Expanding the clinical spectrum associated with PACS2 mutations

Research output: Contribution to journalArticle

Abstract

Whole exome sequencing (WES) has led to the understanding of the molecular events affecting neurodevelopment in an extremely diverse clinical context, including diseases with intellectual disability (ID) associated with variable central nervous system (CNS) malformations, and developmental and epileptic encephalopathies (DEEs). Recently, PACS2 mutations have been causally linked to a DEE with cerebellar dysgenesis and facial dysmorphism. All known patients presented with a recurrent de novo missense mutation, c.625G>A (p.Glu209Lys). Here, we report on a 7-year-old boy with DEE, cerebellar dysgenesis, facial dysmorphism and postnatal growth delay, apparently not fitting with any recognized disorder. WES disclosed a de novo novel missense PACS2 variant, c.631G>A (p.Glu211Lys), as the molecular cause of this complex phenotype. We provide a detailed clinical characterization of this patient, and analyse the available clinical data of individuals with PACS2 mutations to delineate more accurately the clinical spectrum associated with this recently described syndrome. Our study expands the clinical and molecular spectrum of PACS2 mutations. Overview of the available clinical data allow to delineate the condition associated with PACS2 mutations as a variable trait, in which the key features are represented by moderate to severe ID, cerebellar dysgenesis and other CNS malformations, reduced growth, and facial dysmorphism.

Original languageEnglish
Pages (from-to)525-531
Number of pages7
JournalClinical Genetics
Volume95
Issue number4
DOIs
Publication statusPublished - Apr 2019

Fingerprint

Brain Diseases
Nervous System Malformations
Exome
Mutation
Intellectual Disability
Central Nervous System
Missense Mutation
Growth
Phenotype

Cite this

@article{31484bcb134e43f18a527f4d75d1e05f,
title = "Expanding the clinical spectrum associated with PACS2 mutations",
abstract = "Whole exome sequencing (WES) has led to the understanding of the molecular events affecting neurodevelopment in an extremely diverse clinical context, including diseases with intellectual disability (ID) associated with variable central nervous system (CNS) malformations, and developmental and epileptic encephalopathies (DEEs). Recently, PACS2 mutations have been causally linked to a DEE with cerebellar dysgenesis and facial dysmorphism. All known patients presented with a recurrent de novo missense mutation, c.625G>A (p.Glu209Lys). Here, we report on a 7-year-old boy with DEE, cerebellar dysgenesis, facial dysmorphism and postnatal growth delay, apparently not fitting with any recognized disorder. WES disclosed a de novo novel missense PACS2 variant, c.631G>A (p.Glu211Lys), as the molecular cause of this complex phenotype. We provide a detailed clinical characterization of this patient, and analyse the available clinical data of individuals with PACS2 mutations to delineate more accurately the clinical spectrum associated with this recently described syndrome. Our study expands the clinical and molecular spectrum of PACS2 mutations. Overview of the available clinical data allow to delineate the condition associated with PACS2 mutations as a variable trait, in which the key features are represented by moderate to severe ID, cerebellar dysgenesis and other CNS malformations, reduced growth, and facial dysmorphism.",
author = "Dentici, {Maria L} and Sabina Barresi and Marcello Niceta and Andrea Ciolfi and Marina Trivisano and Andrea Bartuli and Digilio, {Maria C} and Nicola Specchio and Bruno Dallapiccola and Marco Tartaglia",
note = "{\circledC} 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2019",
month = "4",
doi = "10.1111/cge.13516",
language = "English",
volume = "95",
pages = "525--531",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "4",

}

TY - JOUR

T1 - Expanding the clinical spectrum associated with PACS2 mutations

AU - Dentici, Maria L

AU - Barresi, Sabina

AU - Niceta, Marcello

AU - Ciolfi, Andrea

AU - Trivisano, Marina

AU - Bartuli, Andrea

AU - Digilio, Maria C

AU - Specchio, Nicola

AU - Dallapiccola, Bruno

AU - Tartaglia, Marco

N1 - © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2019/4

Y1 - 2019/4

N2 - Whole exome sequencing (WES) has led to the understanding of the molecular events affecting neurodevelopment in an extremely diverse clinical context, including diseases with intellectual disability (ID) associated with variable central nervous system (CNS) malformations, and developmental and epileptic encephalopathies (DEEs). Recently, PACS2 mutations have been causally linked to a DEE with cerebellar dysgenesis and facial dysmorphism. All known patients presented with a recurrent de novo missense mutation, c.625G>A (p.Glu209Lys). Here, we report on a 7-year-old boy with DEE, cerebellar dysgenesis, facial dysmorphism and postnatal growth delay, apparently not fitting with any recognized disorder. WES disclosed a de novo novel missense PACS2 variant, c.631G>A (p.Glu211Lys), as the molecular cause of this complex phenotype. We provide a detailed clinical characterization of this patient, and analyse the available clinical data of individuals with PACS2 mutations to delineate more accurately the clinical spectrum associated with this recently described syndrome. Our study expands the clinical and molecular spectrum of PACS2 mutations. Overview of the available clinical data allow to delineate the condition associated with PACS2 mutations as a variable trait, in which the key features are represented by moderate to severe ID, cerebellar dysgenesis and other CNS malformations, reduced growth, and facial dysmorphism.

AB - Whole exome sequencing (WES) has led to the understanding of the molecular events affecting neurodevelopment in an extremely diverse clinical context, including diseases with intellectual disability (ID) associated with variable central nervous system (CNS) malformations, and developmental and epileptic encephalopathies (DEEs). Recently, PACS2 mutations have been causally linked to a DEE with cerebellar dysgenesis and facial dysmorphism. All known patients presented with a recurrent de novo missense mutation, c.625G>A (p.Glu209Lys). Here, we report on a 7-year-old boy with DEE, cerebellar dysgenesis, facial dysmorphism and postnatal growth delay, apparently not fitting with any recognized disorder. WES disclosed a de novo novel missense PACS2 variant, c.631G>A (p.Glu211Lys), as the molecular cause of this complex phenotype. We provide a detailed clinical characterization of this patient, and analyse the available clinical data of individuals with PACS2 mutations to delineate more accurately the clinical spectrum associated with this recently described syndrome. Our study expands the clinical and molecular spectrum of PACS2 mutations. Overview of the available clinical data allow to delineate the condition associated with PACS2 mutations as a variable trait, in which the key features are represented by moderate to severe ID, cerebellar dysgenesis and other CNS malformations, reduced growth, and facial dysmorphism.

U2 - 10.1111/cge.13516

DO - 10.1111/cge.13516

M3 - Article

VL - 95

SP - 525

EP - 531

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 4

ER -