ESPE Abstracts

Objectives: To present Chung-Jansen Syndrome or CHUJANS by a de novo variant in the pleckstrin homology domain-interacting protein (PHIP) gene and compare the clinical phenotype with previous case reports; ②To provide a novel genetic detection methods with whole-exome sequencing(WES) and whole genome sequencing(WGS) and Sanger sequencing for rare genetic diseases.

Patients and methods: Following collecting clinical datas of individual and studing systematic reviews, we compare our case with previous reports from variant types and phenotype.In addition to WES to find out the variant site, we add WGS to determine and Sanger sequencing to confirm it.

Results: A 11-year-old male borned with normal vaginal delivery at full term with weighted 3.2kg, measured 50 cm, had delayed in motor and language development since childhood like walking alone and calling "father and mother" after 3-year-old. He gained fast weight 4 years old(5kg/kg) which led him to obesity with BMI 29.76kg/m2(>97th percentile). He had poor academic performances and social skills. The examination revealed dysmorphic features like large ears with thick helices and earlobes, full eyebrows, uptured nose, thick nasal alar, slight purple lines in bilateral groins, occult penis. Investigations showed that increased serum AST 69U/l, ALT 118U/l, TG 2.74mmol/l, CHOL 7.46mmol/l, LDL-C 4.91mmol/l, UA 484 μmol/l, decreased serum HDL-C 1.16mmol/L. No abnormalities were found in blood electrolytes, kidney function, thyroid function, cortisol, ACTH, sex hormone and glucose metabolism. Bone age was 11 years and 6 months. Urinary and testicular color doppler ultrasound, heart color doppler ultrasound, the MRI brain and pituitary were normal; Evaluation of intelligence showed intellectual disability; Chromosome karyotype was 46, XY and WES revealed a de novo variant in PHIP Gene in Exon16-19 (NM_017934.6: c.79707131-79713575 del). According to previous reports, there were 35 individuals having unique variants from 37 cases, including missense, nonvariant, frameshift, translocation, splice and multiple gene delete, while two groups of individuals were identified to have similar clinical phenotypes with same variant sites.

Conclusion: The loss-of-function mutation(LOF) in PHIP gene can lead to Chung-Jansen Syndrome, which is a rare chromosomal dominant genetic disorder, characterized by global developmental delay, intellectual disability, obesity, behavioral problems, dysmorphic features. Despite a large fragment deletion as a novel variant, our individual displays similar clinical phenotype comparing with those previously. Therefore, Chung-Jansen Syndrome should be considered with an obese children as well as developmental delay, intellectual disability, behavioral problems, dysmorphic features. Genetic detection methods is beneficial for definitive diagnosis.