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.

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Journal Journal of Human Genetics
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Hollink, I.H.I.M, Alfadhel, M, Al-Wakeel, A.S, Ababneh, F, Pfundt, R, de Man, S.A, … van de Laar, I.M.B.H. (2016). Broadening the phenotypic spectrum of pathogenic LARP7 variants: Two cases with intellectual disability, variable growth retardation and distinct facial features. Journal of Human Genetics, 61(3), 229–233. doi:10.1038/jhg.2015.134