Autoimmune Polyglandular Syndrome Type 1: a case report
Autoimmune polyendocrinopathy syndrome type 1 (APS-1), also called autoimmune polyendocrinopathy-candidiasis–ectodermal dystrophy/dysplasia (APECED), is a rare autosomal recessive syndrome (OMIM 240300) with a small female preponderance. To define this syndrome, patients must have at least two of the three major components, i.e. a chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and autoimmune adrenal insufficiency. Other components of APS-1 include type 1 diabetes, autoimmune hepatitis, hypothyroidism, primary hypogonadism, pernicious anemia, alopecia, ectodermal dysplasia, malabsorption, and vitiligo.

The disease’s inheritance is in the Mendelian fashion. The underlying genetic abnormality which causes APS-1 is a mutation in the Autoimmune Regulator (AIRE) gene mapped to chromosome 21q22.3.

Researchers report a 19-year-old girl, who was born in an Iranian Muslim family with a clinical diagnosis of APS-1. To identify the causative mutation, a direct sequencing of the entire AIRE gene sequence was performed by Sanger sequencing method.

Three distinct variants were discovered, including c.1095 + 2 T greater than A, c.1197 T greater than C (rs1800521) and c.1578 T greater than C (rs1133779), in intron 9, exons 10 and 14 of the AIRE gene, respectively.

Her past medical history was significant for hypocalcemia-induced generalized tonic-clonic seizures (three episodes), when she was at the age of 6, due to hypoparathyroidism. At the age of 7, she was diagnosed with alopecia areata. She was suffering from asthma at the same time, for which she used salbutamol and montelukast. Her family history was remarkable for her parents’ consanguineous marriage, and also her sister death at the age of 14 years old, with no definitive diagnosis. Her sister had a history of blindness due to endophthalmitis and her symptoms before death were weakness, loss of appetite, fever, nauseas, and vomiting.

Multiple vertebral fractures, which results in spine deformity, were evident in her spine x-ray. Bone mineral densitometry (BMD) was performed which revealed osteoporosis.

The expression levels of the AIRE mRNA in PBMCs of the patient, her parents and her three siblings are shown in Fig. 1. According to this figure, compared to other family members with no sign of disease, the AIRE mRNA has been upregulated in the patient with a homozygous intron 9 mutation.

In conclusion, researchers identified three previously reported AIRE gene variations in an Iranian Muslim APS-1 patient. Furthermore, the association between c.1095 + 2 T > A mutation and APS-1 disease was confirmed in this report. Finally, AIRE gene expression analysis was performed, which indicated the functional impact of this variation for the first time. This study expands the diversity of variants that could cause APS-1. In addition to diagnostic utility, this information will help us better understand the pathophysiology of APS-1. More genetic studies are required to determine the frequency of these variants and their diagnostic credibility.

Source: https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-019-0870-3#Sec10
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