Proxy Molecular Diagnosis from Whole-Exome Sequencing Reveals Papillon-Lefevre Syndrome Caused by a Missense Mutation in CTSC

Erzurumluoglu, A. Mesut; Alsaadi, Muslim M.; Rodríguez, Santiago; Alotaibi, Tahani S.; Guthrie, Philip A. I.; Lewis, Siân; Ginwalla, Aasiya; Gaunt, Tom R.; Alharbi, Khalid Khalaf; Alsaif, Fahad; Alsaadi, Basma M.; Day, Ian N.M.

doi:10.1371/journal.pone.0121351

Cited by 6 publications

(4 citation statements)

References 24 publications

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“…The patient was a 4‐year‐old girl without any obvious systemic diseases. According to the medical history provided by the patient's mother, skin abnormalities occurred 1 wk after the patient was born, earlier than that reported in most literature . The patient's teeth became loose when she was 2.5 years old.…”

Section: Resultsmentioning

confidence: 91%

A novel large deletion combined with a nonsense mutation in a Chinese child with Papillon–Lefèvre syndrome

Chen

et al. 2015

J of Periodontal Research

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Section: Resultsmentioning

confidence: 91%

A novel large deletion combined with a nonsense mutation in a Chinese child with Papillon–Lefèvre syndrome

Chen

et al. 2015

J of Periodontal Research

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“…Bacterial skin infections such as abscesses may also occur . The genetic etiology of PLS has been clearly established by sequencing of CTSC and whole exome sequencing . However, it still remains unclear why a lack of CatC activity leads to specific dermatological lesions and severe destructive periodontitis.…”

Section: Discussionmentioning

confidence: 99%

Analysis of urinary cathepsin C for diagnosing Papillon–Lefèvre syndrome

et al. 2016

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Papillon–Lefèvre syndrome (PLS) (OMIM: 245000) is a rare disease characterized by severe periodontitis and palmoplantar keratoderma. It is caused by mutations in both alleles of the cathepsin C (CatC) gene CTSC that completely abrogate the proteolytic activity of this cysteine proteinase. Most often, a genetic analysis to enable early and rapid diagnosis of PLS is unaffordable or unavailable. In this study, we tested the hypothesis that active CatC is constitutively excreted and can be easily traced in the urine of normal subjects. If this is true, determining its absence in the urine of patients would be an early, simple, reliable, low‐cost and easy diagnostic technique. All 75 urine samples from healthy control subjects (aged 3 months to 80 years) contained proteolytically active CatC and its proform, as revealed by kinetic analysis and immunochemical detection. Of the urine samples of 31 patients with a PLS phenotype, 29 contained neither proteolytically active CatC nor the CatC antigen, so that the PLS diagnosis was confirmed. CatC was detected in the urine of the other two patients, and genetic analysis revealed no loss‐of‐function mutation in CTSC, indicating that they suffer from a PLS‐like condition but not from PLS. Screening for the absence of urinary CatC activity soon after birth and early treatment before the onset of PLS manifestations will help to prevent aggressive periodontitis and loss of many teeth, and should considerably improve the quality of life of PLS patients.

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“…When the patients were referred to this clinic lab, informed consent was obtained from all of them. For minors, written parental consent was obtained, with the recognition that positive findings would be diagnostically reconfirmed in conjunction with clinical symptoms and other confirmatory tests [9]. …”

Section: Methodsmentioning

confidence: 99%

Frequency of Inborn Errors of Metabolism in a Northeastern Iranian Sample with High Consanguinity Rates

Keyfi¹,

Nasseri²,

Nayerabadi³

et al. 2018

Hum Hered

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Objective: Inborn errors of metabolism (IEMs) are disorders with various manifestations that occur mainly in the pediatric population. In countries where consanguineous marriage is common, the association between consanguinity and IEMs is highly important. No studies have been conducted in Iran examining the impact of consanguinity on IEMs. Methods: In this retrospective study, the incidences of metabolic disorders were evaluated for the years 2006 through 2016 in the North East Iran Regional Diagnostic Laboratory (Pardis Clinical and Genetic Laboratory). A total of 13,327 infants with clinical symptoms were referred and investigated for IEMs. Newborn screening was performed on samples from all patients suspected of having IEMs. Results: Of 13,327 infants examined, 60 different IEMs were diagnosed in 1,118. The most frequent disorders among our patients were glucose-6-phosphate dehydrogenase deficiency (G6PDD) (14.04%), methylmalonic and propionic acidurias (MMA/PA) (9.12%), phenylketonuria (PKU) (8%), and isovaleric acidemia (IVA) (6.98%). A significant difference was found in the prevalence of amino acid disorders between the offspring of consanguineous and those of non-consanguineous parents. No statistically significant differences were found between the 2 groups for organic or fatty acids, carnitine or urine cycles, or lysosomal storage disorders. A total of 707 of the 1,118 infants with metabolic diseases (63.24%) were children of consanguineous parents. These findings show that consanguinity can be an important factor in the inheritance of recessive mutations in a homozygous state. Conclusion: This study found a greater frequency of metabolic diseases in offspring of consanguineous parents than in those of non-consanguineous parents in a population with a high rate of consanguinity.

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Proxy Molecular Diagnosis from Whole-Exome Sequencing Reveals Papillon-Lefevre Syndrome Caused by a Missense Mutation in CTSC

Cited by 6 publications

References 24 publications

A novel large deletion combined with a nonsense mutation in a Chinese child with Papillon–Lefèvre syndrome

A novel large deletion combined with a nonsense mutation in a Chinese child with Papillon–Lefèvre syndrome

Analysis of urinary cathepsin C for diagnosing Papillon–Lefèvre syndrome

Frequency of Inborn Errors of Metabolism in a Northeastern Iranian Sample with High Consanguinity Rates

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