一例先天性孤立性促肾上腺皮质激素缺乏症患儿的TBX19基因变异分析

目的分析一例先天性孤立性促肾上腺皮质激素缺乏症(isolated adrenocorticotropic hormone deficiency,IAD)患儿的临床及遗传学特点。方法回顾性分析1例先天性IAD患儿的临床特点,通过全外显子测序对患儿家系进行基因检测。结果基因检测结果显示患儿携带TBX19基因c.535C>T(p.R179X)和c.298C>T(p.R100C)复合杂合变异,其中c.535C>T(p.R179X)遗传自父亲,为已报道的致病性变异;c.298C>T(p.R100C)遗传自母亲,既往未见报道。结论先天性IAD临床缺乏特异性,TBX19基因检测是确诊的关键。

Analysis of TBX19 gene variant in a child with congenital isolated adrenocorticotropic hormone deficiency

Objective To analyze the clinical and genetic characteristics of a patient with congenital isolated adrenocorticotropic hormone deficiency(IAD).Methods Clinical characteristics of the patient was reviewed.Genomic DNA of the child was subjected to whole exome sequencing.Results Genetic testing has confirmed the diagnosis of congenital IAD by identification of compound heterozygous variants of the TBX19 gene,which included a pathogenic nonsense c.535C>T(p.R179X)variant inherited from his father and a novel missense c.298C>T(p.R100C)variant inherited from his mother.Conclusion Congenital IAD due to variants of the TBX19 gene is a rare autosomal recessive disease.It is characterized by low plasma adrenocorticotropic hormone and cortisol levels but normal levels of other pituitary hormones.Delayed diagnosis may lead to severe early-onset adrenal failure and wrong treatment which may result in neonatal mortality.Hydrocortisone replacement is effective.Detection of pathogenic variant of TBX19 gene is the key to diagnosis.