关键词: ACAN基因； 矮小症； 生长激素

Abstract: Objective ACAN gene is one of the most frequently mutated genes in familial short stature (FSS), which has key roles in endochondral ossification and maintaining the biological function of cartilage. To observe the efficacy of recombinant human growth hormone (rhGH) for increasing the height of children of FSS with ACAN gene variants. Methods Clinical data obtained from 2 pedigrees of FSS caused by ACAN gene variants at our institution were retrospectively analyzed. Relevant electronic databases were searched for studies assessing the therapeutic effect of rhGH in children of FSS with ACAN gene variants. Results? The proband of family 1 was a 4 -year and 1 -month-old boy and without skeletal deformity, when his height was 90 . 5 cm (-3 . 6 SD) and weight 13 . 5 kg. His bone age was 5 years and 6 months. Genetic testing identified a heterozygous deletion mutation in ACAN gene (c. 5026 _ 5027 del, p. Ser 1676 Ter). His height increased by 13 cm (Ht: 103 . 5 cm, -1 . 8 SD) in the first year of treatment with rhGH ( 50 μg·kg- 1 ·d- 1 ) and height increased by 17 . 1 cm (Ht: 107 . 6 cm, -1 . 7 SD) after 18 months of treatment. The proband of family 2 was a 3-year-old boy without skeletal deformity, when his height was 82cm (-3.9 SD) and weight 12 kg. His bone age was 1 year and 6 months. Genetic testing identified a heterozygous missense mutation in ACAN gene (c.1504C>T, p.R502C). His height increased by 12cm (Ht:94cm, -2.6 SD) in the first year of treatment with rhGH (33 μg·kg- 1 ·d- 1 ) and height increased by 17 cm (Ht: 99 cm, -2 . 68 SD) after 22 months of treatment. Conclusion? Heterozygous deletion mutation(c.5026 _ 5027 del) and heterozygous missense mutation(c.1504 C>T) of ACAN gene can cause FSS. rhGH therapy can effectively improve the height of children of FSS with ACAN gene variants in the short term. It is recommended to detect gene in patients of FSS and to treat the disease with rhGH as early as possible.

Key words: ACAN gene; short stature; growth hormone