PMID- 28145517 OWN - NLM STAT- MEDLINE DCOM- 20181022 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 DP - 2017 Feb 1 TI - Whole Genome Sequencing Identifies Novel Compound Heterozygous Lysosomal Trafficking Regulator Gene Mutations Associated with Autosomal Recessive Chediak-Higashi Syndrome. PG - 41308 LID - 10.1038/srep41308 [doi] LID - 41308 AB - Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease characterized by varying degrees of oculocutaneous albinism, recurrent infections, and a mild bleeding tendency, with late neurologic dysfunction. This syndrome is molecularly characterized by pathognomonic mutations in the LYST (lysosomal trafficking regulator). Using whole genome sequencing (WGS) we attempted to identify novel mutations of CHS based on a family of CHS with atypical symptoms. The two patients demonstrated a phenotypic constellation including partial oculocutaneous albinism, frequency upper respiratory infection or a marginal intelligence, without bleeding tendency and severe immunodeficiency. WGS revealed two compound LYST mutations including a maternally inherited chr1:235969126G > A (rs80338652) and a novel paternally inherited chr1: 235915327A > AT, associated with autosomal recessive CHS. These two variants fall in the coding regions of LYST, resulting in premature truncation of LYST due to R1104X/N2535KfsX2 induced incomplete translation. Notably, the heterozygous carriers (i.e. parents) were unaffected. Our finding also reveals decreased plasma serotonin levels in patients with CHS compared with unaffected individuals for the first time. The present study contributes to improved understanding of the causes of this disease and provides new ideas for possible treatments. FAU - Jin, Yaqiong AU - Jin Y AD - Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. AD - Biobank for Clinical Data and Samples in Pediatric, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Zhang, Li AU - Zhang L AD - Center for Bioinformatics and Computational Biology, and the Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China. FAU - Wang, Senfen AU - Wang S AD - Department of Dermatology, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Chen, Feng AU - Chen F AD - Department of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Gu, Yang AU - Gu Y AD - Department of Dermatology, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Hong, Enyu AU - Hong E AD - Biobank for Clinical Data and Samples in Pediatric, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Yu, Yongbo AU - Yu Y AD - Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Ni, Xin AU - Ni X AD - Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. AD - Biobank for Clinical Data and Samples in Pediatric, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. AD - Department of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Guo, Yongli AU - Guo Y AD - Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. AD - Biobank for Clinical Data and Samples in Pediatric, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. FAU - Shi, Tieliu AU - Shi T AD - Center for Bioinformatics and Computational Biology, and the Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, China. FAU - Xu, Zigang AU - Xu Z AD - Department of Dermatology, Beijing Children's Hospital, Capital Medical University, Beijing, China. LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170201 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (LYST protein, human) RN - 0 (Vesicular Transport Proteins) RN - 333DO1RDJY (Serotonin) SB - IM MH - Alleles MH - Amino Acid Sequence MH - Base Sequence MH - Chediak-Higashi Syndrome/blood/*genetics MH - Child MH - DNA Mutational Analysis MH - Female MH - Heterozygote MH - Humans MH - Infant MH - Male MH - Mutation/*genetics MH - Pedigree MH - Reproducibility of Results MH - Serotonin/blood MH - Vesicular Transport Proteins/chemistry/*genetics MH - *Whole Genome Sequencing PMC - PMC5286514 COIS- The authors declare no competing financial interests. EDAT- 2017/02/02 06:00 MHDA- 2018/10/23 06:00 PMCR- 2017/02/01 CRDT- 2017/02/02 06:00 PHST- 2016/08/31 00:00 [received] PHST- 2016/12/16 00:00 [accepted] PHST- 2017/02/02 06:00 [entrez] PHST- 2017/02/02 06:00 [pubmed] PHST- 2018/10/23 06:00 [medline] PHST- 2017/02/01 00:00 [pmc-release] AID - srep41308 [pii] AID - 10.1038/srep41308 [doi] PST - epublish SO - Sci Rep. 2017 Feb 1;7:41308. doi: 10.1038/srep41308.