期刊
CLINICAL GENETICS
卷 95, 期 3, 页码 409-414出版社
WILEY
DOI: 10.1111/cge.13486
关键词
FIGLA; loss-of-function; mutation; premature ovarian insufficiency; short stature
资金
- 5010 project of Sun Yat-sen University [2014005]
- Fundamental Research Funds for the Central Universities [16ykjc15]
- National Key Research and development Program of China [2017YFC1001004]
- National Natural Science Foundation of China [81801431]
- science technology research project of Guangzhou city [2014YZ-00512]
Premature ovarian insufficiency (POI) is a group of heterogeneous disorders characterized by decreased ovarian reserve and increased follicle stimulating hormone (FSH) levels. It is rarely associated with short stature. FIGLA mutations with POI are identified with regard to heterozygosity; till date, only one affected family has been identified with homozygous mutations in FIGLA but without functional evaluation. Here, we described two POI patients from a consanguineous family from China. An 18-year-old girl and her sister presented with primary amenorrhea and increased FSH and luteinizing hormone levels, but the sister also presented with short stature and bone age delay. Whole-genome sequencing analysis identified a recurrent homozygous mutation in the FIGLA gene, c.2 T > C (p.Met1Thr), in this family member with POI; this variant was segregated within the pedigree. This change was absent in 382 control subjects, and we did not detect any mutations in 39 other idiopathic POI patients. in vitro functional analysis indicates that the p.Met1Thr mutation does not affect the transcription of the FIGLA gene, but blocks the synthesis of the full-length FIGLA protein. Our results support the notion that bi-allelic recessive loss-of-function effects of FIGLA contribute to POI patients with short stature and expand the FIGLA-related phenotypic spectrum.
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