ESPE Abstracts

Objective: To explore the genetic basis for a Chinese three-generations pedigree affected with Severe Short Stature with a mild form of Geleophysic Dysplasia Type 2（GD2）

Methods: We collected 11 related family members from a Chinese 3-generation pedigree with severe short stature with a mild form of Geleophysic Dysplasia Type 2 GD2. Clinical data of the 11 family members was collected．With genomic DNA extracted from the peripheral blood samples of 5 of the seven patients, potential mutation was detected by targeted exome sequencing．Candidate variants were validated by Sanger sequencing and bioinformatic analysis．

Results: Seven patients showed severe and disproportionate short stature with normal birth weight and birth length. They had shown progressive postnatal growth failure with normal developmental milestones and normal cognition and no distinct facial features. The patient Ⅱ1 male adult height 139cm（-5.52SD） with a markedly elevated sitting height/leg length(SH/LL) 1.438(+4.3SD). He once experienced balloon dilatation due to pulmonary stenosis. A skeletal survey was normal. Targeted exome sequencing and Sanger sequencing revealed a missense c.5099A>G(P.Tyr1700Cys) variant in the exon 42 of FBNl gene in 5 of the seven patients, which was reported in patients with Acromicric Dysplasia (AD)．Bioinformatics analysis suggested that the variant can cause amino acid replacement and affect the structure and function of fibrillin-1．

Conclusion: A missense variant of the FBNl gene was identified，which probably underlies the autosomal dominant severe and disproportionate short stature with a mild form of GeleophysicDysplasia Type 2（GD2）in this pedigree．