Mutations associated with Arthrogryposis, Renal Dysfunction, and Cholestasis in two patients Archana Rai, Meenakshi Lallar, SR Phadke Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow-226014, India *Contact: arai8967@gmail.com
Representative Cases
Abstract Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is a rare autosomal recessive disorder caused by defects in the VPS33B and VIPAS39 genes. This study was done to look for mutations associated with Arthrogryposis, Renal Dysfunctionn and Cholestasis in two patients. For this, Exome sequencing was done in both the patients and data was analysed. It revealed two novel mutations in both of them. Making the definite diagnosis of the syndrome is important as it can provide the prenatal diagnosis for this severe and lethal disorder with no treatment.
C A S E 1
Introduction Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome (OMIM 208085, 613404) is a rare autosomal recessive disorder caused by defects in the VPS33B and VIPAS39 and VPS33B mutations are detectable in approximately 75% of patients
C A S E 2
Pedigree of 2 cases
Family 1
Results
Family 2
Summary of mutation proven patients Family
VPS33B; c.558_559delCT (Y187Wfs*18)
VIPAS39; c.618_626dup3
Age of Patient
Clinical Presentation
Exome Sequencing Result (IGV)
Family 1 3 months Jaundice and pale stools since birth. yellowish discoloration of skin and urine since day 3 of life, failure to gain weight, dry skin, abnormalities in posture of hands and feet, loose dry and scaly skin, scanty subcutaneous fat, menace reflex, contracture at proximal interphalangeal joint, upslanting eyes, varus deformity of hands, fixed dorsiflexion at bilateral ankle joint
Proband
Sanger Sequencing Validation
Proband
Parents
Family 2 7 days
Yellowish skin discoloration, dark yellow urine, acholic stools and failure to thrive, renal tubular acidosis, micrognathia and arthrogryposis of bilateral knees, failure to gain weight
Objective To look for mutations associated with Arthrogryposis, Renal Dysfunctionn and Cholestasis in two patients
Study Subjects
Exome Sequencing
Analysis
Management and Prognosis No specific treatment currently exists for ARC syndrome and prognosis is poor. Risk of recurrence is 25%.
Conclusion
Material and Methods Collection of blood and isolation of DNA
Case 2
Case 1
Sanger Validation
We identified two novel mutations in two patients from two different families Making the definite diagnosis of the syndrome is important as it can provide the prenatal diagnosis for this severe and lethal disorder with no treatment Acknowledgement : Department of Biotechnology for funding and fellowship