10.1371/journal.pone.0093409PLoS ONE94-POLN

A Kakita

AI Alvarez Retuerto

Angeline Lai

B Devlin

B Meder

BJ O'Roak

BM Neale

BP Coe

Breana Cham

C Betancur

CS Leblond

D Horn

Ee-Shien Tan

Ene-Choo Tan

FF Hamdan

Hao Sun

HY Kroes

Ivy Ng

J Chelly

John McPherson

JR Lemke

K Neveling

LA Jolly

Lai-Choo Ong

M Pantaleon

M Rehnberg

Maggie Brett

MH Jones

MT Carter

N Matsunami

OS Latiff ZA

Patrick Tan

PS Tarpey

R Gibbons

R Sultana

RJ Ferland

RJ Gibbons

S Dupont

S Girirajan

S Kunishima

SJ Sanders

Steve Rozen

U Finckh

VM Kalscheuer

Z Brownstein

Zhi Jiang Zang

PLoS ONE

PubMed

Brett Maggie

McPherson John

Zang Zhi Jiang

Lai Angeline

Tan Ee-Shien

Ng Ivy

Ong Lai-Choo

Cham Breana

Tan Patrick

Rozen Steve

Tan Ene-Choo

Public Library of Science (PLOS)

Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

Crossref

Developmental delay and/or intellectual disability (DD/ID) affects 1-3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81-84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism

Brett, Maggie

McPherson, John

Zang, Zhi Jiang

Lai, Angeline

Tan, Ee-Shien

Ng, Ivy

Ong, Lai-Choo

Cham, Breana

Tan, Patrick

Rozen, Steve

Tan, Ene-Choo

eScholarship - University of California

English

<div><p>Developmental delay and/or intellectual disability (DD/ID) affects 1–3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81–84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the <i>ATRX</i> gene and a canonical splice site mutation in the <i>L1CAM</i> gene. In a third patient, a canonical splice site variant in the <i>USP9X</i> gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism.</p></div

Maggie Brett (545719)

John McPherson (545720)

Zhi Jiang Zang (545721)

Angeline Lai (545722)

Ee-Shien Tan (545723)

Ivy Ng (89844)

Lai-Choo Ong (545724)

Breana Cham (545725)

Patrick Tan (18147)

Steve Rozen (134498)

Ene-Choo Tan (545726)

The Francis Crick Institute

Directory of Open Access Journals

Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel.

http://dx.doi.org/10.1371/journal.pone.0093409

Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel

Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel

Abstract

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Public Library of Science (PLOS)

Crossref

Public Library of Science (PLOS)

eScholarship - University of California

The Francis Crick Institute

Directory of Open Access Journals