关键词: Rahman综合征；　HIST1H1E基因；　组蛋白H1；　基因突变

Abstract: Objective　To analyze the clinical manifestations and genetic change of Rahman syndrome caused by HIST1H1E gene. Methods　Clinical data of a patient with Rahman syndrome caused by HIST1H1E gene mutation in our hospital in October 2018 were retrospectively analyzed the and the related literature retrieved using "Rahman syndrome", "HIST1H1E gene", "histone H1"and "mutation" as the key words, in Chinese Knowledge Databases, Wanfang Data, Wiper Databases and PUBMED database before December 2019 were reviewed. Results　A boy aged 2 years and 8 months old came to our hospital because of developmental retardation for more than 2 years. Physical examination found increased weight and large head circumference, high hairline, full cheeks, telecanthus, short palpebral fissures, scrotum without palpable testicles, but with firm mass in inguinal regions. Blood Amino acid and carnitine spectrum test showed a increase of hydroxyl isovalerate carnitine and acetyl carnitine, combining with a decrease of ornithine. Scrotum ultrasound revealed bilateral testis tissue in inguinal region. Bone age is consistent with the age of five and a half years. Echocardiographic and pituitary MRI showed normal. Child Developmental Screening Test with DQ<50 and MI <48.Whole exome sequencing identified a heterozygous mutation of c.446dupA (p.Ser150Glufs*46) on HIST1H1E gene. It's the first case with Rahman syndrome reported in china and this variant has not been reported in the Human Gene Mutation Database (HGMD) and gnomAD. Meanwhile this is a de novo frameshift mutation classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG). There are 31 cases (13 males and 18 females) with HIST1H1E gene mutation founded in four English publications. Fourteen mutations were included, all of which were frameshift mutation located in the 94 base pair region of C-terminal domain in HIST1H1E gene, which resulted in the formation of the same mutant protein with a 38-amino-acid tail. Conclusion　Rahman syndrome is a rare autosomal dominant hereditary disease caused by HIST1H1E gene mutation, which is characterized by similar facial dysmorphism, combining with varied body overgrowth and intellectual disability. Whole exome sequencing may be helpful for early diagnosis.

Key words: 　Rahman syndrome;　HIST1H1E gene;　Histone H1;　Mutation;