title: Broadening the phenotypic spectrum of pathogenic LARP7 variants: two cases with intellectual disability, variable growth retardation and distinct facial features.
abstract: In 2012 Alazami et al. described a novel syndromic cause of primordial dwarfism with distinct facial features and severe intellectual disability. A homozygous frameshift mutation in LARP7, a chaperone of the noncoding RNA 7SK, was discovered in patients from a single consanguineous Saudi family. To date, only one additional patient has recently been described. To further delineate the phenotype associated with LARP7 mutations, we report two additional cases originating from the Netherlands and Saudi Arabia. The patients presented with intellectual disability, distinct facial features and variable short stature. We describe their clinical features and compare them with the previously reported patients. Both cases were identified by diagnostic whole-exome sequencing, which detected two homozygous pathogenic LARP7 variants: c.1091_1094delCGGT in the Dutch case and c.1045_1051dupAAGGATA in the Saudi Arabian case. Both variants are leading to frameshifts with introduction of premature stop codons, suggesting that loss of function is likely the disease mechanism. This study is an independent confirmation of the syndrome due to LARP7 depletion. Our cases broaden the associated clinical features of the syndrome and contribute to the delineation of the phenotypic spectrum of LARP7 mutations.
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Iris H I M
authors.initials: IH
authors.lastname: Hollink
authors.affiliation: Division of Genetics, Department of Pediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Majid
authors.initials: M
authors.lastname: Alfadhel
authors.affiliation: Division of Genetics, Department of Pediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Anwar S
authors.initials: AS
authors.lastname: Al-Wakeel
authors.affiliation: Division of Genetics, Department of Pediatrics, King Saud bin Abdulaziz University for Health Sciences, King Abdullah Specialized Children's Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Farough
authors.initials: F
authors.lastname: Ababneh
authors.affiliation: Department of Human Genetics, Division of Genome Diagnostics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Rolph
authors.initials: R
authors.lastname: Pfundt
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Pediatrics, Amphia Hospital, Breda, The Netherlands.
authors.forename: Stella A
authors.initials: SA
authors.lastname: de Man
authors.affiliation: Centogene AG, Rostock, Germany.
authors.forename: Rami Abou
authors.initials: RA
authors.lastname: Jamra
authors.affiliation: Centogene AG, Rostock, Germany.|Albrecht-Kossel-Institute for Neuroregeneration, Medical University Rostock, Rostock, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Rolfs
authors.affiliation: Centogene AG, Rostock, Germany.
authors.forename: Aida M
authors.initials: AM
authors.lastname: Bertoli-Avella
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Ingrid M B H
authors.initials: IM
authors.lastname: van de Laar
mesh_terms: D002648:Child; D002675:Child, Preschool; D019066:Facies; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010641:Phenotype; D012261:Ribonucleoproteins / Q000235:genetics*
chemical_list: C528908:Larp7 protein, human; D012261:Ribonucleoproteins