Maternal UPD of chromosome 7 in a patient with Silver-Russell syndrome and Pendred syndrome

Background: Silver-Russell syndrome (SRS) is a heterogeneous imprinting disorder featuring severe intrauterine and postnatal growth retardation and dysmorphic features. Pendred syndrome (PDS) is an autosomal recessive disorder caused by mutations in the SLC26A4 gene characterized by sensorineural hearing loss. Methods: Karyotyping analysis was performed to investigate any chromosomal abnormalities. Whole-genome copy number variation and loss of heterozygosity were analyzed using an Affymetrix CytoScan 750 K Microarray. Variant screening was performed by targeted next-generation sequencing on all known deafness-causing genes. Results: The proband was a patient with SRS caused by maternal uniparental disomy 7. The PDS of the proband was caused by homozygous variant c.919-2A ' G of SLC26A4; both mutated alleles were inherited from his mother. Conclusion: This is the first report of uniparental disomy 7 leading to SRS and Pendred syndrome. Patients with intrauterine growth retardation or those born small for gestational age and exhibiting postnatal growth failure should undergo molecular testing to reach a clinical diagnosis.