TY - JOUR
T1 - Next-Generation Sequencing Reveals Novel Mutations in X-linked Intellectual Disability
AU - Muthusamy, Babylakshmi
AU - Selvan, Lakshmi Dhevi N.
AU - Nguyen, Thong T.
AU - Manoj, Jesna
AU - Stawiski, Eric W.
AU - Jaiswal, Bijay S.
AU - Wang, Weiru
AU - Raja, Remya
AU - Ramprasad, Vedam Laxmi
AU - Gupta, Ravi
AU - Murugan, Sakthivel
AU - Kadandale, Jayarama S.
AU - Keshava Prasad, T. S.
AU - Reddy, Kavita
AU - Peterson, Andrew
AU - Pandey, Akhilesh
AU - Seshagiri, Somasekar
AU - Girimaji, Satish Chandra
AU - Gowda, Harsha
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Robust diagnostics for many human genetic disorders are much needed in the pursuit of global personalized medicine. Next-generation sequencing now offers new promise for biomarker and diagnostic discovery, in developed as well as resource-limited countries. In this broader global health context, X-linked intellectual disability (XLID) is an inherited genetic disorder that is associated with a range of phenotypes impacting societies in both developed and developing countries. Although intellectual disability arises due to diverse causes, a substantial proportion is caused by genomic alterations. Studies have identified causal XLID genomic alterations in more than 100 protein-coding genes located on the X-chromosome. However, the causes for a substantial number of intellectual disability and associated phenotypes still remain unknown. Identification of causative genes and novel mutations will help in early diagnosis as well as genetic counseling of families. Advent of next-generation sequencing methods has accelerated the discovery of new genes involved in mental health disorders. In this study, we analyzed the exomes of three families from India with nonsyndromic XLID comprising seven affected individuals. The affected individuals had varying degrees of intellectual disability, microcephaly, and delayed motor and language milestones. We identified potential causal variants in three XLID genes, including PAK3 (V294M), CASK (complex structural variant), and MECP2 (P354T). Our findings reported in this study extend the spectrum of mutations and phenotypes associated with XLID, and calls for further studies of intellectual disability and mental health disorders with use of next-generation sequencing technologies.
AB - Robust diagnostics for many human genetic disorders are much needed in the pursuit of global personalized medicine. Next-generation sequencing now offers new promise for biomarker and diagnostic discovery, in developed as well as resource-limited countries. In this broader global health context, X-linked intellectual disability (XLID) is an inherited genetic disorder that is associated with a range of phenotypes impacting societies in both developed and developing countries. Although intellectual disability arises due to diverse causes, a substantial proportion is caused by genomic alterations. Studies have identified causal XLID genomic alterations in more than 100 protein-coding genes located on the X-chromosome. However, the causes for a substantial number of intellectual disability and associated phenotypes still remain unknown. Identification of causative genes and novel mutations will help in early diagnosis as well as genetic counseling of families. Advent of next-generation sequencing methods has accelerated the discovery of new genes involved in mental health disorders. In this study, we analyzed the exomes of three families from India with nonsyndromic XLID comprising seven affected individuals. The affected individuals had varying degrees of intellectual disability, microcephaly, and delayed motor and language milestones. We identified potential causal variants in three XLID genes, including PAK3 (V294M), CASK (complex structural variant), and MECP2 (P354T). Our findings reported in this study extend the spectrum of mutations and phenotypes associated with XLID, and calls for further studies of intellectual disability and mental health disorders with use of next-generation sequencing technologies.
KW - Diagnostic medicine
KW - genotype-phenotype association
KW - mental retardation
KW - neurodevelopmental disorders
KW - next-generation sequencing
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U2 - 10.1089/omi.2017.0009
DO - 10.1089/omi.2017.0009
M3 - Article
C2 - 28481730
AN - SCOPUS:85019068138
SN - 1536-2310
VL - 21
SP - 295
EP - 303
JO - OMICS A Journal of Integrative Biology
JF - OMICS A Journal of Integrative Biology
IS - 5
ER -