A comprehensive clinical and genetic study in 127 patients with ID in Kinshasa, DR Congo

Abstract

Pathogenic variants account for 4 to 41% of patients with intellectual disability (ID) or developmental delay (DD). In Sub-Saharan Africa, the prevalence of ID is thought to be higher, but data in Central Africa are limited to some case reports. In addition, clinical descriptions of some syndromes are not available for this population. This study aimed at providing an estimate for the fraction of ID/DD for which an underlying etiological genetic cause may be elucidated and provide insights into their clinical presentation in special institutions in a Central African country. A total of 127 patients (33 females and 94 males, mean age 10.03 ± 4.68 years), were recruited from six institutions across Kinshasa. A clinical diagnosis was achieved in 44 but molecular confirmation was achieved in 21 of the 22 patients with expected genetic defect (95% clinical sensitivity). Identified diseases included Down syndrome (15%), submicroscopic copy number variants (9%), aminoacylase deficiency (0.8%), Partington syndrome in one patient (0.8%) and his similarly affected brother, X-linked syndromic Mental Retardation type 33 (0.8%), and two conditions without clear underlying molecular genetic etiologies (Oculo-Auriculo-Vertebral and Amniotic Bands Sequence). We have shown that genetic etiologies, similar to those reported in Caucasian subjects, are a common etiologic cause of ID in African patients from Africa. We have confirmed the diagnostic utility of clinical characterization prior to genetic testing. Finally, our clinical descriptions provide insights into the presentation of these genetic diseases in African patients.

Centers for Mendelian Genomics: A decade of facilitating gene discovery

“…Many of the CMG discoveries are still in the process of gathering cases, functional data, or going through the peer review publication process. 26 South Africa, Kenya, Egypt, 27,28 Iraq, 29 Chile 30,31 , Turkey, [32][33][34] and Lithuania. For some, this has involved training opportunities within a CMG-affiliated laboratory, while for others learning happened through collaborative meetings to discuss analysis results on teleconferences.…”

“…A special week-long Genomics course is incorporated into the medical school curriculum at Johns Hopkins and will be developed into an on-line training module. The CMGs have enabled researchers and clinicians investigating rare Mendelian diseases in the US and around the world to access gene discovery techniques, including those in countries where access to research opportunities is limited, such as the Democratic Republic of the Congo, 26 South Africa, Kenya, Egypt, 27, 28 Iraq, 29 Chile 30, 31 , Turkey, 32–34 and Lithuania. For some, this has involved training opportunities within a CMG-affiliated laboratory, while for others learning happened through collaborative meetings to discuss analysis results on teleconferences.…”

Centers for Mendelian Genomics: A decade of facilitating gene discovery

“…The CMGs provided educational and networking opportunities by hosting in-person courses attended by over 300 analysts and researchers, including the Mendelian Data Analysis Workshop (University of Washington), Interpreting Genomes for Rare Disease (Broad), and McKusick Short Course in Human and Mammalian Genetics (Baylor-Hopkins). The CMGs have enabled researchers and clinicians investigating rare Mendelian diseases around the world to access gene discovery techniques, including those in countries where access to research opportunities is limited, such as the Democratic Republic of the Congo, 27 South Africa, Kenya, Egypt, 28,29 Iraq, 30 Chile, 31,32 Turkey, [33][34][35] and Lithuania. For some, this has involved training opportunities within a CMG-affiliated laboratory, whereas for others, learning happened through collaborative meetings to discuss analysis results on teleconferences.…”

Clinical presentation and evolution of Xia‐Gibbs syndrome due to p.Gly375ArgfsTer3 variant in a patient from DR Congo (Central Africa)

“…At the age of 8 years a blood sample was obtained and DNA extraction was performed at the Center for Human Genetics of the University of Kinshasa (DR Congo) and patient‐only Exome Sequencing (ES) testing at the Baylor College of Medicine (Texas, The United States) through the Baylor Hopkins Center for Mendelian Genomics (BHCMG). Library preparation, sequencing platform and bioinformatic analysis were as previously described (Lumaka et al, 2018).…”