Identification of genetic variants associated with a wide spectrum of phenotypes clinically diagnosed as Sanfilippo and Morquio syndromes using whole genome sequencing

Mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders (LSDs). MPSs caused by excessive accumulation of mucopolysaccharides due to missing or deficiency enzymes required for the degradation specific macromolecules. MPS I-IV, VI, VII, and IX sub-types mucopolysaccharidoses. Among these, III (also known as Sanfilippo) IV (Morquio) syndromes lethal prevalent sub-types. This study aimed identify causal genetic variants in cases characterize genotype-phenotype relations Pakistan. We performed clinical, biochemical analysis using Whole Genome Sequencing (WGS) 14 Pakistani families affected with IV. Patients were classified into history aggressive behaviors, dementia, clear cornea short trunk, stature, reversed ratio upper segment lower a segment. Data variant selections made based on segregation analysis, examination genes, gene function, expression, pathogenicity ACMG guidelines silico analysis. In total, 58 individuals from included present study. Six clinically diagnosed eight WGS revealed MPS-associated genes including NAGLU, SGSH, GALNS, GNPTG well VWA3B , BTD which have not previously associated MPS. One family had both GALNS . Accurate early diagnosis children represents helpful step designing therapeutic strategies protect different organs permanent damage. addition, pre-natal screening identification etiology will facilitate counselling families. Identification novel might help identifying new targeted therapies treat LSDs.