The etiology of neurodevelopmental disorders and epilepsy is very heterogeneous and partly still unknown, and the research of causative genes related to these diseases is still in progress. In 2020, pathogenic variants of the TET3 gene were associated with Beck–Fahrner syndrome, which is characterized by neurodevelopmental delay, intellectual and learning disabilities of variable degree, growth abnormalities, hypotonia and seizures. Variants of TET3 have been described having both an autosomal dominant with a milder phenotype and an autosomal recessive pattern. To date, in the literature, only 28 patients are reported with pathogenic variants of the TET3 gene, and only 9 of them have epilepsy. We describe a 31-year-old woman with macrocephaly, mild neurodevelopmental delay and a long history of epilepsy. Trio-based exome sequencing identified a de novo heterozygous TET3 variant, c.2867G>A p.(Arg956Gln), never described before, absent in the general population and predicted to be potentially pathogenetic by bioinformatics tools. This report aims to describe the clinical history of our patient, the pharmacological treatment and clinical response, as well as the biological characteristics of this new variant.

BackgroundNFIA-related disorder (OMIM #613735) is an autosomal dominant neurodevelopmental disorder characterized by a variable degree of cognitive impairment and non-specific dysmorphic features. To date, fewer than thirty patients affected by this disorder have been described.MethodsOur study included three children with NFIA haploinsufficiency recruited from three medical genetics centers. Clinical presentations were recorded on a standardized case report form.ResultsAll patients presented a variable degree of intellectual disability. None of the individuals in our cohort had urinary tract malformations. Three novel mutations, c.344G>A, c.261T>G, and c.887_888del are reported here.ConclusionNFIA haploinsufficiency can be suspected through careful observation of specific dysmorphisms, including macrocephaly and craniofacial abnormalities. Instrumental tests such as MRI and renal ultrasound provide further diagnostic clues, while genetic testing can confirm the diagnosis.

The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20–40 genes, respectively. The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G/BBB and Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare and characterized mainly by normal phenotype or mild intellectual disability and variable clinical features. The pathogenetic mechanisms underlying this disorder are not completely understood. Because the 22q11.2 region harbours genes coding for transcriptional factors and chromatin remodelers, in this study, we performed analysis of genome-wide DNA methylation of peripheral blood from 49 patients with 22q11.2DS using the Illumina Infinium Methylation EPIC bead chip arrays. This cohort comprises 43 typical, 2 proximal and 4 distal deletions. We demonstrated the evidence of a unique and highly specific episignature in all typical and proximal 22q11.2DS. The sensitivity and specificity of this signature was further confirmed by comparing it to over 1500 patients with other neurodevelopmental disorders with known episignatures. Mapping the 22q11.2DS DNA methylation episignature provides both novel insights into the molecular pathogenesis of this disorder and an effective tool in the molecular diagnosis of 22q11.2DS.

In recent years, a rare form of autosomal recessive brachyolmia associated with amelogenesis imperfecta (AI) has been described as a novel nosologic entity. This disorder is characterized by skeletal dysplasia (e.g., platyspondyly, short trunk, scoliosis, broad ilia, elongated femoral necks with coxa valga) and severe enamel and dental anomalies. Pathogenic variants in the latent transforming growth factor-β binding protein 3 (LTBP3) gene have been found implicated in the pathogenesis of this disorder. So far, biallelic pathogenic LTBP3 variants have been identified in less than 10 families. We here report a young boy born from consanguineous parents with a complex phenotype including skeletal dysplasia associated with aortic stenosis, hypertrophic cardiomyopathy, hypodontia and amelogenesis imperfecta caused by a previously unreported homozygous LTBP3 splice site variant. We also compare the genotypes and phenotypes of patients reported to date. This work provides further evidence that brachyolmia with amelogenesis imperfecta is a distinct nosologic entity and that variations in LTBP3 are involved in its pathogenesis.

Feingold Syndrome type 1 (FS1) is an autosomal dominant disorder due to a loss of function mutations in the MYCN gene. FS1 is generally clinically characterized by mild learning disability, microcephaly, short palpebral fissures, short stature, brachymesophalangy, hypoplastic thumbs, as well as syndactyly of toes, variably associated with organ abnormalities, the most common being gastrointestinal atresia. In current literature, more than 120 FS1 patients have been described, but diagnostic criteria are not well agreed upon, likewise the genotype-phenotype correlations are not well understood. Here, we describe 11 FS1 patients, belonging to six distinct families, where we have identified three novel MYCN mutations along with three pathogenetic variants, the latter which have already been reported. Several patients presented a mild phenotype of the condition and they have been diagnosed as being affected only after segregation analyses of the MYCN mutation identified in the propositus. We also describe here the first ever FS1 patient with severe intellectual disability having a maternally inherited MYCN variant together with an additional GNAO1 mutation inherited paternally. Mutations in the GNAO1 gene are associated with a specific form of intellectual disability and epilepsy, thus the finding of two different rare diseases in the same patient could explain his severe phenotype. Therein, a thorough investigation is merited into the possibility that additional variants in patients with a MYCN mutation and severe phenotype do exist. Finally, in order to guarantee a more reliable diagnosis of FS1, we suggest using both major and minor clinical-molecular diagnostic criteria.

American Journal of Medical Genetics Part AVolume 182, Issue 10 p. 2197-2201 ISSUE INFORMATIONFree Access Table of Contents, Volume 182A, Number 10, October 2020 First published: 15 September 2020 https://doi.org/10.1002/ajmg.a.61245AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume182, Issue10October 2020Pages 2197-2201 RelatedInformation

Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5-year-old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole-exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen-magnetic resonance spectroscopy (H-MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7-related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth.

Schilbach–Rott syndrome (SRS, OMIM%164220) is a disorder of unknown aetiology that is characterised by hypotelorism, epichantal folds, cleft palate, dysmorphic face, hypospadia in males and mild mental retardation in some patients. To date, 5 families and 17 patients have exhibited this phenotype, and recurrence in two of these families suggests an autosomal dominant inheritance. SRS overlaps with a mild form of holoprosencephaly (HPE), but array–CGH analysis and sequencing of some HPE-related genes (SEPT9, SHH and TWIST) did not reveal any variants in at least one family. Herein, we investigated by array–CGH analysis a 11-year-old female patient and her father, both exhibiting the typical SRS phenotype, disclosing in the daughter–father couple the same microduplication of chromosome 9q22.32q22.33 [arr[hg19]9q22.32(98,049,611_98,049,636)x3,9q22.33 (99,301,483_99,301,508)x3], involving eight genes, including PTCH1. The duplication segregated with the disease, since it was not found in the healthy paternal grandparents of the proband. The gain-of-function variants of the PTCH1 gene are responsible for a mild form of HPE. This is the first genetic variant found in SRS. This finding reinforces the hypothesis that SRS belongs to the HPE clinical spectrum and suggests to perform array–CGH in patients with SRS phenotype and, if negative, to consider a potential benefit from sequencing of HPE-related genes.

Heterozygous mutations in the SHOX gene or in the upstream and downstream enhancer elements are associated with 2-22% of cases of idiopathic short stature (OMIM #300582) and with 60% of cases of Leri-Weill dyschondrosteosis (OMIM #127300) with which female subjects are generally more severely affected. Approximately 80-90% of SHOX pathogenic variants are deletions or duplications, and the remaining 10-20% are point mutations that primarily give rise to missense variants. The clinical interpretation of novel variants, particularly missense variants, can be challenging and can remain of uncertain significance. Here, we describe a novel missense variant (c. 1044 G>T, p.Arg118Met) in a Moroccan boy with a disproportionately short stature and without any radiological traits or bone deformities and in his mother, who had a disproportionately short stature and a Madelung deformity. This variant has not been reported to date in the updated SHOX allelic variant or Human Gene Mutation Databases nor is it listed as a polymorphism in the ExAC browser, dbSNP, or 1000G. This mutation was predicted to be deleterious by three different bioinformatics tools since it modifies an amino acid in a highly conserved DNA-binding domain of the SHOX protein. Based on this evidence, the patient was treated with recombinant human growth hormone.

Sotos syndrome is one of the most common overgrowth diseases and it predisposes patients to cancer, generally in childhood. The prevalence of this genetic disorder is 1:10,000–1:50,000, and it is characterized by wide allelic heterogeneity, with more than 100 different known mutations in the nuclear receptor-binding SET domain containing protein 1 (NSD1) gene. Most of these alterations are deletions and common micro-deletions with haploinsufficiency. Singular variants are missense mutations. The present study reports a case of a 4-year-old boy with specific clinical features of Sotos syndrome and a particular complex skin hamartoma on the right femoral side, in addition to other minor findings, such as a “café-au-lait” spot on the right hemithorax and syndactyly of the second and third right toes. NSD1 gene analysis identified a de novo missense mutation, “c.[5867T>A]+[=]”; “p.[Leu1956Gln]+[=]”, that was not previously described in the literature. This mutation was localized to the functional domain of the gene and was likely the cause of Sotos syndrome in our patient. We also compared aspects of our patient’s condition with the clinical features of tuberous sclerosis (TSC), which is an autosomal neurocutaneous syndrome caused by mutations in the TSC1/TSC2 genes. These genes control cell growth and cell survival. This disorder is characterized by hamartomas in multiple organ systems, several coetaneous abnormalities, epilepsy, and increased risk of several types of tumors.

Context: Familial isolated hypoparathyroidism (FIH) is a genetically heterogeneous disorder due to mutations of the calcium-sensing receptor (CASR), glial cells missing-2 (GCM2), guanine nucleotide binding protein alpha 11 (GNA11), or parathyroid hormone (PTH) genes. Thus far, only four cases with homozygous and two cases with heterozygous mutations in the PTH gene have been reported. Objective: To clinically describe an FIH family and identify and characterize the causal gene mutation. Design: Genomic DNA of the family members was subjected to CASR, GCM2, GNA11, and PTH gene mutational analysis. Functional assays were performed on the variant identified. Participants: Six subjects of a three-generation FIH family with three affected individuals having severe hypocalcemia and inappropriately low serum PTH. Results: No mutations were detected in the CASR, GCM2, and GNA11 genes. A heterozygous variant that segregated with the disease was identified in PTH gene exon 2 (c.41T. A > p.M14K). This missense variant, in the hydrophobic core of the signal sequence, was predicted in silico to impair cleavage of preproPTH to proPTH. Functional assays in HEK293 cells demonstrated much greater retention intracellularly but impaired secretion into the medium of the M14K mutant relative to wild type. The addition of the pharmacological chaperone, 4-phenylbutyric acid, led to a reduction of cellular retention and increased accumulation in the cell medium of the M14K mutant. Conclusions: We report a heterozygous PTH mutation in an FIH family and demonstrate accumulation of the mutant intracellularly and its impaired secretion. An accurate genetic diagnosis in such hypoparathyroid patients is critical for appropriate treatment and genetic counseling.

Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterised by the progressive occlusion of the internal carotid artery. Its aetiology is uncertain, but a genetic background seems likely, given the high MA familial rate. To investigate the aetiology of craniosynostosis and juvenile moyamoya in a 14-year-old male patient, we performed an array-comparative genomic hybridisation revealing a de novo interstitial deletion of 8.5 Mb in chromosome region 1p32p31. The deletion involved 34 protein coding genes, including NF1A, whose haploinsufficiency is indicated as being mainly responsible for the 1p32-p31 chromosome deletion syndrome phenotype (OMIM 613735). Our patient also has a deleted FOXD3 of the FOX gene family of transcription factors, which plays an important role in neural crest cell growth and differentiation. As the murine FOXD3−/− model shows craniofacial anomalies and abnormal common carotid artery morphology, it can be hypothesised that FOXD3 is involved in the pathogenesis of the craniofacial and vascular defects observed in our patient. In support of our assumption, we found in the literature another patient with a syndromic form of MA who had a deletion involving another FOX gene (FOXC1). In addition to describing the clinical history of our patient, we have reviewed all of the available literature concerning other patients with a 1p32p31 deletion, including cases from the Decipher database, and we have also reviewed the genetic disorders associated with MA, which is a useful guide for the diagnosis of syndromic form of MA.

Genetic testing strategies and counseling in cystic fibrosis (CF) can be problematic due to its extreme allelic heterogeneity and the difficult clinical interpretation of rare variants. Since in a previous survey of Italian CF patients, Umbria (a small region with about 900,000 inhabitants) was excluded due to the low number of chromosomes tested (<50), we have performed a comprehensive retrospective clinical and molecular survey of 62 CF patients coming from this region. We have summarized all the genotypic and phenotypic data in a table, and we interviewed the older patients in order to obtain a comprehensive overview of their conditions. We found that the c.2052_2053insA (2184insA) variant, a class I mutation with high frequency in Eastern Europe but very rare in Italy, is the fourth most frequent allele in Umbria. The 2184insA variant was not included in the first-level regional screening, and we therefore suggest the implementation of this variant in the future.

Mutations of the MED12 gene have been reported mainly in males with FG (Opitz–Kaveggia), Lujan–Fryns, or X‐linked Ohdo syndromes. Recently, a different phenotype characterized by minor anomalies, severe intellectual disability (ID), and absent language was reported in female and male patients belonging to the same family and carrying a frameshift MED12 mutation (c.5898dupC). Here, we report on two brothers and their niece affected by severe and mild ID, respectively, where whole exome sequencing combined with variant analysis within a panel of ID‐related genes, disclosed a novel c.2312T>C (p.Ile771Thr) MED12 mutation. This variant, which has not been reported as a polymorphism, was not present in a third unaffected brother, and was predicted to be deleterious by five bioinformatic databases. This finding together with the phenotypic analogies shared with the carriers of c.5898dupC mutation suggests the existence of a fourth MED12‐related disorder, characterized by severe ID, absent or deficient language and, milder, clinical manifestation in heterozygotes. We have reviewed the literature on MED12 heterozygotes, their clinical manifestations, and discuss the possible biological causes of this condition. © 2016 Wiley Periodicals, Inc.

American Journal of Medical Genetics Part AVolume 155, Issue 4 p. fm i-fm v Table of ContentsFree Access Table of Contents, Volume 155, Number 4, April 2011 First published: 24 March 2011 https://doi.org/10.1002/ajmg.a.34033AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume155, Issue4April 2011Pages fm i-fm v RelatedInformation

American Journal of Medical Genetics Part AVolume 155, Issue 1 p. fm i-fm iv Table of ContentsFree Access Table of Contents, Volume 155, Number 1, January 2011 First published: 22 February 2011 https://doi.org/10.1002/ajmg.a.33889AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume155, Issue1January 2011Pages fm i-fm iv RelatedInformation

American Journal of Medical Genetics Part AVolume 155, Issue 4 p. 928-930 Research Letter Trisomy 2 mosaicism with caudal dysgenesis, Hirschsprung disease, and micro-anophthalmia† Paolo Prontera, Paolo Prontera Medical Genetics Unit, Department of Clinical and Experimental Medicine, University of Perugia and "S. Maria della Misericordia" Hospital, Perugia, ItalySearch for more papers by this authorGabriela Stangoni, Gabriela Stangoni Neonatology Unit, "S. Maria della Misericordia" Hospital, Perugia, ItalySearch for more papers by this authorCarmela Ardisia, Carmela Ardisia Medical Genetics Unit, Department of Clinical and Experimental Medicine, University of Perugia and "S. Maria della Misericordia" Hospital, Perugia, ItalySearch for more papers by this authorDaniela Rogaia, Daniela Rogaia Medical Genetics Unit, Department of Clinical and Experimental Medicine, University of Perugia and "S. Maria della Misericordia" Hospital, Perugia, ItalySearch for more papers by this authorAmedea Mencarelli, Amedea Mencarelli Medical Genetics Unit, Department of Clinical and Experimental Medicine, University of Perugia and "S. Maria della Misericordia" Hospital, Perugia, ItalySearch for more papers by this authorEmilio Donti, Corresponding Author Emilio Donti genetica@unipg.it Medical Genetics Unit, Department of Clinical and Experimental Medicine, University of Perugia and "S. Maria della Misericordia" Hospital, Perugia, ItalyUniversità e Azienda Ospedaliera di Perugia, Sezione di Genetica Medica, Via E. dal Pozzo, 06123 Perugia, Italy.Search for more papers by this author Paolo Prontera, Paolo Prontera Medical Genetics Unit, Department of Clinical and Experimental Medicine, University of Perugia and "S. Maria della Misericordia" Hospital, Perugia, ItalySearch for more papers by this authorGabriela Stangoni, Gabriela Stangoni Neonatology Unit, "S. Maria della Misericordia" Hospital, Perugia, ItalySearch for more papers by this authorCarmela Ardisia, Carmela Ardisia Medical Genetics Unit, Department of Clinical and Experimental Medicine, University of Perugia and "S. Maria della Misericordia" Hospital, Perugia, ItalySearch for more papers by this authorDaniela Rogaia, Daniela Rogaia Medical Genetics Unit, Department of Clinical and Experimental Medicine, University of Perugia and "S. Maria della Misericordia" Hospital, Perugia, ItalySearch for more papers by this authorAmedea Mencarelli, Amedea Mencarelli Medical Genetics Unit, Department of Clinical and Experimental Medicine, University of Perugia and "S. Maria della Misericordia" Hospital, Perugia, ItalySearch for more papers by this authorEmilio Donti, Corresponding Author Emilio Donti genetica@unipg.it Medical Genetics Unit, Department of Clinical and Experimental Medicine, University of Perugia and "S. Maria della Misericordia" Hospital, Perugia, ItalyUniversità e Azienda Ospedaliera di Perugia, Sezione di Genetica Medica, Via E. dal Pozzo, 06123 Perugia, Italy.Search for more papers by this author First published: 17 March 2011 https://doi.org/10.1002/ajmg.a.33817Citations: 6 † How to Cite this Article: Prontera P, Stangoni G, Ardisia C, Rogaia D, Mencarelli A, Donti E. 2011. Trisomy 2 mosaicism with caudal dysgenesis, Hirschsprung disease and micro-anophthalmia. Am J Med Genet Part A 155:928–930. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume155, Issue4April 2011Pages 928-930 RelatedInformation

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare condition belonging to the group of ectodermal dysplasias caused by TP63 mutations. Its clinical phenotype is similar to ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) and limb-mammary syndrome (LMS), and differs from these disorders mainly by the absence of cleft lip and/or palate. We report on a 39-year-old patient who was found to be heterozygous for a c.401G > T (p.Gly134Val) de novo mutation of TP63. This patient had the ADULT phenotype associated with cleft palate. Our findings, rather than extend the clinical spectrum of ADULT syndrome, suggest that cleft palate can no longer be considered an element for differential diagnosis for ADULT, EEC, and LMS. Our data, added to other reports on overlapping phenotypes, support the combining of these three phenotypes into a unique entity that we propose to call "ELA syndrome," which is an acronym of ectrodactyly-ectodermal dysplasia-cleft lip and palate, limb-mammary, and ADULT syndromes.

American Journal of Medical Genetics Part AVolume 155, Issue 1 p. 221-224 Research Letter FMR1, FMR2, and SLITRK2 deletion inside a paracentric inversion involving bands Xq27.3–q28 in a male and his mother† Simona Cavani, Corresponding Author Simona Cavani [email protected] Laboratory of Genetics, Galliera Hospital, Genoa, ItalyLaboratory of Genetics, Galliera Hospital, Via A. Volta 10, 16128 Genova, Italy.Search for more papers by this authorPaolo Prontera, Paolo Prontera Medical Genetics Unit, University and Hospital of Perugia, Perugia, ItalySearch for more papers by this authorMarina Grasso, Marina Grasso Laboratory of Genetics, Galliera Hospital, Genoa, ItalySearch for more papers by this authorCarmela Ardisia, Carmela Ardisia Medical Genetics Unit, University and Hospital of Perugia, Perugia, ItalySearch for more papers by this authorMichela Malacarne, Michela Malacarne Laboratory of Genetics, Galliera Hospital, Genoa, ItalySearch for more papers by this authorCristina Gradassi, Cristina Gradassi Medical Genetics Unit, University and Hospital of Perugia, Perugia, ItalySearch for more papers by this authorMassimiliano Cecconi, Massimiliano Cecconi Laboratory of Genetics, Galliera Hospital, Genoa, ItalySearch for more papers by this authorAmedea Mencarelli, Amedea Mencarelli Medical Genetics Unit, University and Hospital of Perugia, Perugia, ItalySearch for more papers by this authorEmilio Donti, Emilio Donti Medical Genetics Unit, University and Hospital of Perugia, Perugia, ItalySearch for more papers by this authorMauro Pierluigi, Mauro Pierluigi Laboratory of Genetics, Galliera Hospital, Genoa, ItalySearch for more papers by this author Simona Cavani, Corresponding Author Simona Cavani [email protected] Laboratory of Genetics, Galliera Hospital, Genoa, ItalyLaboratory of Genetics, Galliera Hospital, Via A. Volta 10, 16128 Genova, Italy.Search for more papers by this authorPaolo Prontera, Paolo Prontera Medical Genetics Unit, University and Hospital of Perugia, Perugia, ItalySearch for more papers by this authorMarina Grasso, Marina Grasso Laboratory of Genetics, Galliera Hospital, Genoa, ItalySearch for more papers by this authorCarmela Ardisia, Carmela Ardisia Medical Genetics Unit, University and Hospital of Perugia, Perugia, ItalySearch for more papers by this authorMichela Malacarne, Michela Malacarne Laboratory of Genetics, Galliera Hospital, Genoa, ItalySearch for more papers by this authorCristina Gradassi, Cristina Gradassi Medical Genetics Unit, University and Hospital of Perugia, Perugia, ItalySearch for more papers by this authorMassimiliano Cecconi, Massimiliano Cecconi Laboratory of Genetics, Galliera Hospital, Genoa, ItalySearch for more papers by this authorAmedea Mencarelli, Amedea Mencarelli Medical Genetics Unit, University and Hospital of Perugia, Perugia, ItalySearch for more papers by this authorEmilio Donti, Emilio Donti Medical Genetics Unit, University and Hospital of Perugia, Perugia, ItalySearch for more papers by this authorMauro Pierluigi, Mauro Pierluigi Laboratory of Genetics, Galliera Hospital, Genoa, ItalySearch for more papers by this author First published: 10 December 2010 https://doi.org/10.1002/ajmg.a.33515Citations: 8 † How to Cite this Article: Cavani S, Prontera P, Grasso M, Ardisia C, Malacarne M, Gradassi C, Cecconi M, Mencarelli A, Donti E, Pierluigi M. 2010. FMR1, FMR2, and SLITRK2 deletion inside a paracentric inversion involving bands Xq27.3–q28 in a male and his mother. Am J Med Genet Part A 155:221–224. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES Aruga J, Mikoshiba K. 2003. Identification and characterization of Slitrk, a novel neuronal transmembrane protein family controlling neurite outgrowth. Mol Cell Neurosci 24: 117–129. Aruga J, Yokota N, Mikoshiba K. 2003. Human SLITRK family genes: Genomic organization and expression profilino in normal brain and brain tumor tissue. Gene 315: 87–94. Birot AM, Delobel B, Gronnier P, Bonnet V, Maire I, Bozon D. 1996. A 5-megabase familial deletion removes the IDS and FMR-1 genes in a male Hunter patient. Hum Mutat 7: 266–268. Clarke JT, Wilson PJ, Morris CP, Hopwood JJ, Richards RI, Sutherland GR, Ray PN. 1992. Characterization of a deletion ai Xq27–q28 associated with unbalanced inactivation of the non-mutant X chromosome. Am J Hum Genet 51: 316–322. Coffee B, Ikeda M, Budimirovic DB, Hjelm LN, Kaufmann WE, Warren ST. 2008. Mosaic FMR1 deletion causes Fragile X syndrome and can lead to molecular misdiagnosis: A case report and review of the literature. Am J Med Genet Part A 146A: 1358–1367. Dahl N, Hu LJ, Chery M, Fardeau M, Gilgenkrantz S, Nivelon-Chevallier A, Sidaner-Noisette I, Mugneret F, Gouyon JB, Gal A. 1995. Myotubular myopathy in a girl with a deletion at Xq27–q28 and unbalanced X inactivation assigns the MTM1 gene to a 600-kb region. Am J Hum Genet 56: 1108–1115. Fengler S, Fuchs S, Konig R, Arnemann J. 2002. Mosaicism for FMR1 and FMR2 deletion: A new case. J Med Genet 30: 761–766. Moore SJ, Strain L, Cole GF, Miedzzybrodzka Z, Kelly KF, Dean JC. 1999. Fragile X syndrome with FMR1 and FMR2 deletion. J Med Genet 33: 338–340. Online Mendelian Inheritance in Man, OMIM (TM). 2010. McKusick–Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD). http://www.ncbi.nlm.nih.gov/omim/. Penagarikano O, Mulle JG, Warren ST. 2007. The pathophysiology of fragile X syndrome. Annu Rev Genomics Hum Genet 8: 108–129. Plagnol V, Uz E, Wallace C, Stevens H, Clayton D, Ozcelik T, Todd JA. 2008. Extreme clonality in lymphoblastoid cell lines with implications for allele specific expression analyses. PLoS ONE 3: e2966. DOI: 10.1371/journal.pone.0002966. Probst FJ, Roeder ER, Enciso VB, Ou Z, Cooper ML, Eng P, Li J, Gu Y, Stratton RF, Chinault AC, Shaw CA, Sutton VR, Cheung SW, Nelson DL. 2007. Chromosomal microarray analysis (CMA) detects a large X chromosome deletion including FMR1, FMR2, and IDS in a female patient with mental retardation. Am J Med Genet Part A 143A: 1358–1365. Smith EN, Bloss CS, Badner JA, Barrett T, Belmonte PL, Berrettini W, Byerley W, Coryell W, Craig D, Edenberg HJ, Eskin E, Foroud T, Gershon E, Greenwood TA, Hipolito M, Koller DL, Lawson WB, Liu C, Lohoff F, McInnis MG, McMahon FJ, Mirel DB, Murray SS, Nievergelt C, Nurnberger J, Nwulia EA, Paschall J, Potash JB, Rice J, Schulze TG, Scheftner W, Panganiban C, Zaitlen N, Zandi PP, Zöllner S, Schork NJ, Kelsoe JR. 2009. Genome-wide association study of bipolar disorder in European American and African American individuals. Mol Psychiatry 14: 755–763. Turner G, Webb T, Wake S, Robinson H. 1996. Prevalence of fragile X syndrome. Am J Med Genet 64: 196–197. Wolff DJ, Gustashaw KM, Zurcher V, Ko L, White W, Weiss L, Van Dyke DL, Schwartz S, Willard HF. 1997. Deletions in Xq26.3–q27.3 including FMR1 result in a severe phenotype in a male and variable phenotypes in females depending upon the X inactivation pattern. Hum Genet 100: 256–261. Citing Literature Volume155, Issue1January 2011Pages 221-224 ReferencesRelatedInformation