Akademik Veri Yönetim Sistemi
14th Balkan Congress of Human Genetics & 9th Rare Disease SEE Meeting 2023, Skopje, Makedonya, 5 - 07 Ekim 2023, ss.70, (Özet Bildiri)
A CASE REPORT OF DONNAI BARROW
SYNDROME: FIRST GROSS DELETION MUTATION IN LRP2 GENE
Betül
Kesriklioğlu, Beyza Karaca Doğan, Esra Arslan Ateş, Sinem Fırtına
Department
of Medical Genetics, Cerrahpasa Medical Faculty, Istanbul University -
Cerrahpasa, Istanbul, Turkey
Donnai-Barrow
Syndrome (DBS)/ Facioculoacousticorenal (FOAR) Syndrome is a multiple
congenital malformation syndrome characterized by typical facial dysmorphism,
ocular findings, hearing loss, agenesis of the corpus callosum,
low-molecular-weight proteinuria and variable intellectual disability. DBS is
an autosomal recessive disorder caused by loss of function variants in the LRP2
(low-density lipoprotein receptor-related protein 2) gene (2q31.1) encoding the
protein megalin, an endocytic transmembrane glycoprotein. We present a case
with a deletion in exons 17-19 of the LRP2 gene with optic disc hypoplasia,
pigmentary retinopathy, corpus callosum hypoplasia, developmental delay, growth
retardation, hypothroidism, bilateral hypoplastic kidney and proteinuria in
addition to dysmorphic findings compatible with DBS. We performed whole exome
sequencing (WES), karyotype and microarray analysis for diagnosis and validated
the exon 17-19 deletion with PCR. Karyotype and microarray analysis from
peripheral blood were normal. No reads were observed between exons 17 and 19 of
the LRP2 gene in WES analysis. These exons could not be amplified with PCR.
Then, we amplified exon 16-20 with long PCR from cDNA samples of the patients
and the parents for validation. We observed deletion in exon 17-19 region in
patient’s sample when loaded into the gel electrophoresis.
Small
deletions or insertions causing frameshifts, as well as conserved splice site,
nonsense and missense mutations of LRP2 gene in DBS/FOAR families were reported
before. We report the first case of gross deletion in LRP2 in a patient
clinically diagnosed with DBS.
Keywords:
Donnai Barrow Syndrome, LRP2 gene, Gross deletion, Whole exome sequencing, Gel
electrophoresis