Background Renal–hepatic–pancreatic dysplasia type 1 (RHPD1) is a rare sporadic and autosomal recessive disorder with unknown incidence. RHPD1 is caused by biallelic pathogenic variants in NPHP3, which encode nephrocystin, an important component of the ciliary protein complex. Case presentation In this case report, we describe a male newborn who was confirmed by ultrasound to have renal enlargement with multiple cysts, pancreatic enlargement with cysts, and increased liver echogenicity, leading to the clinical diagnosis of RHPD. In addition, a compound heterozygous pathogenic variant, namely, NPHP3 c.1761G > A (p. W587*) and the c.69delC (p. Gly24Ala24*11) variant, was detected by WES. The patient was clinically and genetically diagnosed with RHPD1. At 34 h of life, the infant died of respiratory insufficiency. Conclusion This is the first published case of RHPD1 in China. This study broadens the known range of RHPD1 due to NPHP3 pathogenic variants.

Background: MECP2 duplication syndrome (MDS), a rare X-linked genomic disorder affecting predominantly males, characterized by delayed or absent speech development, severe motor and cognitive impairment and recurrent respiratory infections, is caused by duplication of the chromosomal region located on chromosome Xq28, containing the methyl CpG binding protein-2 (MECP2) gene. MECP2 acts as a transcriptional repressor or activator regulating genes related to nervous system development. The objective of the study adds a clinical description of MDS to include imaging changes consistent with during the fetal period to the neonatal period. Methods: Conventional G-banding was used to analyze chromosome karyotypes of all pedigree tested. Then, High- throughput sequencing technology, advanced biological information analysis and site validation and pedigree validation were verified by Sanger sequencing. Results: Chromosome karyotype analysis revealed that one male patient had a chromosome karyotype 46, Y, dup (X) (q27.2q28), High- throughput sequencing technology showed an Xq27.1q28 duplication, with spanned 14.45Mb, duplication encompassed the MECP2 gene. Both the mother and grandmother had karyotype 46, X, dup (X) (q27.2q28), CNV-seq(copy number variation sequencing）analysis of their family members confirmed that they had carried similar duplications, with spanned 15.188Mb, as female carriers of the MECP2 duplication. While the father and uncle of the family members do not carry this area duplication. Sanger validation result was consistent with the CNV-seq analysis. Conclusion: In this study, a case of developmental delay and recurrent respiratory tract infections as the main symptoms, suspected of MECP2 duplication syndrome male child genetic analysis, clear its causes, explore the correlation of genotype and phenotype, more accurately describe the complete clinical spectrum of MDS, provide the basis for prenatal diagnosis and genetic counselling of familial female carriers.