A chinese boy with geleophysic dysplasia caused by compound heterozygous mutations in ADAMTSL2

Geleophysic dysplasia, belonging to the group of acromelic dysplasia, is a rare genetic disease. Two genes, FBN1 and ADAMTSL2, were known to be linked to this disorder. The disorder presents as extreme short stature, short limbs, small hands and feet, stubby fingers and toes, joint stiffness, toe walking, skin thickening, progressive cardiac valvular thickening and characteristic facial features, including a round face with full cheeks. Here, we report the first Chinese case with geleophysic dysplasia type 1 based on clinical and genetic features. The boy was admitted because of severe physical growth retardation and mild motor retardation. Comprehensive medical evaluations were performed including metabolic studies, endocrine function examination, bone X-rays and echocardiography. Much delayed bone age and geleophysic dysplasia were found. Targeted next-generation sequencing was used to detect genetic mutations associated with skeletal dysplasia. Sanger sequencing was used to confirm the mutations in the patient. PCR amplification, cloing, and sequencing was used to determine the de novo mutation origin. Two compound heterozygous mutations were confirmed in the ADAMTSL2 gene of the patient. The c.340G > A (p.Glu114Lys) mutation was a de novo heterozygous mutation, and our results suggested that it was located on the paternal allele. While the c.234-2A > G inherited from his mother was a novel pathogenic heterozygous splicing mutation. Growth hormone deficiency had been observed in the patient. His growth velocity was improved by growth hormone supplementation. In conclusion, we have identified a novel splicing mutation of ADAMTSL2 carried by a Chinese boy with geleophysic dysplasia type 1. The patient was treated effectively with growth hormone supplementation.