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Bone Abstracts (2017) 6 LB20 | DOI: 10.1530/boneabs.6.LB20

ICCBH2017 Late Breaking Oral Communication Abstracts (1) (21 abstracts)

COL2A1 c.1609G>A (p.Gly537Ser) a pathogenic variant causing multiple skeletal abnormalities and severe short stature

Elpis Vlachopapadopoulou 1 , Irene Dikaiakou 1 , Emmanouil Manolakos 2 , Ioannis Panagiotopoulos 1 & Stefanos Michalacos 1

1Chldren’s Hospital P.A. Kyriakoy, Athens, Greece; 2Access To Genome Clinical Laboratory, Athens, Greece.

Background: Skeletal dysplasias include many pathological conditions that involve bone metabolism and health and most of them are associated with short stature. 211 genes are associated with bone dysplasia and short stature.

Presenting problem: To present a boy with severe short stature and skeletal abnormalities. He was born at term AGA. Growth failure was noted from the age of 8 months. IGF-I levels were low and he was tested for growth hormone deficiency (GHD). GHD was diagnosed, so he was treated with GH. He had poor response and GH therapy was discontinued. On physical examination a significant lordosis was appreciated and bone x-rays revealed flattening of the pelvic bones and flattening and deformities of the vertebrae. Family history was significant for short stature of the father (150 cms) with bone deformities.

Methods: NGS exome study was carried out on DNA obtained from peripheral blood, in order to identify genomic variants in 211 genes associated with bone dysplasia and short stature. The panel used for the preparation of the library has been designed by SureSelectXT Human All Exon V5 (Agilent Technologies), it captures (>19000 genes,>350000 exons, >85% of the alterations responsible for genetic diseases) and the splicing flanking (5 bp) regions, its size is ~50Mb. Sequencing was performed with the HiSDefault 2500 SystemTM (Illumina) sequencer. The reads obtained were filtered, based on quality parameters, and aligned to the reference genome (build 37 of genome Hg19), using the BWA (version 0.7.12) alignment program.

Results: Genetic variants identified in this study are listed in the following table:

Segregation studies in order to determine the inheritance pattern of the identified variant were done and the same variant was identified at the father.

Conclusions: The presence of mutations in COL2A1 has been associated, with an autosomal dominant inheritance pattern, with different chondrodysplasias and spondyloepihyseal dysplasia. The variant COL2A1 c.1609G>A (p.Gly537Ser) identified in heterozygosity in the patient, is considered a pathogenic variant and has been previously registered in HGMD associated to spondyloepiphyseal dysplasia (accession:CM052184) [1].

Genomic position and genotype Gene/Transcript Nucleotide Change/Aminoacid change dbSNP ID/ExAC. Freq. Exon/Effect Zygosity(1)/ Variant Freq. In silico Pred.(2) Categorization of the variant(3)
Chr12:48379582 C/T COL2A1 NM_001844.4 c.1609G>A p.Gly537Ser Exon 25 missense Het 42% 8 Pathogenic

Disclosure: The authors declared no competing interests

Volume 6

8th International Conference on Children's Bone Health


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