Kizhakkedath Praseetha, AlDhaheri Watfa, Baydoun Ibrahim, Tabouni Mohammed, John Anne, Almansoori Taleb M, Al-Turki Saeed, Al-Jasmi Fatma, Alblooshi Hiba
Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Department of Pediatrics, Tawam Hospital, Al Ain, United Arab Emirates.
Front Genet. 2023 Jul 27;14:1219514. doi: 10.3389/fgene.2023.1219514. eCollection 2023.
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.
伯克 - 兰道 - 佩雷斯综合征（BILAPES）是一种常染色体隐性遗传的脑肾综合征，与该基因的遗传缺陷相关，于2017年首次报道于一个大型贝都因家族的6名成员中。该基因编码一种假定的线粒体锌转运体，其表达广泛，在脑、肾和骨骼肌中表达量最高。自首次报道以来，仅描述了另外1例受影响患者，但在贝都因家族和该第二名患者的疾病临床表现之间存在一些不一致之处，如听力损失、生长发育迟缓以及神经影像学表现。在此，我们报告了来自一个中东近亲家族的另外2例患者，他们具有慢性肾病、神经发育倒退、共济失调、听力损失和眼部异常等特征，这些特征在很大程度上与BILAPES一致。全外显子测序在该基因中检测到一个纯合的框内缺失c.1049_1051delCAG（p.Ala350del），这与原始文献报道中的患者所检测到的变异相同，且该变异在家族中与疾病共分离。然而，在此处描述的患者中，脑部MRI显示小脑萎缩，这并非原始报道中该综合征的主要特征。我们的研究结果为与该基因相关的BILAPES提供了进一步证据，并有助于明确临床谱。
