Molecular Genetic Study Of The Family Of Patients With Congenital Adrenal Hyperplasia

Objective: The aim of this study was to make a definite diagnosis by bioinformatics analysis of patients and their families who were suspected of congenital adrenal hyperplasia?CAH?.To explore whether there are new gene mutations in CAH and the correlation between the genotype and phenotype.Methods: From July 2017 to December 2018,hospitalized patients with suspected congenital adrenocortical hyperplasia in the Endocrinology Department of the people's Hospital of Xinjiang Uygur Autonomous region in combination with biochemical tests,clinical manifestations,medical history and signs were select in this research.The patients with CAH were set up as probands,and their families were set up as family group,male and female?gender?.Blood collection,DNA extraction,PCR amplification,gene sequencing and MLPA detection were performed.The result of gene sequences were compared and analyzed,the pathogenic sites and new sites were found,and the biological information of mutation sites was analyzed.Result: A total of 3 patients were clinically diagnosed with CAH?2 of 3 with 21-hydroxylase deficiency and 1 of 3 with 17-hydroxylase deficiency?were evaluated.The results of gene mutation detection in 2 patients with 21-hydroxylase deficiency confirmed by genotyping.However,no abnormal mutations were found in the patient with 17-hydroxylase deficiency.Family data of proband were collected.the results showed that the CYP21A2 gene of the proband indicated a compound heterozygous mutation: c.[T710?T713A of c.T518 A p.Ile173Asn?Het?,E6/CDS6 of E4/CDS4;T719A] p.[Ile237Asn;Val238Glu;Met240Lys]?Het?,E7/CDS7 c.G844 T p.Val282Leu?Hom?,E7/CDS7 c.923₉24insT p.Leu308Phefs*6?Het?,E8/CDS8 c.C955 T p.Gln319Ter?Het?,E8/CDS8 c.C1069 T p.Arg357Trp?Het?,E10/CDS10 c.1451₁452delGGinsC p.Arg484Profs?Het?.MLPA of the proband suggest that there is partial homozygous deletion?ratio=0?,partial duplication and partial normal in exon 3 of CYP21A2 gene,and heterozygous deletion in exon 4 and exon 6-7.Among the family members,7 people were carried gene mutation.The proband showed a non-classical phenotype of final normal height and fertility.Conclusion: All the patients included in this study were adults whose clinical manifestations were not obvious and did not receive timely diagnosis and treatment.By summarizing the characteristics of inheritance,diagnosis and treatment of 21 OHD and 17 OHD in adult patients with CAH,our study provide with many easily overlooked perspectives to the clinicians,and we hope that we can help clinicians to make a early detect and diagnose to non-classical patients with congenital adrenal hyperplasia.Diagnosis and treatment of classical CAH is life-saving,but the diagnosis and treatment of NC-CAH is also important for the prevention of unnecessary pain.Although there is no new mutation were found in our study,it still suggests that the potential phenotype of CAH is related to the residual activity of its allele,and there is a good genotype-phenotype correlation.