Case report: Birk-Landau-Perez syndrome linked to the SLC30A9 gene-identification of additional cases and expansion of the phenotypic spectrum

• Published in: Frontiers in genetics Vol. 14; p. 1219514
• Main Authors: Kizhakkedath, Praseetha, AlDhaheri, Watfa, Baydoun, Ibrahim, Tabouni, Mohammed, John, Anne, Almansoori, Taleb M, Al-Turki, Saeed, Al-Jasmi, Fatma, Alblooshi, Hiba
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 27-07-2023
• Subjects: ataxia; developmental regression; Genetics; hyperechogenic kidneys; oculomotor apraxia; tubulointerstitial nephritis; zinc transporter; hyperechogenic kidneys; ataxia; tubulointerstitial nephritis; BILAPES; developmental regression; zinc transporter; oculomotor apraxia
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2023.1219514

Birk-Landau-Perez syndrome (BILAPES) is an autosomal recessive cerebro-renal syndrome associated with genetic defects in the
gene, initially reported in 2017 in six individuals belonging to a large Bedouin kindred. The
gene encodes a putative mitochondrial zinc transporter with ubiquitous expression, the highest found in the brain, kidney, and skeletal muscle. Since the first report, only one additional affected patient has been described, but there were some inconsistencies, such as hearing loss, failure to thrive, and neuroimaging findings between the clinical presentation of the disease in the Bedouin family and the second patient. Here, we present two more patients from a consanguineous Middle Eastern family with features of chronic kidney disease, neurodevelopmental regression, ataxia, hearing loss, and eye abnormalities, which were largely consistent with BILAPES. Whole-exome sequencing detected a homozygous in-frame deletion c.1049_1051delCAG (p.Ala350del) in the
gene, which was the same variant detected in the patients from the primary literature report and the variant segregated with disease in the family. However, in the patients described here, brain MRI showed cerebellar atrophy, which was not a cardinal feature of the syndrome from the primary report. Our findings provide further evidence for
-associated BILAPES and contribute to defining the clinical spectrum.