Dataset Information

Detection of chromosomal breakpoints in patients with developmental delay and speech disorders.

ABSTRACT: Delineating candidate genes at the chromosomal breakpoint regions in the apparently balanced chromosome rearrangements (ABCR) has been shown to be more effective with the emergence of next-generation sequencing (NGS) technologies. We employed a large-insert (7-11 kb) paired-end tag sequencing technology (DNA-PET) to systematically analyze genome of four patients harbouring cytogenetically defined ABCR with neurodevelopmental symptoms, including developmental delay (DD) and speech disorders. We characterized structural variants (SVs) specific to each individual, including those matching the chromosomal breakpoints. Refinement of these regions by Sanger sequencing resulted in the identification of five disrupted genes in three individuals: guanine nucleotide binding protein, q polypeptide (GNAQ), RNA-binding protein, fox-1 homolog (RBFOX3), unc-5 homolog D (C.elegans) (UNC5D), transmembrane protein 47 (TMEM47), and X-linked inhibitor of apoptosis (XIAP). Among them, XIAP is the causative gene for the immunodeficiency phenotype seen in the patient. The remaining genes displayed specific expression in the fetal brain and have known biologically relevant functions in brain development, suggesting putative candidate genes for neurodevelopmental phenotypes. This study demonstrates the application of NGS technologies in mapping individual gene disruptions in ABCR as a resource for deciphering candidate genes in human neurodevelopmental disorders (NDDs).

SUBMITTER: Utami KH

PROVIDER: S-EPMC3946304 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Detection of chromosomal breakpoints in patients with developmental delay and speech disorders.

Utami Kagistia H KH Hillmer Axel M AM Aksoy Irene I Chew Elaine G Y EG Teo Audrey S M AS Zhang Zhenshui Z Lee Charlie W H CW Chen Pauline J PJ Seng Chan Chee CC Ariyaratne Pramila N PN Rouam Sigrid L SL Soo Lim Seong LS Yousoof Saira S Prokudin Ivan I Peters Gregory G Collins Felicity F Wilson Meredith M Kakakios Alyson A Haddad Georges G Menuet Arnaud A Perche Olivier O Tay Stacey Kiat Hong SK Sung Ken W K KW Ruan Xiaoan X Ruan Yijun Y Liu Edison T ET Briault Sylvain S Jamieson Robyn V RV Davila Sonia S Cacheux Valere V

PloS one 20140306 6

Delineating candidate genes at the chromosomal breakpoint regions in the apparently balanced chromosome rearrangements (ABCR) has been shown to be more effective with the emergence of next-generation sequencing (NGS) technologies. We employed a large-insert (7-11 kb) paired-end tag sequencing technology (DNA-PET) to systematically analyze genome of four patients harbouring cytogenetically defined ABCR with neurodevelopmental symptoms, including developmental delay (DD) and speech disorders. We c ...[more]

PMID: 24603971

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Project description:The goal of this research was to obtain initial estimates of the prevalence of each of four types of motor speech disorders in children with idiopathic Speech Delay (SD) and to use findings to estimate the population-based prevalence of each disorder. Analyses were completed on audio-recorded conversational speech samples from 415 children recruited for research in idiopathic SD in six USA cities during the past three decades. The speech and motor speech status of each participant was cross-classified using standardized measures in the finalized version of the Speech Disorders Classification System described in the Supplement. Population-based prevalence estimates for the four motor speech disorders were calculated from epidemiological studies of SD conducted in Australia, England, and the USA. A total of 82.2% of the 415 participants with SD met criteria for No Motor Speech Disorder at assessment, 12% met criteria for Speech Motor Delay, 3.4% met criteria for Childhood Dysarthria, 2.4% met criteria for Childhood Apraxia of Speech, and 0% met criteria for concurrent Childhood Dysarthria and Childhood Apraxia of Speech. The estimated population-based prevalence of each of the first three motor speech disorders at 4 to 8 years of age were Speech Motor Delay: 4 children per 1,000; Childhood Dysarthria: 1 child per 1,000; and Childhood Apraxia of Speech: 1 child per 1,000. The latter finding cross-validates a prior prevalence estimate for Childhood Apraxia of Speech of 1-2 children per 1,000. Findings are interpreted to indicate a substantial prevalence of motor speech disorders in children with idiopathic SD. Abbreviations: CAS, childhood apraxia of speech; CD, childhood dysarthria; CND, complex neurodevelopmental disorders; DI, dysarthria index; DSI, dysarthria subtype indices; MSD, motor speech disorder; No MSD, no motor speech disorder; NSA, normal(ized) speech acquisition; PEPPER, programs to examine phonetic and phonologic evaluation records; PM, pause marker; PMI, pause marker index; PSD, persistent speech delay; PSE, persistent speech errors; SD, speech delay; SDCS, speech disorders classification system; SDCSS, speech disorders classification system summary; SE, speech errors; SMD, speech motor delay.

Dataset Information

Detection of chromosomal breakpoints in patients with developmental delay and speech disorders.

Publications

Detection of chromosomal breakpoints in patients with developmental delay and speech disorders.

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