Clinical Manifestations in a Girl with NAA10-Related Syndrome and Genotype-Phenotype Correlation in Females.

Ilenia Maini,Livia Garavelli,Orsetta Zuffardi,Davide Nicoli,Lara Valeri,Chiara Baldo,Steven Laurie,Francesca Peluso,Stefano G Caraffi

doi:10.3390/genes12060900

Abstract

Since 2011, eight males with an X-linked recessive disorder (Ogden syndrome, MIM #300855) associated with the same missense variant p.(Ser37Pro) in the NAA10 gene have been described. After the advent of whole exome sequencing, many NAA10 variants have been reported as causative of syndromic or non-syndromic intellectual disability in both males and females. The NAA10 gene lies in the Xq28 region and encodes the catalytic subunit of the major N-terminal acetyltransferase complex NatA, which acetylates almost half the human proteome. Here, we present a young female carrying a de novo NAA10 [NM_003491:c.247C > T, p.(Arg83Cys)] variant. The 18-year-old girl has severely delayed motor and language development, autistic traits, postnatal growth failure, facial dysmorphisms, interventricular septal defect, neuroimaging anomalies and epilepsy. Our attempt is to expand and compare genotype–phenotype correlation in females with NAA10-related syndrome. A detailed clinical description could have relevant consequences for the clinical management of known and newly identified individuals.

Highlights

NAA10-related syndrome is an X-linked condition associated with defects in the Nalpha-acetyltransferase 10 (NAA10) gene
We present an overview of these 12 NAA10 variants with the corresponding phenotype and add our clinical case of a young female with syndromic intellectual disability (ID) carrying the most common de novo variant p.Arg83Cys (Table S1)
We describe a girl with severely delayed motor and language development, autistic traits, facial dysmorphism, hypotonia, epilepsy, neuroimaging anomalies, ventricular septal defect (VSD), postnatal growth failure, conductive hearing loss and skeletal abnormalities

Summary

Introduction

NAA10-related syndrome is an X-linked condition associated with defects in the Nalpha-acetyltransferase 10 (NAA10) gene. Clinical features range from a severe phenotype in males, originally described as Ogden syndrome and associated with the missense variant p.Ser37Pro [1], to a milder NAA10-related intellectual disability (ID) caused by different variants in both males and females [2]. Boys affected by Ogden syndrome had severe developmental delay, hypotonia, craniofacial abnormalities, cardiac anomalies, and early death in the first months of life, mainly due to cardiac arrythmias [1]. NAA10 encodes the catalytic subunit of the N-terminal acetyltransferase protein complex A (NatA), responsible for acetylating 40–50% of all human proteins [3]. Molecular investigations in Ogden syndrome patients revealed reduced

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