Interstitial 7q31.1 copy number variations disrupting IMMP2L gene are associated with a wide spectrum of neurodevelopmental disorders.

Stefania Gimelli,Massimiliano Leoni,Elisa Tassano,Valeria Capra,Giorgio Gimelli,Maria Cristina Schiaffino,Cristina Cuoco,Patrizia Fiorio,Marisol Mirabelli-Badenier,Maja Di Rocco

doi:10.1186/s13039-014-0054-y

Abstract

BackgroundSince the introduction of the array-CGH technique in the diagnostic workup of mental retardation, new recurrent copy number variations and novel microdeletion/microduplication syndromes were identified. These findings suggest that some genomic disorders have high penetrance but a wide range of phenotypic severity.ResultsWe present the clinical and molecular description of four unrelated patients affected by neurodevelopmental disorders and overlapping 7q31.1 microdeletion/microduplication, identified by array-CGH and involving only part of the IMMP2L gene.ConclusionIMMP2L encodes an inner mitochondrial membrane protease-like protein, which is required for processing of cytochromes inside mitochondria. Numerous studies reported that this gene is implicated in behavioural disorders such as autistic spectrum disorders, attention-deficit hyperactivity disorders, and Gilles de la Tourette syndrome. We discuss the functions of the gene suggesting that IMMP2L may act as risk factor for neurological disease.

Highlights

Since the introduction of the array-CGH technique in the diagnostic workup of mental retardation, new recurrent copy number variations and novel microdeletion/microduplication syndromes were identified
Genome-wide linkage studies have identified genomic imbalances involving IMMP2L gene in 7q31.1 that are associated with autistim spectrum disorders (AUTS9) (MIM 611015) [2], attention deficit/hyperactivity disorder (ADHD) (MIM 143465) [3] and Gilles de la Tourette syndrome (GTS) (MIM 137580) [4,5,6,7]
Autism spectrum disorders (ASD) are a subset of complex neurodevelopmental disorders characterized by reduced reciprocal social interaction, impaired ability to communicate, and a narrow range of interests and repetitive behaviours

Summary

Introduction

Since the introduction of the array-CGH technique in the diagnostic workup of mental retardation, new recurrent copy number variations and novel microdeletion/microduplication syndromes were identified. These findings suggest that some genomic disorders have high penetrance but a wide range of phenotypic severity. Genome-wide linkage studies have identified genomic imbalances involving IMMP2L gene in 7q31.1 that are associated with autistim spectrum disorders (AUTS9) (MIM 611015) [2], attention deficit/hyperactivity disorder (ADHD) (MIM 143465) [3] and Gilles de la Tourette syndrome (GTS) (MIM 137580) [4,5,6,7]. GTS is a neurobehavioral disorder characterized by motor and vocal tics and behavioural abnormalities usually appearing between 3 and 8 years of age

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