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Renal and urinary tract diseases
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
This type of haematuria, usually recurrent and painless, sometimes gross or microscopic, is not associated with deafness, ocular defect, hypertension or renal impairment. Moderate basement membrane thinning is sometimes found. Transmission is usually consistent with autosomal dominant inheritance when analysis is performed on all available family members. A molecular defect in either of the type IV collagen genes on chromosome 2q (COL4A4 or COL4A3) is often responsible.
Genetics in Otology and Neurotology
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Progressive sensorineural hearing loss, renal disorder (glomerulonephritis, haematuria, renal failure) and eye problems (lenticular and macular abnormalities) are observed. Almost 50% develop progressive bilateral hearing loss, which usually begins in the second decade.30 This syndrome is X-linked in 85%, autosomal recessive in 15% and autosomal dominant in the remainders. In the X-linked form, males are more severely affected than females. The COL4A5 gene on Xq22 and the COL4A3 and COL4A4 genes on chromosome 2q36–q37 are responsible for the syndrome.30
The role of discoidin domain receptor 2 in the renal dysfunction of alport syndrome mouse model
Published in Renal Failure, 2021
Yuya Sannomiya, Shota Kaseda, Misato Kamura, Hiroshi Yamamoto, Hiroyuki Yamada, Masataka Inamoto, Jun Kuwazuru, Saki Niino, Tsuyoshi Shuto, Mary Ann Suico, Hirofumi Kai
Alport syndrome (AS) is a hereditary disease that causes progressive loss of kidney function. It is caused by a mutation in one of the type IV collagen genes that code for COL4A3, COL4A4, and COL4A5 proteins. These type IV collagens form protomer network that are important components of the glomerular basement membrane (GBM). Mutations in type IV collagen genes disrupt the structure and function of GBM [1,2]. Abnormal GBM structure interferes with the glomerular filtration system leading to proteinuria, inflammation, renal fibrosis and finally to end-stage renal disease (ESRD). Currently, renin angiotensin aldosterone system (RAAS) inhibitors are used for AS therapy. Although early treatment with RAAS inhibitor delays renal failure in AS patients, the disease eventually progresses into ESRD [3,4]. It is now generally believed that RAAS inhibitor is not sufficient for AS therapy. Therefore, it is important to continue the search for novel therapeutic targets that have different mechanism from RAAS inhibitors.
An update on current and potential genetic insights and diagnosis of Alport syndrome
Published in Expert Opinion on Orphan Drugs, 2020
The ultimate protein product of the COL4A3, COL4A4, and COL4A5 genes is the alpha345 collagen IV network, the major component of the mature glomerular basement membrane (GBM) as well as critical basement membranes in the cochlea and eye [14]. Pathogenic variants in these genes impair the formation and/or function of this network, with deleterious effects on glomerular, cochlear and ocular structures and physiology. Many of the downstream phenotypic effects of these molecular abnormalities take years to develop, such that affected individuals frequently present with oligo-symptomatic disease, especially in childhood and adolescence. Molecular diagnosis by next-generation sequencing or whole-exome sequencing is becoming the method of choice for establishing the diagnosis of Alport syndrome, gradually replacing diagnosis by clinical and histopathological evaluation.
Ultrastructural and immunofluorescence analysis of anterior lens capsules in autosomal recessive Alport syndrome
Published in Ophthalmic Genetics, 2021
Jiayue Zhou, Jing Wu, Qichuan Yin, Xiaoning Yu, Yilei Cui, Hao Yang, Xingchao Shentu
The patient was a 29-year-old man. He had a history of hematuria and proteinuria since he was 4 years old, and it gradually developed to stage 5 chronic kidney disease. Hearing loss and vision decrease also occurred as he aged. Eight years ago, he was diagnosed with autosomal recessive Alport syndrome (ARAS). He had a gene test in 2017, and mutation analysis of the COL4A4 gene revealed a c.4599 T > G mutation, which is a truncated mutation. His parents had a consanguineous marriage, and both carried the same mutation (Figure 1). However, none of his family members has the similar symptoms, including his parents and an elder sister.