# Genetic Investigation of Minimally Verbal Children with ASD

> **NIH NIH P50** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2020 · $448,522

## Abstract

PROJECT SUMMARY/ ABSTRACT
Autism Spectrum Disorder (ASD) is highly heterogeneous in its clinical presentation, which complicates
diagnosis, prognosis and treatment. As the genetic basis for ASD becomes increasingly understood, we are
challenged to understand how genetic risk translates to specific phenotypes, trajectories and mechanisms. The
deep phenotyping and treatment of children who are minimally verbal (MV) provides a unique opportunity to
identify potential genetic risk factors or predictors, which is the major aim of this genetics project. Moreover,
the addition of the MV ASD cohort to the broader collection of autism families available for molecular study will
enhance our understanding of the genetic heterogeneity underlying ASD as a whole. This project will be
undertaken by Daniel Geschwind, MD, PhD, and his colleagues at UCLA. We hypothesize that subgroups of
MV children may represent genetically more-homogeneous cohorts of ASD with characteristic genetic profiles.
Specific syndromes associated with ASD have specific behavioral and cognitive profiles, including language
phenotypes (Barnett and van Bon, 2015; D'Angelo et al., 2016; DiStefano et al., 2016; Niklasson et al., 2009;
Penagarikano and Geschwind, 2012; van Bon et al., 2010). Further, rare, large effect size de novo mutations
are more likely to be associated with more severe phenotypes, including low IQ and severe language
impairment (Geschwind and Konopka, 2009; Robinson et al., 2014; Sanders et al., 2015). Genetic testing
using microarrays and whole-exome sequencing (WES) is clinically indicated in the evaluation of ASD to
identify large effect pathogenic copy number variants (CNV) and de novo protein disrupting mutations (Jeste
and Geschwind, 2014; Miller et al., 2010; Schaefer et al., 2008). Given that the prevalence of CNV is
associated with severity, e.g., those with low IQ and language impairment may have a frequency of CNV as
high as 25% (Jacquemont et al., 2006) and the yield of WES is likely 10-20%, we will use SNP microarrays to
identify likely causal CNVs and WES, thereby providing a “molecular diagnosis” for a subset of patients. We
will evaluate the correlation between ASD liability due to common genetic variation genome-wide and
quantitative measures of oromotor and auditory functioning (Projects 1 and 2); speech and language ability
(Core B); and response to intervention (Project 3). We hypothesize that genetic profile may correlate with
response to language intervention (Project 3), with the future goal of taking a first step toward generating
predictors that may be useful to prospectively place children into the most appropriate interventions.

## Key facts

- **NIH application ID:** 10001019
- **Project number:** 5P50DC018006-02
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** DANIEL H GESCHWIND
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,522
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001019

## Citation

> US National Institutes of Health, RePORTER application 10001019, Genetic Investigation of Minimally Verbal Children with ASD (5P50DC018006-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10001019. Licensed CC0.

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