Among 158 distinct variants, 80 (50.6%) were previously unreported, confirming broad allelic heterogeneity. Eleven patients showed more than one variant. Segregation analysis indicated biallelic disease in five patients, digenic in one, de novo variant with unknown phase in two. Furthermore, our NGS protocol allowed the identification of two patients with somatic mosaicism, which was undetectable with Sanger sequencing. Among patients without PKD1/PKD2 variants, we identified three with possible alternative diagnosis: a patient with biallelic mutations in PKHD1, confirming the overlap between recessive and dominant PKD, and two patients with variants in ALG8 and PRKCSH, respectively. Genotype-phenotype correlations showed that patients with PKD1 variants predicted to truncate (T) the protein experienced end-stage renal disease 9 years earlier than patients with PKD1 non-truncating (NT) mutations and >13 years earlier than patients with PKD2 mutations. ADPKD-PKD1 T cases showed a disease onset significantly earlier than ADPKD-PKD1 NT and ADPK-PKD2, as well as a significant earlier diagnosis. These data emphasize the need to combine clinical information with genetic data to achieve useful prognostic predictions.

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We describe a boy with autism spectrum disorder and intellectual disability who presented a de novo interstitial deletion of the long arm of chromosome 4 (4q13.2q21.1), sized approximately 7.5 Mb, identified by array-based comparative genomic hybridization (array-CGH), considered as pathogenic and not described in the literature so far. The phenotype of this child was basically dominated by a severe neurodevelopmental impairment without particular dysmorphisms suggesting a specific genetic diagnosis at first. This case report once again underlines the importance of a genetic screening by array-CGH in individuals with autism spectrum disorder, in particular when associated with intellectual disability, even if no specific dysmorphisms are present.