This study presents the clinical phenotype and genetic variant data of a family with craniofacial microsomia. The proband was a neonate with facial abnormalities and a rare feature of airway obstruction. Genetic analyses indicated a heterozygous SF3B2 variant, which was inherited from the father. A Minigene assay revealed that two mRNA products were produced, leading to a premature termination codon.

We described the first published case of familial cardiac-urogenital syndrome indicating gonadal mosaicism.

We assessed the additional diagnostic yield from candidate and new disease genes as well as from trio-WGS in a previously described cohort of 63 index patients with developmental or epileptic encephalopathies. Out of 20 patients that remained undiagnosed and without strong candidate gene after WES and CMA, four pathogenic variants (20%) were found by trio-WGS, which, however, could have all been detected in a WES conducted with today's methods and knowledge. Therefore, the added value of WGS today is still limited and mainly consists in a more reliably detection of copy number variants and its notwithstanding potential for detection of structural and noncoding variants.

We reported a child with profound bilateral non-syndromic sensorineural hearing and compound heterozygosity for a common nonsense and novel deep intronic variant that was identified by WGS. The results of genetic testing provided precise genetic counseling and prenatal diagnosis for this family and was contributed to diagnose other USH1F patients in the future. Our findings highlight the power of WGS for detecting deep-intronic variants in patients with undiagnosed rare diseases. Additionally, this case expands the variant spectrum of the PCDH15 gene, and our results support the extremely low carrier frequency of c.733C>T in the Chinese population.

We present a male who presented with post-axial polydactyly of all four limbs, a significantly small chest with a pectus excavatum and anterior flaring of the ribs. Clinical genetic testing revealed a likely pathogenic frameshift variant and an intronic variant of uncertain significance (VUS) in DYNC2H1. RNA sequencing (RNA-Seq) was essential in variant interpretation and as a result of these data, the intronic VUS was able to be reclassified as likely pathogenic by ACMG criteria, thus confirming the diagnosis of short-rib thoracic dysplasia 3 in our patient and opening the door to prenatal testing for the parents' future pregnancies.

This study assesses the degree of genetic substructure in the Lebanese population, which is known to have high rates of endogamy and consanguinity. F parameters were analyzed to assess degree of coancestry and provide local/regional laboratories with data that can help minimize misinterpretations of DNA forensic and kinship cases.