title: Mulibrey nanism: Two novel mutations in a child identified by Array CGH and DNA sequencing.
abstract: In childhood, several rare genetic diseases have overlapping symptoms and signs, including those regarding growth alterations, thus the differential diagnosis is sometimes difficult. The proband, aged 3 years, was suspected to have Silver-Russel syndrome because of intrauterine growth retardation, postnatal growth retardation, typical facial dysmorphic features, macrocephaly, body asymmetry, and bilateral fifth finger clinodactyly. Other features were left atrial and ventricular enlargement and patent foramen ovale. Total X-ray skeleton showed hypoplasia of the twelfth rib bilaterally and of the coccyx, slender long bones with thick cortex, and narrow medullary channels. The genetic investigation did not confirm Silver-Russel syndrome. At the age of 5 the patient developed an additional sign: hepatomegaly. Array CGH revealed a 147 kb deletion (involving TRIM 37 and SKA2 genes) on one allele of chromosome 17, inherited from his mother. These results suggested Mulibrey nanism. The clinical features were found to fit this hypothesis. Sequencing of the TRIM 37 gene showed a single base change at a splicing locus, inherited from his father that provoked a truncated protein. The combined use of Array CGH and DNA sequencing confirmed diagnosis of Mulibrey nanism. The large deletion involving the SKA2 gene, along with the increased frequency of malignant tumours in mulibrey patients, suggests closed monitoring for cancer of our patient and his mother. Array CGH should be performed as first tier test in all infants with multiple anomalies. The clinician should reconsider the clinical features when the genetics suggests this. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Mozzillo
authors.affiliation: CEINGE-Biotecnologie Avanzate, Naples, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Cozzolino
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Genesio
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Melis
authors.affiliation: CEINGE-Biotecnologie Avanzate, Naples, Italy.|Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Frisso
authors.affiliation: Multidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic, Second University of Naples, Naples, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Orrico
authors.affiliation: CEINGE-Biotecnologie Avanzate, Naples, Italy.|Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lombardo
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Fattorusso
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Discepolo
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Della Casa
authors.affiliation: Multidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic, Second University of Naples, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonelli
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Nitsch
authors.affiliation: CEINGE-Biotecnologie Avanzate, Naples, Italy.|IRCCS-Fondazione SDN, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
authors.affiliation: Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Franzese
mesh_terms: D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D050336:Mulibrey Nanism / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010808:Physical Examination; D022821:RNA Splice Sites; D011859:Radiography; D017422:Sequence Analysis, DNA; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D009687:Nuclear Proteins; D022821:RNA Splice Sites; D000070584:Tripartite Motif Proteins; C411745:TRIM37 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Array CGH; DNA sequencing; Silver-Russel syndrome; mulibrey nanism; short stature