Contents lists available at ScienceDirect European Journal of Medical Genetics journal homepage: www.elsevier.com/locate/ejmg Refinement of the critical 7p22.1 deletion region: Haploinsufficiency of ACTB is the cause of the 7p22.1 microdeletion-related developmental disorders Orazio Palumbo a,1 , Maria Accadia b,1 , Pietro Palumbo a , Maria Pia Leone a,c , Antonio Scorrano d , Teresa Palladino a , Raffaella Stallone a , Maria Clara Bonaglia e , Massimo Carella a,* a Division of Medical Genetics, Poliambulatorio “Giovanni Paolo II”, IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013 San Giovanni Rotondo, FG, Italy b Medical Genetics Service, Hospital “Cardinale G. Panico”, Via San Pio X n°4, 73039 Tricase, LE, Italy c Department of Soil, Plant and Food Science, University of Bari “Aldo Moro”, Via Amendola 165/A, 70126 Bari, Italy d Pediatrics and Neonatology Unit, Hospital “Cardinale G. Panico”, Via San Pio X n°4, 73039 Tricase, LE, Italy e Cytogenetic Laboratory, Scientific Institute ‘‘Eugenio Medea’’, via Don Luigi Monza 20, 23842 Bosisio Parini, LC, Italy ARTICLE INFO Keywords: 7p22.1 microdeletion ACTB Chromosomal microarray analysis ABSTRACT Non-recurrent microdeletion (≤2 Mb in size) in 7p22.1 is a rarely described cytogenetic aberration, only re- cently reported in patients with developmental delay/intellectual disability, short stature and microcephaly. The size of the deletions ranged from 0.37 to 1.5 Mb, and reported genotype-phenotype correlations identified a minimum deleted region of 0.37 Mb involving the FBLX18, ACTB, FSCN1, RNF216 and ZNF815P genes. The authors suggested that deletion of ACTB, which encodes β-actin, an essential component of the cytoskeleton, could be responsible for the clinical features observed in the patients with a 7p22.1 microdeletion. Here, we describe a 23-month-old child displaying developmental delay, short stature, microcephaly and distinctive facial features. Chromosomal microarray analysis performed using high-resolution SNP-array platform revealed a de novo interstitial 60 Kb microdeletion in the 7p22.1 region (from 5,509,127 bp to 5,569,096 bp, hg19) encom- passing only two genes: FBXL18 and ACTB. To the best of our knowledge, this is the smallest deletion at 7p22.1 to date reported in medical literature (Pubmed). Combining our data with phenotypic and genotypic data of cases from literature, we were able to narrow the minimal critical region, which contained only two genes, i.e., FBXL18 and ACTB. Our finding is useful to perform a more accurate genotype-phenotype correlation and strongly strengthen the hypothesis that haploinsufficiency of ACTB is the main cause of the clinical phenotype observed in the patients with 7p22.1 microdeletions, facilitating genetic diagnosis and counseling. 1. Introduction De novo microdeletions/microduplications encompassing one or few genes are an easy way to identify genes involved in developmental disorders. Interstitial microdeletions involving the 7p22.1 chromo- somal region are very rare, since were recently described in only five cases with developmental delay/intellectual disability, short stature and microcephaly (Shimojima et al., 2016). From a molecular point of view, two of the five patients showed a very small deletion, that al- lowed the authors to identify a genomic region encompassing the FBLX18, ACTB, FSCN1, RNF216 and ZNF815P genes as the “minimal critical region” (MCR). From a medical point of view, since the clinical relevance of the FBLX18, FSCN1 and ZNF815P genes was unknown, the authors focused their attention on the remaining two. In particular, they proposed the haploinsufficiency of ACTB as responsible for the clinical manifestations of 7p22.1 microdeletions. Here, we describe a patient with developmental delay, short stature, microcephaly and dysmorphic features carriers of the smallest inter- stitial de novo microdeletion inside the chromosomal region 7p22.1 reported to date encompassing the FBLX18 and ACTB genes. We com- pared molecular findings as well as clinical presentation of our patient and previously reported cases with deletions involving the ACTB gene discussing its role in the etiology of the observed clinical phenotype. https://doi.org/10.1016/j.ejmg.2017.12.008 Received 25 October 2017; Received in revised form 27 November 2017; Accepted 16 December 2017 * Corresponding author. 1 These authors contributed equally to this work. E-mail address: m.carella@operapadrepio.it (M. Carella). European Journal of Medical Genetics xxx (xxxx) xxx–xxx 1769-7212/ © 2017 Elsevier Masson SAS. All rights reserved. Please cite this article as: Palumbo, O., European Journal of Medical Genetics (2017), https://doi.org/10.1016/j.ejmg.2017.12.008