Focused Exome Sequencing Gives a High Diagnostic Yield in the Indian Subcontinent.

The genetically isolated yet heterogeneous and highly consanguineous Indian population has shown a higher prevalence of rare genetic disorders. However, there is a significant socioeconomic burden for genetic testing to be accessible to the general population. In the current study, we analyzed next-generation sequencing data generated through focused exome sequencing from individuals with different phenotypic manifestations referred for genetic testing to achieve a molecular diagnosis. Pathogenic or likely pathogenic variants are reported in 280 of 833 cases with a diagnostic yield of 33.6%. Homozygous sequence and copy number variants were found as positive diagnostic findings in 131 cases (15.7%) because of the high consanguinity in the Indian population. No relevant findings related to reported phenotype were identified in 6.2% of the cases. Patients referred for testing due to metabolic disorder and neuromuscular disorder had higher diagnostic yields. Carrier testing of asymptomatic individuals with a family history of the disease, through focused exome sequencing, achieved positive diagnosis in 54 of 118 cases tested. Copy number variants were also found in trans with single-nucleotide variants and mitochondrial variants in a few of the cases. The diagnostic yield and the findings from this study signify that a focused exome test is a good lower-cost alternative for whole-exome and whole-genome sequencing and as a first-tier approach to genetic testing.

Mucopolysaccharidosis Type I Presenting with Persistent Neonatal Respiratory Distress: A Case Report.

Mucopolysaccharidosis type I (MPS I) is a rare inherited autosomal recessive lysosomal storage disorder. Despite several reports on MPS I-related neonatal interstitial lung disease, it is still considered to be an under-recognized disease manifestation. Thus, further study of MPS I is required to improve specific therapies and management strategies. The current report describes a late preterm baby (36 weeks gestational age) with neonatal onset of interstitial lung disease eventually diagnosed as MPS I. The neonate required prolonged respiratory support and oxygen supplementation that further escalated the likely diagnosis of inherited disorders of pulmonary surfactant dysfunction. Whole-exome sequencing confirmed the diagnosis of MPS I, following the observation of low levels of the enzyme α-L-iduronidase. The results highlight the necessity of considering MPS I-related pulmonary involvement in newborns with persistent respiratory insufficiency.