Analysis Of Clinical And Genetics In 5 Children With Kallmann Syndrome

Objective:To analysis the genotype and clinical phenotypes of 5 children with Kallmann syndrome(KS)and review literatures.Methods:1.From July 2015 to July 2017,the clinical data of KS children in Department of Pediatrics of the First Affiliated Hospital of Zhejiang University Medical College were collected.2.DNA from peripheral blood samples of 5 children with KS and their parents were extracted,and sequenced by high-throughput sequencing.The positive mutation was verified by Sanger sequencing,and Polyphen2 and SIFT were used to predict the mutation function.3.Up to August 2017,the key words,including "Kallmann syndrome","idiopathic hypogonadotropic hypogonadism" and "Kallmann syndrome and China",were reviewed using the following search engines:China CNKI,Wanfang database,VIP database and PubMed database.Results:1.During the past-2 years,a total of 5 children with KS were diagnosed,aged from 6-month-old to 19-year-old,including 4 males and 1 female.Hypogonadotropic hypogonadism was manifested in all patients;3 cases had olfactory function defects;2 cases had olfactory bulb dysplasia on MRI;1 case presented with cleft lip and palate;in case 4,the infant showed small penis and cryptorchidism with right renal agenesis.Chromosome karyotype were normal and their parents were asymptomatic in all cases;the proband's uncle in case 5 has secondary sexual insufficiency with olfactory disorder.2.The mutation[c.1877 1887del(p.S627Tfs*6)]of KALI genes was found in the case 4,and the same mutation was detected in his mother.The heterozygous variation{c.1097C>T[p.(Pro366Leu)]and c.809G>C(p.G270A)} of FGFR1 gene was found in case 3 and 5,respectively,and the same mutation was detected in their father.3.Literature search found that Chinese KS pathogenic gene mutation coverage is not high(about 22.7%),of which the first three are KALI(43.7%),FGFR1(26.4%),PROKR2(19.5%).And a mutation of c.1877 1887/p.S627Tfs*6 in KAL1 has not been reported.Conclusions:In China,KALI,FGFR1 and PROKR2 are the main causative genes for Kallmann syndrome in children,and a novel mutation was found in 5 children with Kallmann syndrome.Early gene detection of suspected cases is helpful for early diagnosis.