Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare disease with a high mortality rate caused by VPS33B or VIPAS39 mutations. ARC syndrome typically presents with arthrogryposis, renal tubular leak and neonatal cholestatic jaundice, and most patients with this disease do not survive beyond one year.
Here, we report the case of a 13-year-old girl with ARC featuring an incomplete and mild phenotype with novel compound heterozygous mutations of VPS33B. The patient presented with arthrogryposis (claw-shaped limbs), ichthyosis, jaundice, and pruritus. Laboratory tests revealed highly evaluated levels of total bilirubin (TB), direct bilirubin (DB), and total bile acid (TBA) as well as normal levels of gamma-glutamyltransferase (GGT). However, signs of renal dysfunction, as well as other manifestations of ARC syndrome, including nervous system abnormalities, deafness, and failure to thrive, were not observed. The patient\'s clinical symptoms of jaundice and pruritus were significantly alleviated by administration of ursodeoxycholic acid. Whole-exome sequencing (WES) revealed novel compound heterozygous mutations of VPS33B, c.1081 C > T (p.Q361X,257)/c.244 T > C (p.C82R). Both variants were predicted to be pathogenic in silico and have never been reported previously. To date, the patients\' cholestatic jaundice has been well controlled with continuous treatment of ursodeoxycholic acid.
We report the case of a Chinese female with ARC including novel compound heterozygous mutations of VPS33B and an incomplete and mild phenotype. Early diagnosis and suitable symptomatic therapies are critical for the management of ARC patients with mild manifestations and prolonged lifespan.

Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating leukodystrophy with clinical symptoms and imaging manifestations similar to those of Pelizaeus-Merzbacher disease (PMD), an X-linked recessive hypomyelinating leukodystrophy. Typical manifestations of PMLD are nystagmus, dysmyotonia, ataxia, progressive motor dysfunction, and diffuse leukodystrophy on magnetic resonance imaging (MRI). This report identified novel mutations in NCP1 causing PMLD. A 7-month-old male patient was referred to our hospital because he could not lift his head until that time. He had symptoms including congenital nystagmus, hypotonia, and developmental delay. According to the MRI scan, there were signs of leukodystrophy. According to the clinical manifestations and the results of whole-exome sequencing (compound heterozygote mutations in NPC1 (p. G911S, c2731G>A and p. D128H, c382G>C)), the diagnosis of PMLD was considered, and his parents were determined to be carriers of mutant genes. He began rehabilitation training at the age of 1 year old. After 5 years of training, he was still experiencing global developmental delay, equivalent to the developmental level of a nine-month-old child. PMLD is a disease that seriously affects the quality of life of children and can result from mutations in different genes. In this report, we expand the gene spectrum of PMLD and suggest early genetic counselling for suspected patients and their patients.

Progressive familial intrahepatic cholestasis (PFIC) is a group of genetic autosomal recessive disorders that predominantly affects young children and results in early-onset progressive liver damage. Several types of PFIC were defined based on different genetic aetiologies in last decades.
Here, we report a Chinese young child diagnosed as PFIC with variants in tight junction protein 2 (TJP2). The patient was affected by a long history of jaundice, pruritus, and failure to thrive. Highly elevated level of serum total bile acid (TBA) and normal levels of gamma-glutamyltransferase (GGT) were observed at hospitalization. The patient\'s clinical symptoms could be alleviated by administration of ursodeoxycholic acid. Genetic testing by next generation sequencing (NGS) found novel compound heterozygote mutations c.2448 + 1G > C/c.2639delC (p.T880Sfs*12) in TJP2, which were inherited from her mother and father, respectively. Both mutations were predicted to abolish TJP2 protein translation, and neither has previously been identified.
We report a Chinese female PFIC child with novel compound heterozygous mutations of TJP2. Genetic testing by NGS is valuable in the clinical diagnosis of hereditary liver disease.