Clinical genetic analysis of congenital hypothyroidism caused by DUOX2 complex heterozygous variation
Objective To provide genetic consulting and prenatal diagnosis for an 18-week pregnant woman who had previously given birth to a child with congenital hypothyroidism(CH),and to clarify the genetic information and development of the fetus in utero.Clinical genetic analysis of the newly discovered DUOX2 gene complex heterozygous mutation in the progenitor was conducted to improve clinicians'understanding of the disease,so as to better learn about DUOX2 gene muta-tion causing thyroid hormone synthesis disorder causing CH,and improve clinical treatment effect and prognosis of children as much as possible.Methods Peripheral blood of the proband and their parents was extracted to obtain their genomic DNA for whole exome capture and Sanger sequencing,and the results of the obtained biogenetic information were analyzed for pathogenic variation.Amniocentesis was performed on the pregnant woman to extract the fetal DNA of this pregnancy,and the obtained DNA was detected by single-gene PCR.Results The chromosome karyotype of the proband was 46,XX.The proband carried a single leucine deletion in the DUOX2 gene c.3478_3480del(p.Leu1160del)and a complex heterozygous mutation in the DUOX2 gene c.2654G＞T(p.Arg885Leu),which were respectively derived from her father and mother,Paternal c.3478_3480del(p.Leu1160del)was a rare suspected pathogenic mutation,and its functional hazard was predicted to be pos-sibly harmful.The results of amniocentesis suggested that the fetus carried a single leucine heterozygosity deletion of DUOX2 gene paternal c.3478_3480del(p.Leu1160del).Because the DUOX2 gene is an autosomal recessive inheritance pattern,the couple chooses to continue the pregnancy.Conclusion The hybrid mutation of c.3478_3480del(p.Leu1160del)and c.2654G＞T(p.Arg885Leu)is the pathogenic mutation in the proband.All the proband has been normal so far,which suggests the necessity of early diagnosis and treatment.
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