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GROWTH PROMOTING THERAPIES MAYBE USEFUL IN SHORT STATURE PATIENTS WITH NON-SPECIFIC SKELETAL ABNORMALITIES CAUSED BY ACAN HETEROZYGOUS MUTATIONS: SIX CHINESE CASES AND LITERATURE REVIEW.

Objective: There are numerous reasons for short stature, including mutations in osteochondral development genes. ACAN, one such osteochondral development gene whose heterozygous mutations can cause short stature, has attracted attention from researchers in recent years. Therefore, we analysed six cases of short stature with heterozygous ACAN mutations and performed a literature review. Methods: Clinical information and blood samples from six probands and their family members were collected after consent forms were signed. Gene mutations in the probands were detected by whole-exome sequencing. Then, we searched the literature, performed statistical analysis and summarized the characteristics of all reported cases. Results: We identified six novel mutations of ACAN: c.1411C>T, c.1817C>A, c.1762C>T, c.2266G>C, c.7469G>A and c.1733-1G>A. In the literature, more than 200 affected individuals have been diagnosed genetically with a similar condition (height=-3.14±1.15 standard deviation score (SDS)). Among affected individuals receiving growth promoting treatment, their heights before and after treatment was -2.92±1.07 SDS vs. -2.14±1.23 SDS (p<0.001). As of July 1st, 2019, fifty-seven heterozygous ACAN mutations causing non-syndromic short stature had been reported, including the six novel mutations found in our study. Approximately half of these mutations can lead to protein truncation. Conclusions: This study used clinical and genetic means to examine the relationship between the ACAN gene and short stature. To some extent, clear diagnosis is difficult, since most of these affected individuals' characteristics are not prominent. Growth promoting therapies maybe beneficial for increasing their heights.