Introduction Mucopolysaccharidoses (MPS) are lysosomal storage disorders characterized by distinctive dysmorphic features and skeletal abnormalities, with marked genetic heterogeneity across populations. Limited data exist on the MPS clinical spectrum and molecular characteristics in North Africa. Methods We conducted a retrospective study of 24 MPS patients followed at Mohammed V Military Hospital, Rabat, Morocco (2005–2023). Clinical phenotyping utilized Human Phenotype Ontology terminology. Biochemical analyses included urinary glycosaminoglycans and enzymatic assays. Molecular analysis comprised DNA sequencing of relevant genes. Results MPS I predominated (75%, n = 18), followed by MPS IV (17%, n = 4), and MPS III and VII (4% each). The consanguinity rate was 78% (first-degree: 72%). All 16 genotyped MPS I patients carried the homozygous p.P533R (c.1598C>G) mutation (100%), confirming a founder effect. Despite genetic homogeneity, phenotypic variability was observed: Hurler-Scheie intermediate phenotype (83.3%) versus severe Hurler (16.7%). Common features included coarse facial features (HP:0000280, 89%), dysostosis multiplex (HP:0000925, 94%), joint contractures (HP:0001371, 94%), hepatosplenomegaly (78%), and corneal opacity (HP:0007957, 100%). The median age at diagnosis was 4.0 years (range 1 month–13.5 years), with a median diagnostic delay of 3.0 years. Conclusion This first comprehensive Moroccan MPS series establishes p.P533R as a major founder mutation in MPS I, with implications for targeted genetic testing and counseling in consanguineous North African populations. The phenotypic variability despite complete genetic homogeneity suggests modifier genes influence disease expression.
Objective To conduct a pilot study to assess whether saliency-based explainable artificial intelligence (XAI) affects the recognition of genetic conditions from facial images. Methods Forty-four medical geneticists, divided into AI-only and XAI-supported groups, assessed 18 images of individuals with or without genetic conditions. Diagnostic accuracy and confidence were recorded before and after viewing an AI classifier’s prediction probability, with or without XAI explanations. Mediation analyses were conducted to better interpret how geneticists interact with AI and XAI in decision-making. Results AI-only and XAI support improved accuracy for correct AI classifications, while incorrect AI classifications decreased accuracy. Average confidence increased with correct and decreased with incorrect classification. Geneticists reported that AI prediction probability was useful, whereas XAI explanations were viewed less favorably. For incorrect AI classifications, there was a negative correlation between accuracy improvement and perceived AI usefulness. When AI was correct (without XAI), the model prediction probability acted as a mediator between user confidence and the user’s decision to choose the same answer as AI. Conclusion The lack of accuracy or confidence improvements indicates that participants did not integrate saliency-based XAI into decisions. AI prediction probability had a greater impact on participants’ decision-making. These data may help inform larger studies.
OBJECTIVE:To describe prenatal evaluation and postnatal outcome of monochorionic diamniotic twins with discordant anomalies and genetic findings after intracytoplasmic sperm injection and double-embryo transfer. METHODS:A 36-year-old gravida 3 para 0 woman conceived after transfer of two blastocysts. Ultrasound identified monochorionic diamniotic twins and a liver-containing omphalocele in fetus B. Both sacs underwent separate amniocentesis. Testing included karyotyping, chromosome microarray, Beckwith-Wiedemann syndrome analysis, trio whole-exome sequencing, short tandem repeat analysis, postnatal peripheral blood fluorescence in situ hybridization, and placental histopathology. RESULTS:Fetus A had mosaic 45,X[9]/46,XY[91]; fetus B had a 46,XY karyotype. Other prenatal genetic tests were unremarkable. Discordance at 11 of 21 short tandem repeat loci supported dizygosity. Following prelabor rupture of membranes at 34 + 5 weeks, two male infants were delivered by cesarean section. Twin A had hypospadias and bilateral cryptorchidism; twin B had giant omphalocele requiring surgical repair. Postnatal fluorescence in situ hybridization detected no sex-chromosome mosaicism. Placental histopathology confirmed monochorionicity. CONCLUSION:Monochorionicity does not exclude dizygosity after assisted reproduction. Separate sampling of both sacs may inform discordant cases, and prenatal-postnatal discrepancies in 45,X/46,XY mosaicism warrant cautious longitudinal interpretation.
