Endocrine Abstracts

GAPO syndrome (OMIM 230740) is a rare, multiple congenital anomalies syndrome characterized by Growth retardation, Alopecia, Pseudoanodontia and Ocular manifestations. Syndrome caused by anthrax toxin receptor 1 (ANTXR1) gene (NM_032208.2) mutation leading to deficiency of an enzyme involved in the metabolism and breakdown of extracellular matrix (ECM). Disease show parental consanguinity, autosomal recessive inheritance and since first description in 1947 a total of 38 patients have been reported to date. Lack of the breakdown result dyshistogenic sequence of the ECM and deposition of those materials in the multiple organs. Affected patients have short stature, distinctive craniofacial features, typical facial appearance, ocular manifestations and maldeveloped teeth. Hypergonadotropic hypogonadism may be seen due to extensive deposition of the extracellular material in the female reproductive organs. In this study; we introduce a young Syrian woman, with typical phenotypic appearance and clinical features of the GAPO syndrome, admitted with primary amenorrhea. Her endocrinological investigations showed hypergonadotropic hypogonadism prominent with elevated FSH, LH and low estradiol and progesterone. Patient had no parental consanguinity and by direct sequencing of the ANTXR1 gene, we identified a novel homozygous splicing variation (c.152+1G>T in intron 1) in the patient. This variant has not been previously reported in the Human Gene Mutation Database (HGMD; http://www.hgmd.cf.ac.uk/ac/index.php) and in population studies (ExAC: Exome Aggregation Consortium and 1000 Genomes Project). Our findings expand the spectrum of causative mutations and clinical findings in GAPO Syndrome.