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A novel nonsense mutation in ADAMTS17 caused autosomal recessive inheritance Weill–Marchesani syndrome from a Chinese family

  • Yi, Haoan1
  • Zha, Xu2
  • Zhu, Yuechun3
  • Lv, Jin4
  • Hu, Shouzhi4
  • Kong, Yanbo2
  • Wu, Guojiu2
  • Yang, Yuling1
  • He, Yongshu1
  • 1 Kunming Medical University, Department of Cell Biology and Medical Genetics, Kunming, Yunnan Province, China , Kunming (China)
  • 2 the 2nd Affiliated Hospital of Kunming Medical University, Department of Ophthalmology, Kunming, Yunnan Province, China , Kunming (China)
  • 3 Kunming Medical University, Department of Biochemstry and Molecular Biology, Kunming, Yunnan Province, China , Kunming (China)
  • 4 the First People’s Hospital of Qujing City, Department of Ophthalmology, Qujing, Yunnan Province, China , Qujing (China)
Published Article
Journal of Human Genetics
Springer Nature
Publication Date
Apr 25, 2019
DOI: 10.1038/s10038-019-0608-2
Springer Nature


Weill–Marchesani syndrome (WMS) is a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, eye anomalies, including microspherophakia, ectopia of the lenses, severe myopia, glaucoma and occasionally heart defects. Given these complex clinical manifestations and genetic heterogeneity, WMS patients presented misdiagnosed as high myopia or angle closure glaucoma. Here, we report ADAMTS17 mutations, a member of the extracellular matrix protease family, from a Chinese family. Patients have features that fall within the WMS spectrum. The exome (protein-coding regions of the genome) makes up ~1 % of the genome, it contains about 85% of known disease-related variants. Whole exome sequencing (WES) has been performed to identify the disease-associated genes, including one patient, his healthy sister, and his asymptomatic wife. Genome-wide homozygosity map was used to identify the disease caused locus. SNVs and INDELs were further predicted with MutationTaster, LRT, SIFT and SiPhy and compared to dbSNP150 and 1000 Genomes project. Filtered mutation was confirmed with Sanger sequencing in whole family members. The Genome-wide homozygosity map based on WES identified a total of 20 locus which were possible pathogenic. Further, a novel nonsense mutation c.1051A >T result in p.(lys351Ter) in ADAMTS17 had been identified in a candidate loci. The Sanger sequencing data has verified two consanguineous WMS patients in the family pedigree and revealed autosomal recessive (AR) inheritance pattern. The nonsense mutation in ADAMTS17 was analyzed in silico to explore its effects on protein function. We predicted the mutation produced non-function protein sequence. A novel nonsense mutation c.1051 A > T in ADAMTS17 had been identified caused autosomal recessive WMS in the Chinese family.

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