Three children with different de novo BCL11A variants and diverse developmental phenotypes, but shared global motor discoordination and apraxic speech: Evidence for a functional gene network influencing the developing cerebellum and motor and auditory cortices

Laurel Bruce, Beate Peter

Research output: Contribution to journalArticlepeer-review

Abstract

BCL11A is implicated in BCL11A-Related Intellectual Development Disorder (BCL11A-IDD). Previously reported cases had various types of BCL11A variants (copy-number variations [CNVs], singlenucleotide variants [SNVs]). Phenotypes included global, cognitive, and motor delays, autism spectrum disorder (ASD), craniofacial dysmorphology, and speech and language delays described generally, with only two reports specifying childhood apraxia of speech (CAS). Here, we present three additional children with CAS and de novo BCL11A variants, a p.Ala182Thr nonconservative missense and a p.GLu611.Ter nonsense variant, both in exon 4, and a 106 kb deletion harboring exons 1 and 2. All three children have fine and gross motor discoordination, feeding difficulties, and visual motor disorders. Intellectual and learning disabilities and disordered language skills were seen only in the child with the missense variant and the child with the deletion. These findings align with, and expand, previous findings in that BCL11A variants have significant and highly penetrant apraxic effects across motor systems, consistent with cerebellar involvement. The deletion of exons 1 and 2 is the smallest BCL11A CNV with the full phenotypic expression reported to date. The present results support previous findings in that BCL11A-IDD can result from BCL11A variants regardless of type (deletion, SNVs). A gene expression study shows that BCL11 is expressed highly in the early developing cerebellum and primary motor and auditory cortices. Significant co-expression rates in these regions with genes previously implicated in disorders of spoken language and in ASD support the phenotypic overlaps in children with BCL11A-IDD, CAS, and ASD.

Original languageEnglish (US)
JournalAmerican Journal of Medical Genetics, Part A
DOIs
StateAccepted/In press - 2022

Keywords

  • childhood apraxia of speech
  • developmental language disorder
  • functional gene network
  • global motor discoordination
  • variable phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'Three children with different de novo BCL11A variants and diverse developmental phenotypes, but shared global motor discoordination and apraxic speech: Evidence for a functional gene network influencing the developing cerebellum and motor and auditory cortices'. Together they form a unique fingerprint.

Cite this