Bone Abstracts (2017) 6 P110 | DOI: 10.1530/boneabs.6.P110

Case report: a potentially new skeletal dysplasia with autosomal recessive inheritance

Caroline Lekszas1, Barbara Vona1, Indrajit Nanda1, Reza Maroofian2 & Thomas Haaf1


1Institute for Human Genetics, Julius Maximilians University, Würzburg, Germany; 2Monogenic Molecular Genetics, University of Exeter Medical School, Exeter EX1 2LU, UK.


Background: In this case report, we introduce a patient presenting a potentially unknown syndrome with skeletal involvement.

Presenting problem: At the time of physical examination, the boy was 10 years old, displaying short stature (z-score=−4.4), hearing loss, visual impairment, delayed eruption of teeth and severe dental caries, dysmorphic facial features, micrognathia, mild platyspondyly and genu valgum. Although he appears to have normal intelligence, he answers questions with delay and his school performance is poor, which may be linked to the hearing impairment. The patient is the only affected living child from a consanguineous Iranian couple. He has one unaffected sister. His parents have a history of multiple pregnancies that resulted in a spontaneous abortion, neonatal death or preterm termination due to skeletal malformations detected by ultrasound screening.

Clinical management: We performed whole exome sequencing (WES) using genomic DNA from the patient, one deceased affected sibling, as well as both parents using the Nextera Rapid Capture Enrichment library preparation protocol and the NextSeq500 desktop sequencer (Illumina). Data analysis was conducted with GensearchNGS, Exomiser and Phenomizer. By now, no putative causative variants in genes associated with initially suspected diseases like Stickler Syndrome and Schwartz-Jampel Syndrome were observed.

Discussion: Since our patient’s symptoms resemble a collagenopathy affecting the formation and maintenance of cartilage, we have primarily focused on analysing collagen type II, IX and XI genes. A holistic analysis aided through WES data from four family members will ensue. Following this strategy, we will be able to rapidly investigate genes associated with other collagenopathies and skeletal dysplasias in general, as well as their protein interaction partners (STRING). Notably, an article published in 2005 describes two affected brothers of consanguineous Turkish descent with remarkable phenotypic overlap with our patient. The authors performed mutation analysis of type I collagen genes, but were unable to identify a genetic cause for their patients’ disease. Due to the family’s clinical history and the negative result from the molecular genetic analysis that has been currently performed, we suspect a new collagenopathy with autosomal recessive inheritance and aim to identify a novel candidate gene from ongoing analyses.

Disclosure: The authors declared no competing interests.

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