Two novel mutations in the VPS33B gene in a Chinese patient with arthrogryposis,renal dysfunction and cholestasis syndrome 1:A case report

BACKGROUND The VPS33B(OMIM:608552)gene is located on chromosome 15q26.1.We found a female infant with autosomal recessive arthrogryposis,renal dysfunction and cholestasis syndrome 1(ARCS1)caused by mutation in VPS33B.The child was diagnosed with ARCS1(OMIM:208085)after the whole exome sequencing revealed two heterozygous mutations(c.96+1G>C,c.242delT)in the VPS33B gene.CASE SUMMARY We report a Chinese female infant with neonatal cholestasis disorder,who was eventually diagnosed with ARCS1 by genetic analysis.Genetic testing revealed two new mutations(c.96+1G>C and c.242delT)in VPS33B,which is the causal gene.The patient was compound heterozygous,and her parents were both heterozygous.CONCLUSION This study extends the mutational spectrum of the VPS33B gene to provide a molecular basis for the etiological diagnosis of ARCS1 and for genetic counseling of the family.

Clinical manifestations and gene analysis of Hutchinson-Gilford progeria syndrome:A case report

BACKGROUND This case report describes a child with Hutchinson-Gilford progeria syndrome(HGPS,OMIM:176670)caused by LMNA(OMIM:150330)gene mutation,and we have previously analyzed the clinical manifestations and imaging characteristics of this case.After 1-year treatment and follow-up,we focus on analyzing the changes in the clinical manifestations and genetic diagnosis of the patient.CASE SUMMARY In April 2020,a 2-year-old boy with HGPS was found to have an abnormal appearance,and growth and development lagged behind those of children of the same age.The child’s weight did not increase normally,the veins of the head were clearly visible,and he had shallow skin color and sparse yellow hair.Peripheral blood DNA samples obtained from the patient and his parents were sequenced using high-throughput whole-exosome sequencing,which was verified by Sanger sequencing.The results showed that there was a synonymous heterozygous mutation of C.1824 C>T(P.G608G)in the LMNA gene.CONCLUSION Mutation of the LMNA gene provides a molecular basis for diagnosis of HGPS and genetic counseling of the family.

Novel compound heterozygous variants in the LHX3 gene caused combined pituitary hormone deficiency: A case report

BACKGROUND Combined pituitary hormone deficiency 3(CPHD3;OMIM:221750)is caused by mutations within the LHX3 gene(OMIM:600577),which located on the subtelomeric region of chromosome 9 at band 9q34.3,has seven coding exons and six introns.LIM homeobox(LHX)3 protein is the key regulator of pituitary development in fetal life.CASE SUMMARY We have diagnosed and treate an 11-year-old boy with combined pituitary hormone deficiency(CPHD).The main clinical manifestations were pituitary hormone deficiency,hydrocele of the tunica vaginalis,pituitary dwarfism,gonadal dysplasia,micropenis,clonic convulsion,and mild facial dysmorphic features.We collected peripheral blood from the patient,the patient's older brother,as well as their parents,and sequenced them by using high-throughput whole-exosome sequencing,which was verified by Sanger sequencing.The results showed that there were two compound heterozygous variants of c.613G>C(p.V205L)and c.220T>C(p.C74R)in the LHX3 gene.c.613G>C(p.V205L)was inherited from his mother and c.220T>C(p.C74R)from his father.His brother also has both variants and symptoms.CONCLUSION This study reported ununreported genetic mutations of LHX3,and recorded the treatment process of the patients,providing data for the diagnosis and treatment of CPHD.