RPL10 mutation segregating in a family with X-linked syndromic Intellectual Disability

• Published in: American journal of medical genetics. Part A 2015-08, Vol.167A (8), p.1908-1912
• Main Authors: Thevenon, Julien, Michot, Caroline, Bole, Christine, Nitschke, Patrick, Nizon, Mathilde, Faivre, Laurence, Munnich, Arnold, Lyonnet, Stanislas, Bonnefont, Jean-Paul, Portes, Vincent Des, Amiel, Jeanne
• Format: Article
• Language: English
• Subjects: exome sequencing; Female; Genetic Diseases, X-Linked - genetics; Humans; Intellectual Disability - genetics; Male; Pedigree; Ribosomal Proteins - genetics; RPL10; syndromic X-linked intellectual disability
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.37094

Intellectual disability is a neurodevelopmental disorder of impaired adaptive skills and low intelligence quotient. The overall prevalence is estimated at 2–3% in the general population with extreme clinical and genetic heterogeneity, and it has been associated with possibly causative mutations in more than 700 identified genes. In a recent review, among over 100 X‐linked intellectual disability causative genes, eight were reported as “awaiting replication.” Exome sequencing in a large family identified a missense mutation in RPL10 highly suggestive of X‐linked intellectual disability. Herein, we report on the clinical description of four affected males. All patients presented apparent intellectual disability (4/4), psychomotor delay (4/4) with syndromic features including amniotic fluid excess (3/4), microcephaly (2/4), urogenital anomalies (3/4), cerebellar syndrome (2/4), and facial dysmorphism. In the literature, two mutations were reported in three families with affected males presenting with autism. This report confirms the implication of RPL10 mutations in neurodevelopmental disorders and extends the associated clinical spectrum from autism to syndromic intellectual disability. © 2015 Wiley Periodicals, Inc.