14q32.11 microdeletion including CALM1, TTC7B, PSMC1, and RPS6KA5: A new potential cause of developmental and language delay in three unrelated patients

Celeste C Eno; Jesper Graakjaer; Dea Svaneby; Mathilde Nizon; Jessica Kianmahd; Rebecca Signer; Julian A Martinez-Agosto; Fabiola Quintero-Rivera

doi:10.1002/ajmg.a.62117

14q32.11 microdeletion including CALM1, TTC7B, PSMC1, and RPS6KA5: A new potential cause of developmental and language delay in three unrelated patients

Am J Med Genet A. 2021 May;185(5):1519-1524. doi: 10.1002/ajmg.a.62117. Epub 2021 Feb 25.

Authors

Celeste C Eno¹, Jesper Graakjaer², Dea Svaneby², Mathilde Nizon³, Jessica Kianmahd⁴, Rebecca Signer⁴, Julian A Martinez-Agosto⁴, Fabiola Quintero-Rivera⁵

Affiliations

¹ Department of Academic Pathology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
² Department of Clinical Genetics, Lillebaelt Hospital, Vejle, Denmark.
³ Department of Medical Genetics, CHU Nantes, Nantes, France.
⁴ Departments of Human Genetics and Pediatrics, Division of Medical Genetics, UCLA, Los Angeles, California, USA.
⁵ Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, California, USA.

PMID: 33634591
DOI: 10.1002/ajmg.a.62117

Abstract

Three unrelated patients with similar microdeletions of chromosome 14q32.11 with shared phenotypes including language and developmental delay, and four overlapping genes -CALM1, TTC7B, PSMC1, and RPS6KA5 have been presented. All four genes are expressed in the brain and have haploinsufficiency scores, which reflect low tolerance to loss of function variation. An insight on the genes in the overlapping region, which may influence the resulting phenotype has been provided. Given the three patients' similar phenotypes and lack of normal variation in this region, it was suggested that this microdeletion may be associated with developmental and language delay.

Keywords: CALM1; PSMC1; RPS6KA5; TTC7B; developmental delay; microdeletion 14q32.11.

Publication types

Case Reports

MeSH terms

ATPases Associated with Diverse Cellular Activities / genetics*
Calmodulin / genetics*
Child
Child, Preschool
Chromosome Deletion
Chromosomes, Human, Pair 14 / genetics
Comparative Genomic Hybridization / methods
Haploinsufficiency / genetics
Humans
Language Development Disorders / genetics*
Language Development Disorders / pathology
Male
Pedigree
Phenotype
Proteins / genetics*
Ribosomal Protein S6 Kinases, 90-kDa / genetics*

Substances

CALM1 protein, human
Calmodulin
Proteins
TTC7A protein, human
Ribosomal Protein S6 Kinases, 90-kDa
mitogen and stress-activated protein kinase 1
ATPases Associated with Diverse Cellular Activities
PSMC1 protein, human