Dataset Information

Exome sequencing identifies novel and known mutations in families with intellectual disability.

ABSTRACT:

Background

Intellectual disability (ID) is a phenotypically and genetically heterogeneous disorder.

Methods

In this study, genome wide SNP microarray and whole exome sequencing are used for the variant identification in eight Pakistani families with ID. Beside ID, most of the affected individuals had speech delay, facial dysmorphism and impaired cognitive abilities. Repetitive behavior was observed in MRID143, while seizures were reported in affected individuals belonging to MRID137 and MRID175.

Results

In two families (MRID137b and MRID175), we identified variants in the genes CCS and ELFN1, which have not previously been reported to cause ID. In four families, variants were identified in ARX, C5orf42, GNE and METTL4. A copy number variation (CNV) was identified in IL1RAPL1 gene in MRID165.

Conclusion

These findings expand the existing knowledge of variants and genes implicated in autosomal recessive and X linked ID.

SUBMITTER: Rasheed M

PROVIDER: S-EPMC8399827 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exome sequencing identifies novel and known mutations in families with intellectual disability.

Rasheed Memoona M Khan Valeed V Harripaul Ricardo R Siddiqui Maimoona M Malik Madiha Amin MA Ullah Zahid Z Zahid Muhammad M Vincent John B JB Ansar Muhammad M

BMC medical genomics 20210827 1

<h4>Background</h4>Intellectual disability (ID) is a phenotypically and genetically heterogeneous disorder.<h4>Methods</h4>In this study, genome wide SNP microarray and whole exome sequencing are used for the variant identification in eight Pakistani families with ID. Beside ID, most of the affected individuals had speech delay, facial dysmorphism and impaired cognitive abilities. Repetitive behavior was observed in MRID143, while seizures were reported in affected individuals belonging to MRID1 ...[more]

PMID: 34452636

Similar Datasets

Project description:BACKGROUND: X-linked intellectual disability (XLID) is a group of genetically heterogeneous disorders characterized by substantial impairment in cognitive abilities, social and behavioral adaptive skills. Next generation sequencing technologies have become a powerful approach for identifying molecular gene mutations relevant for diagnosis. METHODS & OBJECTIVES: Enrichment of X-chromosome specific exons and massively parallel sequencing was performed for identifying the causative mutations in 14 Finnish families, each of them having several males affected with intellectual disability of unknown cause. RESULTS: We found four novel mutations in known XLID genes. Two mutations; one previously reported missense mutation (c.1111C > T), and one novel frameshift mutation (c. 990_991insGCTGC) were identified in SLC16A2, a gene that has been linked to Allan-Herndon-Dudley syndrome (AHDS). One novel missense mutation (c.1888G?>?C) was found in GRIA3 and two novel splice donor site mutations (c.357 + 1G > C and c.985 + 1G > C) were identified in the DLG3 gene. One missense mutation (c.1321C > T) was identified in the candidate gene ZMYM3 in three affected males with a previously unrecognized syndrome characterized by unique facial features, aortic stenosis and hypospadia was detected. All of the identified mutations segregated in the corresponding families and were absent in > 100 Finnish controls and in the publicly available databases. In addition, a previously reported benign variant (c.877G > A) in SYP was identified in a large family with nine affected males in three generations, who have a syndromic phenotype. CONCLUSIONS: All of the mutations found in this study are being reported for the first time in Finnish families with several affected male patients whose etiological diagnoses have remained unknown to us, in some families, for more than 30 years. This study illustrates the impact of X-exome sequencing to identify rare gene mutations and the challenges of interpreting the results. Further functional studies are required to confirm the cause of the syndromic phenotypes associated with ZMYM3 and SYP in this study.

Dataset Information

Exome sequencing identifies novel and known mutations in families with intellectual disability.

Background

Methods

Results

Conclusion

Publications

Exome sequencing identifies novel and known mutations in families with intellectual disability.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets