论文部分内容阅读
目的探讨先天性类脂质性肾上腺增生症(congenital lipoid adrenal hyperplasia,CLAH)患儿的临床及分子遗传学特征。方法选取1例2016年10月本院收治的20天龄女性CLAH患儿的临床资料,进行染色体核型分析,SRY基因检测,并提取标准家系成员外周血DNA,采用目标序列基因捕获芯片联合下一代高通量测序(next generation sequencing,NGS)对肾上腺皮质功能低下相关基因进行分析,对获选的变异位点进行Sanger测序验证,并对家系成员进行共分离验证。结果患儿皮肤色素沉着,男性性反转,呕吐,高血钾,低血钠,促肾上腺皮质激素水平增高,染色体核型46XY,SRY基因阳性,腹股沟区及盆腔彩超探及睾丸声像,St AR基因复合杂合突变c.772G>A(Q258X)、c.179-15G>T(NM-000349.2),父母分别为突变位点的携带者,符合常染色体隐性遗传。c.179-15G>T突变以往未见文献报道,该位点位于5’UTR区,对外显子部分有调控作用,推测可能影响外显子的正常剪切,很可能致病。结论本病例具有典型的临床表型,c.179-15G>T可能是中国人中St AR基因的一种新突变,Q258X和c.179-15G>T复合杂合突变可使St AR蛋白功能丧失而引起CLAH。开展NGS有助于从分子层面对单基因突变所致肾上腺皮质功能低下的病因进行鉴别,明确CLAH诊断。
Objective To investigate the clinical and molecular genetic features of children with congenital lipoid adrenal hyperplasia (CLAH). Methods A clinical data of a 20-day-old female with CLAH admitted to our hospital in October 2016 was selected for chromosome karyotype analysis and SRY gene detection. DNA from peripheral blood of standard pedigrees was extracted and combined with target gene capture chip A generation of next generation sequencing (NGS) was used to analyze genes associated with adrenal insufficiency. Sanger sequencing was performed on the selected mutated sites and co-segregation of members of the pedigree was verified. Results Children with skin pigmentation, male sexual inversion, vomiting, hyperkalemia, hyponatremia, elevated levels of adrenocorticotropic hormone, chromosomal karyotype 46XY, SRY gene positive, groin area and pelvic color ultrasound and testicular sonography, St AR gene heterozygous heterozygous mutation c.772G> A (Q258X), c.179-15G> T (NM-000349.2), respectively, the parents of the mutation site carriers, in line with autosomal recessive inheritance. c.179-15G> T mutation has not been reported in the past, the site is located in the 5’UTR region, the exonic part of regulation, presumably may affect the normal exon shearing, is likely to cause disease. Conclusion This case has a typical clinical phenotype, c.179-15G> T may be a new mutation of St AR gene in Chinese, Q258X and c.179-15G> T complex heterozygous mutation can make St AR protein function Loss caused by CLAH. To carry out NGS helps to identify the cause of adrenocortical hypomorphism caused by single-gene mutation from the molecular level and confirm the diagnosis of CLAH.