Tao-Yuan 333, Taiwan; Bioinformatics Division, Yourgene Bioscience Inc., New Taipei City, Taiwan. 5. Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-Kou Medical Center, Tao-Yuan 333, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan. 6. Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan. 7. Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-Kou Medical Center, Tao-Yuan 333, Taiwan; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan; College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan. 8. Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-Kou Medical Center, Tao-Yuan 333, Taiwan. Electronic address: gene@cgmh.org.tw.
Abstract
OBJECTIVE: Single-nucleotide polymorphism (SNP) microarrays and whole-exome sequencing (WES) are tools to precisely diagnose rare autosomal recessive (AR) diseases. In this study, SNP chip and WES were used to identify a mutated location in WDR34 in a baby born to consanguineous parents. CASE REPORT: The baby, born at 36 gestational weeks had a small thoracic cage, symmetric short proximal bones, and polydactyly. Radiography showed short ribs with reduced lung volume and pulmonary opacities, compatible with asphyxiating thoracic dystrophy or short rib-polydactyly syndrome (SRPS). At 4 months of age, she died of pulmonary hypoplasia and sepsis. SNP microarray and evaluation tool confirmed WDR34 as the candidate gene. WES detected an AR mutation at c.554C > T [p.Arg182Trp] in WDR34. CONCLUSION: This study was the first to identify c.544C > T [p.Arg182Trp] mutation in WDR34 in a patient with SRPS. According to the database, the homozygous mutation of c.544C > T in WDR34 was deleterious and the prevalence of heterozygous mutation was relatively higher in Asian population. More studies of this mutation in patients with SRPS are required.
OBJECTIVE: Single-nucleotide polymorphism (SNP) microarrays and whole-exome sequencing (WES) are tools to precisely diagnose rare autosomal recessive (AR) diseases. In this study, SNP chip and WES were used to identify a mutated location in WDR34 in a baby born to consanguineous parents. CASE REPORT: The baby, born at 36 gestational weeks had a small thoracic cage, symmetric short proximal bones, and polydactyly. Radiography showed short ribs with reduced lung volume and pulmonary opacities, compatible with asphyxiating thoracic dystrophy or short rib-polydactyly syndrome (SRPS). At 4 months of age, she died of pulmonary hypoplasia and sepsis. SNP microarray and evaluation tool confirmed WDR34 as the candidate gene. WES detected an AR mutation at c.554C > T [p.Arg182Trp] in WDR34. CONCLUSION: This study was the first to identify c.544C > T [p.Arg182Trp] mutation in WDR34 in a patient with SRPS. According to the database, the homozygous mutation of c.544C > T in WDR34 was deleterious and the prevalence of heterozygous mutation was relatively higher in Asian population. More studies of this mutation in patients with SRPS are required.