Louisa Sanchez 1, Evelyn Douglas1, Linda Burrows1, Kathy Cox1, Maely Gauthier2, Karin Kassahn2, Sam Crafter3, Lesley McGregor4, Chris Barnett4, Kathie Friend1.
1 Molecular Genetics Unit, SA Pathology, North Adelaide, South Australia
2 Technology Advancement Unit, SA Pathology, Adelaide, South Australia
3 Dept. of Nephrology, Women’s and Children’s Hospital, North Adelaide, South Australia
4 South Australian Clinical Genetics Service, SA Pathology, North Adelaide, South Australia
Alport syndrome (ATS) is a disorder of the basement membrane characterised by glomerulonephropathy, resulting in renal failure, as well as sensorineural hearing loss and ocular anomalies. The majority of cases are X-linked, associated with variants in the COL4A5 gene, including a large number of multi exon deletions and duplications. Autosomal recessive and autosomal dominant forms are associated with variants in the COL4A3 and COL4A4 genes. Rarely patients with ATS also have diffuse leiomyomatosis (ATS-DL), a benign neoplastic condition characterised by aberrant proliferation of well differentiated smooth muscle cells, involving the gastrointestinal, tracheobronchial and female genital tracts. A contiguous deletion of the 5’ exons of COL4A5 and COL4A6 is commonly detected in patients with this phenotype.
Our laboratory (Genetics and Molecular Pathology, SA Pathology) has recently introduced screening of genes known to be involved in Alport syndrome using multiplex ligation-dependent probe amplification (MLPA – MRC Holland), in combination with Next Generation Sequencing using the Illumina TruSight One and NextSeq platform. Of the 20 cases completed to date, 3 patients have variants detected by MLPA, and a further 11 patients have reportable variants identified by NGS. No variants of clinical significance were identified in the remaining 6 patients.
Louisa is a medical scientist working in the Molecular Genetics Unit at SA Pathology in Adelaide, South Australia.