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Pedigree of 3 families with AS. XL-AS, X-linked Alport syndrome; LP, likely pathogenic; AD-AS, autosomal dominant Alport syndrome; VUS, uncertain significance; AR-AS, autosomal recessive Alport syndrome; P, pathogenic.
Source publication
Background:
At least 10% of adults and most of the children who receive renal replacement therapy have inherited kidney diseases. These disorders substantially decrease their life quality and have a large effect on the health-care system. Multisystem complications, with typical challenges for rare disorders, including variable phenotypes and fragm...
Citations
... Inherited kidney diseases (IKDs) are a group of kidney diseases characterized by abnormal kidney structure or function caused by genetic factors which present substantial clinical heterogeneity in clinical presentation, age of onset, severity, and progression of symptoms, accounting for at least 10%-15% of cases of kidney replacement therapy (Zhang et al., 2021;Torra et al., 2021). So far, there have been more than 150 known IKDs which can be divided into two categories of inherited renal structural abnormality and inherited renal dysfunction (Devuyst et al., 2014;Cunha et al., 2020). ...
Background: Inherited kidney diseases (IKDs) are a group of kidney diseases characterized by abnormal kidney structure or function caused by genetic factors, but they are not easily diagnosed in childhood due to either nonspecific symptoms and signs or clinically silent symptoms in the early stages until the progressive stages, even end-stages. Early diagnosis of IKDs is very urgent for timely treatment and improving outcomes of patients. So far, the etiological diagnosis has been accelerated with the advance of clinical genetic technology, particularly the advent of next-generation sequencing (NGS) that is not only a powerful tool for prompt and accurate diagnosis of IKDs but also gives therapy guidance to decrease the risk of unnecessary and harmful interventions.
Methods: The patients presenting with urinalysis abnormalities or structural abnormalities from 149 Chinese families were enrolled in this study. The clinical features of the patients were collected, and the potentially causative gene variants were detected using exome sequencing. The clinical diagnostic utility of the genetic testing was assessed after more detailed clinical data were analyzed.
Result: In total, 55 patients identified having causative variants by exome sequencing were genetically diagnosed, encompassing 16 (29.1%) autosomal dominant IKDs, 16 (29.1%) autosomal recessive IKDs, and 23 (41.8%) X-linked IKDs, with 25 unreported and 45 reported variants. The diagnostic yield was 36.9%. The utility of the exome sequencing was accessed, 12 patients (21.8%) were confirmed to have suspected IKDs, 26 patients (47.3%) discerned the specific sub-types of clinical category, and 17 patients (30.9%) with unknown etiology or lack of typical manifestations were reclassified.
Conclusion: Our study supported that genetic testing plays a crucial role in the early diagnosis for children with IKDs, which affected follow-up treatment and prognostic assessment in clinical practice. Moreover, the variant spectrum associated with IKDs was expanded.
... GLA gene mutation will lead to the deficiency of the alphagalactosidase A (α-Gal A) enzyme. The most frequent GLA mutations are missense followed by nonsense mutations, but also deletions, duplication, insertions, frameshift, and splice-site mutations are observed (11,21). ...
Inherited renal diseases represent 20% of the causes of end-stage renal diseases. Fabry disease, an X-linked lysosomal storage disorder, results from α-galactosidase A deficient or absent activity followed by globotriaosylceramide (Gb3) accumulation and multiorgan involvement. In Fabry disease, kidney involvement starts early, during intrauterine life by the Gb3 deposition. Even if chronic kidney disease (CKD) is discovered later in adult life in Fabry disease patients, a decline in glomerular filtration rate (GFR) can occur during adolescence. The first clinical sign of kidney involvement is represented by albuminuria. So, early and close monitoring of kidneys function is required: albuminuria and proteinuria, urinary albumin-to-creatinine ratio, serum creatinine, or cystatin C to estimate GFR, while urinary sediment with phase-contrast microscopy under polarized light may be useful in those cases where leucocyte α-Gal A activity and GLA genotyping are not available. Children with Fabry disease and kidney involvement should receive enzyme replacement therapy and nephroprotective drugs (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) to prevent or slow the progressive loss of kidney functions. Early diagnosis of Fabry disease is important as enzyme replacement therapy reduces symptoms, improves clinical features and biochemical markers, and the quality of life. More importantly, early treatment could slow or stop progressive organ damage in later life.
