title: Clinical and molecular characterization of a boy with intellectual disability, facial dysmorphism, minor digital anomalies and a complex IL1RAPL1 intragenic rearrangement.
abstract: X-linked intellectual disability accounts for 10-12% of cases of cognitive impairment in males. Mutations in IL1RAPL1 are an emerging form of apparently non-syndromic X-linked intellectual disability. We report a 8-year-old intellectually disabled boy with speech delay, and unusual facial and digital anomalies who showed a novel and complex IL1RAPL1 rearrangement. It was defined by two intragenic non-contiguous duplications inherited from the unaffected mother. Chromosome X inactivation study on the mother's blood leukocytes, urinary sediment and buccal swab did not show a significant skewed inactivation. Comparison with previously described patients with IL1RAPL1 disruption was carried. Although data on craniofacial features were scanty in many papers, subtle facial dysmorphism with a thin upper lip seemed a quietly represented picture without any other genotype-phenotype correlations. Our study expands the molecular repertoire of IL1RAPL1 mutations in intellectual disability and points out the need of more accurate clinical descriptions to better define the related phenotype.
authors.affiliation: Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy. Electronic address: luigi.laino@uniroma1.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Laino
authors.affiliation: Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Bottillo
authors.affiliation: Department of Pediatrics and Child Neuropsychiatry, Sapienza University, Policlinico Umberto I University Hospital, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Piedimonte
authors.affiliation: Unit of Cytogenetics, Mendel Laboratory, Casa Sollievo della Sofferenza Foundation, San Giovanni Rotondo, FG, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bernardini
authors.affiliation: Unit of Cytogenetics, Mendel Laboratory, Casa Sollievo della Sofferenza Foundation, San Giovanni Rotondo, FG, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Torres
authors.affiliation: Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Grammatico
authors.affiliation: Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Bargiacchi
authors.affiliation: Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mulargia
authors.affiliation: Division of Pediatrics, San Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Calvani
authors.affiliation: Department of Pediatrics and Child Neuropsychiatry, Sapienza University, Policlinico Umberto I University Hospital, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cardona
authors.affiliation: Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Castori
authors.affiliation: Laboratory of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
mesh_terms: D002648:Child; D004247:DNA / Q000235:genetics; D005145:Face / Q000002:abnormalities*; D005385:Fingers / Q000002:abnormalities*; D015321:Gene Rearrangement; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics*; D007805:Language Development Disorders / Q000209:etiology / Q000235:genetics; D008046:Lip / Q000002:abnormalities; D008297:Male; D014034:Toes / Q000002:abnormalities; D049951:X Chromosome Inactivation
chemical_list: C407643:IL1RAPL1 protein, human; D053577:Interleukin-1 Receptor Accessory Protein; D004247:DNA
keywords: Duplication; Facial dysmorphism; IL1RAPL1; Intragenic; X-linked intellectual disability