CCDC47 gene and trichohepatoneurodevelopmental syndrome: Report of the fifth and sixth cases from Saudi Arabia

Abstract

AbstractTrichohepatoneurodevelopmental syndrome (THNS) is an ultra‐rare and complex disorder affecting multiple organ systems. It is characterized by liver dysfunction, hypotonia, global developmental delay, coarse hair, and dysmorphic features. We describe two cases of THNS of Saudi origin, the fifth and sixth cases in the medical literature. Both cases presented with multiple dysmorphic features, generalized hypotonia, global developmental delay, and high liver enzyme level. Exome sequencing of Case 1 identified a pathogenic homozygous variant within the CCDC47: NM_020198.2:c.567_570del, p.(Glu190Profs*7). Genome sequencing of Case 2 identified two likely pathogenic heterozygous variants within the CCDC47: NM_020198.2:c.1327C>T, p.(Arg443*) and NM_020198.2:c.422dup, p.(Leu141Phefs*19). The trans phase of the detected variants has been confirmed by the parental testing. Furthermore, we evaluated the gene–disease association as per ClinGen guidelines and reached a strong level of association after inclusion of the new patients/variants. The findings from these cases will help to delineate the clinical phenotype and the mutational spectrum of this complex disorder.