Next-generation sequencing for identifying a novel/de novo pathogenic variant in a Mexican patient with cystic fibrosis: a case report

Martínez‐Hernández, Angélica; Larrosa, J; Barajas‐Olmos, Francisco; Garcia‐Ortíz, Humberto; Mendoza-Caamal, Elvia; Contreras-Cubas, Cecilia; Mirzaeicheshmeh, Elaheh; Lezana, José Luis; Orozco, Lorena

doi:10.1186/s12920-019-0528-1

Cited by 3 publications

(5 citation statements)

References 30 publications

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“…Variants occurring de novo in the CFTR gene are extremely rare, with approximately 10 cases of de novo CFTR variants published to date. 58 There was an interesting finding that two de novo variants (c.960dupA[p.Ser321IlefsX43] and c.2491-2A>G) were identified among Chinese, which were confirmed after paternity test as well as CFTR gene screening for the biological parents. Furthermore, both de novo variants were found in Beijing Children’s Hospital.…”

Section: Discussionmentioning

confidence: 99%

Genetic spectrum of Chinese children with cystic fibrosis: comprehensive data analysis from the main referral centre in China

et al. 2022

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Background and objectivesCystic fibrosis (CF) is a heterogeneous disease with a diverse genetic spectrum among populations. Few patients with CF of Chinese origin have been reported worldwide. The objective of this study is to characterise the genotypic features of CF in Chinese children.MethodsWe recruited and characterised the genetic manifestations of 103 Chinese children with CF in Beijing Children’s Hospital from 2010 to 2022. Whole-exome sequencing were performed to define the genotypes. Meanwhile, other 99 genetically confirmed patients with Chinese origin described in 45 references were also summarised.Results158 different variants including 23 novel observations were identified after sequencing. The majority of CFTR variants (82.3%) in Chinese have been observed only once or twice. 43.7% of the variants were only identified in patients of Chinese origin. The c.2909G>A(p.Gly970Asp), c.1766+5G>T and c.1657C>T(p.Arg553X) were the most frequent variants among Chinese patients, with allele frequency of 12.1%, 5.4% and 3.6%, respectively. The first two variants both showed significant Chinese ethnic tendency, while the latter one most likely came from Europeans for historical reasons. They also demonstrated significant differences in geographical distribution. c.1521_1523delCTT(p.F508del) was rarely observed in patients of pure Chinese origin, with an allele frequency of 1.8%. Two de novo variants (c.960dupA[p.Ser321IlefsX43] and c.2491-2A>G) and two deep-intronic variants (c.3718–2477C>T and c.3874-4522A>G) were identified, which were also quite rare among Chinese.ConclusionsThe genetic spectrum of CF in Chinese is unique and quite different from that observed in Caucasians. The geographical distributions of the most frequent variants were reported for the first time.

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Section: Discussionmentioning

confidence: 99%

Genetic spectrum of Chinese children with cystic fibrosis: comprehensive data analysis from the main referral centre in China

et al. 2022

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“…As the molecular diagnosis of the disease in Mexico is very complex, and because Mexico is a middle-income country, we applied a combination of methodologies. As a first step, we screened for the five most frequent mutations by PSM [ 10 , 12 ], a low-cost tool that allowed us to identify more than 40% of the alleles. This step was followed by PV screening using NGS and MLPA.…”

Section: Discussionmentioning

confidence: 99%

“…The molecular screening was performed in two steps. First, we screened the five most frequent PVs in the Mexican population [p.(Ile507del), p.(Phe508del), p.(Gly542*), p.(Ser549Asn), and p.(Asn1303Lys)] using PCR-mediated site-directed mutagenesis (PSM) as described previously [ 10 , 12 ]. Second, in those patients with at least one unidentified allele, CFTR sequencing was performed using next-generation sequencing (NGS).…”

Section: Methodsmentioning

confidence: 99%

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CFTR pathogenic variants spectrum in a cohort of Mexican patients with cystic fibrosis

Martínez-Hernández,

Mendoza-Caamal,

Mendiola-Vidal

et al. 2024

Heliyon

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“… 10 As a result, only a few reports of de novo mutations in the CFTR gene have been published, with only 10 identified so far. 11 – 17 …”

Section: Introductionmentioning

confidence: 99%

Identification and in silico structural analysis for the first de novo mutation in the cystic fibrosis transmembrane conductance regulator protein in Iran: case report and developmental insight using microsatellite markers

Hosseini Nami,

Kabiri,

Zafarghandi Motlagh

et al. 2024

Ther Adv Respir Dis

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Cystic fibrosis (CF) is an autosomal recessive disease caused by the inheritance of two mutant cystic fibrosis transmembrane conductance regulator (CFTR) alleles, one from each parent. Autosomal recessive disorders are rarely associated with germline mutations or mosaicism. Here, we propose a case of paternal germline mutation causing CF. The subject also had an identifiable maternal mutant allele. We identified the compound heterozygous variants in the proband through Sanger sequencing, and in silico studies predicted functional effects on the protein. Also, short tandem repeat markers revealed the de novo nature of the mutation. The maternal mutation in the CFTR gene was c.1000C > T. The de novo mutation was c.178G > A, p.Glu60Lys. This mutation is located in the lasso motif of the CFTR protein and, according to in silico structural analysis, disrupts the interaction of the lasso motif and R-domain, thus influencing protein function. This first reported case of de novo mutation in Asia has notable implications for molecular diagnostics, genetic counseling, and understanding the genetic etiology of recessive disorders in the Iranian population.

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Next-generation sequencing for identifying a novel/de novo pathogenic variant in a Mexican patient with cystic fibrosis: a case report

Cited by 3 publications

References 30 publications

Genetic spectrum of Chinese children with cystic fibrosis: comprehensive data analysis from the main referral centre in China

Genetic spectrum of Chinese children with cystic fibrosis: comprehensive data analysis from the main referral centre in China

CFTR pathogenic variants spectrum in a cohort of Mexican patients with cystic fibrosis

Identification and in silico structural analysis for the first de novo mutation in the cystic fibrosis transmembrane conductance regulator protein in Iran: case report and developmental insight using microsatellite markers

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