TRAPPC9-Related Intellectual Disability: Report of Two New Cases and Review of the Literature

Abstract

<b><i>Introduction:</i></b> Hereditary forms of intellectual disability (ID), an estimated prevalence ranging between 1% and 3% in the general population, are among the most important problems in health care. Especially, autosomal-recessive ID has a very heterogeneous molecular basis and a lack of specific phenotypic features. <b><i>Methods:</i></b> Here, we report on two unrelated patients with autosomal-recessive ID, microcephaly, and autistic features and review the patients with TRAPPC9-related ID. Whole-exome sequencing and array CGH were performed for molecular diagnosis of the patients. <b><i>Results:</i></b> The first case has a microdeletion on chromosome 8q24.23-q24.3 region which is 1.7 Mb in length and includes the last 5 exons of <i>TRAPPC9</i>, and c.3435delG [p.Thr1146Profs*8] deletion. The second case has a homozygous missense c.623A>C (p.His208Pro) variant in <i>TRAPPC9</i> which is detected by means of whole-exome sequencing study of the proband. We also reviewed the clinical findings and mutation spectrum of all patients with TRAPPC9-related ID reported so far. <b><i>Conclusions:</i></b> Our study showed that the most consistent clinical findings for TRAPPC9-related ID are ID, microcephaly, and some structural brain MRI abnormalities. The mutations in the <i>TRAPPC9</i> are scattered throughout all exons of <i>TRAPPC9</i> indicating there is no hot spot mutation region in this gene.