TY - JOUR
T1 - Case report
T2 - Birk–Landau–Perez syndrome linked to the SLC30A9 gene—identification of additional cases and expansion of the phenotypic spectrum
AU - Kizhakkedath, Praseetha
AU - AlDhaheri, Watfa
AU - Baydoun, Ibrahim
AU - Tabouni, Mohammed
AU - John, Anne
AU - Almansoori, Taleb M.
AU - Al-Turki, Saeed
AU - Al-Jasmi, Fatma
AU - Alblooshi, Hiba
N1 - Publisher Copyright:
Copyright © 2023 Kizhakkedath, AlDhaheri, Baydoun, Tabouni, John, Almansoori, Al-Turki, Al-Jasmi and Alblooshi.
PY - 2023
Y1 - 2023
N2 - Birk–Landau–Perez syndrome (BILAPES) is an autosomal recessive cerebro-renal syndrome associated with genetic defects in the SLC30A9 gene, initially reported in 2017 in six individuals belonging to a large Bedouin kindred. The SLC30A9 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 SLC30A9 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 SLC30A9-associated BILAPES and contribute to defining the clinical spectrum.
AB - Birk–Landau–Perez syndrome (BILAPES) is an autosomal recessive cerebro-renal syndrome associated with genetic defects in the SLC30A9 gene, initially reported in 2017 in six individuals belonging to a large Bedouin kindred. The SLC30A9 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 SLC30A9 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 SLC30A9-associated BILAPES and contribute to defining the clinical spectrum.
KW - BILAPES
KW - ataxia
KW - developmental regression
KW - hyperechogenic kidneys
KW - oculomotor apraxia
KW - tubulointerstitial nephritis
KW - zinc transporter
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U2 - 10.3389/fgene.2023.1219514
DO - 10.3389/fgene.2023.1219514
M3 - Article
AN - SCOPUS:85167580598
SN - 1664-8021
VL - 14
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 1219514
ER -