Two cases of autosomal dominant familial short stature associated with COL11A2 gene variant and the therapeutic response to recombinant human growth hormone.

Background: Variants in collagen genes can cause diverse growth plate disorders frequently associated with short stature. This study aimed to evaluate clinical phenotypes in two autosomal dominant familial short stature (AD-FSS), along with the responses to recombinant human growth hormone (rhGH).

Methods: Two AD-FSS children treated with rhGH from two families were included. Next-generation sequencing (NGS) was performed to screen the gene variants that may be related to short stature. The genetic test results were evaluated using the guidelines set by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP). The response of the children to rhGH was evaluated.

Results: The first case (child 1) was a girl aged 8 years and 7 months with a height of 118.8 cm. Her mother had a height of 145 cm. The child's maternal aunt, grandmother, grandmother's sisters, and great-grandmother were also under 150 cm in height, sharing the characteristic of short limbs. NGS revealed a c.688G>T heterozygous variant in exon 5 of the COL11A2 gene for the girl and her mother. The second case (child 2) was a boy aged 4 years and 8 months with a height of 96 cm. A heterozygous variant c.2458G>A in exon 32 of the COL11A2 gene was identified in the boy and his father. After 18 and 19 months of rhGH treatment, their heights increased by 15 and 20 cm, respectively, with no adverse events.

Conclusions: We presented two AD-FSS cases carrying the c.688G>T variant in exon 5 and the c.2458G>A variant in exon 32 of the COL11A2 gene, respectively. The short-term response to rhGH treatment is promising for AD-FSS children.