Genetic testing and molecular biomarkers · 2026
Expanding the Phenotypic Spectrum of Trafficking Protein Particle Complex Subunit 9-Related Intellectual Developmental Disorder: Prader-Willi-like Presentation in a Tunisian Family.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Ben Jemaa Maha, El Mabrouk Haifa, Mahfood Mona, Kraawa Ichraf, Rouissi Aida, Turki Ilhem, Gribaa Moez, Najar Salma, Tlili Abdelaziz, Hmida Dorra
Аннотация
BACKGROUND: Intellectual Disability-Obesity-Brain Malformations-Facial Dysmorphism Syndrome (IDOB-FMD) is a rare genetic disorder characterized by moderate to severe intellectual disability, microcephaly, and brain abnormalities such as a thin corpus callosum, cerebellar hypoplasia, and cerebral white matter hypoplasia, often observed on MRI scans. Additional features include obesity and craniofacial dysmorphism. IDOB-FMD is inherited in an autosomal recessive manner, attributed to Trafficking Protein Particle Complex Subunit 9 (TRAPPC9) deficiency, with a prevalence of less than 1 in 1,000,000. This syndrome shares clinical similarities with Prader-Willi syndrome (PWS).
RESULTS: In our study, we conducted a clinical evaluation of two Tunisian siblings suspected of having Prader-Willi-like syndrome (PWLS) based on their clinical presentation. Whole-exome sequencing (WES) was employed to identify genetic variants associated with the phenotype. Variant interpretation and segregation analysis were performed to ascertain the pathogenicity of the identified variants. WES revealed a homozygous mutation in the TRAPPC9 gene in both siblings. The variant was predicted to be pathogenic and segregated with the phenotype within the family. Clinical examination was consistent with PWLS, including intellectual disability, microcephaly, and dysmorphism.
CONCLUSIONS: Our findings emphasize the importance of genetic testing in patients presenting with PWLS features, highlighting a TRAPPC9 mutation that expands the known mutational spectrum. This study, the second investigation of PWLS in Tunisia, reports a pathogenic variant in the TRAPPC9 gene underlying the observed phenotype in this family, offering valuable insights into clinical management and genetic counseling. Our identification of this variant not only reveals genetic heterogeneity but also prompts further research to elucidate the genotype-phenotype correlations and molecular mechanisms underlying TRAPPC9-related disorders.
RESULTS: In our study, we conducted a clinical evaluation of two Tunisian siblings suspected of having Prader-Willi-like syndrome (PWLS) based on their clinical presentation. Whole-exome sequencing (WES) was employed to identify genetic variants associated with the phenotype. Variant interpretation and segregation analysis were performed to ascertain the pathogenicity of the identified variants. WES revealed a homozygous mutation in the TRAPPC9 gene in both siblings. The variant was predicted to be pathogenic and segregated with the phenotype within the family. Clinical examination was consistent with PWLS, including intellectual disability, microcephaly, and dysmorphism.
CONCLUSIONS: Our findings emphasize the importance of genetic testing in patients presenting with PWLS features, highlighting a TRAPPC9 mutation that expands the known mutational spectrum. This study, the second investigation of PWLS in Tunisia, reports a pathogenic variant in the TRAPPC9 gene underlying the observed phenotype in this family, offering valuable insights into clinical management and genetic counseling. Our identification of this variant not only reveals genetic heterogeneity but also prompts further research to elucidate the genotype-phenotype correlations and molecular mechanisms underlying TRAPPC9-related disorders.