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Case Report: Japanese Siblings of Cystic Fibrosis With a Novel Large Heterozygous Deletion in the CFTR Gene

Cystic fibrosis (CF) is a rare disease in the Japanese. The most common CFTR variant in Japanese CF patients is a large heterozygous deletion that can easily avoid detection by standard gene sequencing methods. We herein report a novel large heterozygous deletion in the CFTR gene in Japanese sibling...

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Autores principales: Kawase, Mayumi, Ogawa, Masato, Hoshina, Takayuki, Kojiro, Masumi, Nakakuki, Miyuki, Naruse, Satoru, Ishiguro, Hiroshi, Kusuhara, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762059/
https://www.ncbi.nlm.nih.gov/pubmed/35047466
http://dx.doi.org/10.3389/fped.2021.800095
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author Kawase, Mayumi
Ogawa, Masato
Hoshina, Takayuki
Kojiro, Masumi
Nakakuki, Miyuki
Naruse, Satoru
Ishiguro, Hiroshi
Kusuhara, Koichi
author_facet Kawase, Mayumi
Ogawa, Masato
Hoshina, Takayuki
Kojiro, Masumi
Nakakuki, Miyuki
Naruse, Satoru
Ishiguro, Hiroshi
Kusuhara, Koichi
author_sort Kawase, Mayumi
collection PubMed
description Cystic fibrosis (CF) is a rare disease in the Japanese. The most common CFTR variant in Japanese CF patients is a large heterozygous deletion that can easily avoid detection by standard gene sequencing methods. We herein report a novel large heterozygous deletion in the CFTR gene in Japanese siblings with CF. A genetic analysis was performed in two patients (9-year-old boy and 5-month-old girl) who were clinically diagnosed with CF because of the positive result for the rapid fecal pancreatic elastase antigen test and the elevation of the sweat chloride concentration. In addition to conventional polymerase chain reaction (PCR) and direct sequencing, multiplex ligation-dependent probe amplification (MLPA) was performed to check for a large deletion and duplication of the CFTR gene. Based on MLPA findings, the breakpoint of heterozygous deletion was identified by real-time quantitative PCR followed by the sequence of the amplified junction fragment. In MLPA, the numbers of the fragments corresponding to exons 1, 16, 17a, and 17b and 234 nt and 747 nt upstream from the translation initiation codon of exon 1 in the CFTR gene and exon 3 in the ASZ1 gene were reduced by almost half. The c.2908+1085_3367+260del7201 variant (exon 16-17b deletion) was identified in one allele. The other allele had a large 137,567-bp deletion from g.117,361,112 (ASZ1 3′ flanking region) to g.117,498,678 (CFTR intron 1) on chromosome 7. Since the deletion variant lacked the entire promoter region of CFTR, CFTR mRNA would not be transcribed from the allele, indicating it to be a novel pathogenic variant causing CF. As large mutations are frequently detected in Japanese CF patients, MPLA can be useful when searching for variants.
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spelling pubmed-87620592022-01-18 Case Report: Japanese Siblings of Cystic Fibrosis With a Novel Large Heterozygous Deletion in the CFTR Gene Kawase, Mayumi Ogawa, Masato Hoshina, Takayuki Kojiro, Masumi Nakakuki, Miyuki Naruse, Satoru Ishiguro, Hiroshi Kusuhara, Koichi Front Pediatr Pediatrics Cystic fibrosis (CF) is a rare disease in the Japanese. The most common CFTR variant in Japanese CF patients is a large heterozygous deletion that can easily avoid detection by standard gene sequencing methods. We herein report a novel large heterozygous deletion in the CFTR gene in Japanese siblings with CF. A genetic analysis was performed in two patients (9-year-old boy and 5-month-old girl) who were clinically diagnosed with CF because of the positive result for the rapid fecal pancreatic elastase antigen test and the elevation of the sweat chloride concentration. In addition to conventional polymerase chain reaction (PCR) and direct sequencing, multiplex ligation-dependent probe amplification (MLPA) was performed to check for a large deletion and duplication of the CFTR gene. Based on MLPA findings, the breakpoint of heterozygous deletion was identified by real-time quantitative PCR followed by the sequence of the amplified junction fragment. In MLPA, the numbers of the fragments corresponding to exons 1, 16, 17a, and 17b and 234 nt and 747 nt upstream from the translation initiation codon of exon 1 in the CFTR gene and exon 3 in the ASZ1 gene were reduced by almost half. The c.2908+1085_3367+260del7201 variant (exon 16-17b deletion) was identified in one allele. The other allele had a large 137,567-bp deletion from g.117,361,112 (ASZ1 3′ flanking region) to g.117,498,678 (CFTR intron 1) on chromosome 7. Since the deletion variant lacked the entire promoter region of CFTR, CFTR mRNA would not be transcribed from the allele, indicating it to be a novel pathogenic variant causing CF. As large mutations are frequently detected in Japanese CF patients, MPLA can be useful when searching for variants. Frontiers Media S.A. 2022-01-03 /pmc/articles/PMC8762059/ /pubmed/35047466 http://dx.doi.org/10.3389/fped.2021.800095 Text en Copyright © 2022 Kawase, Ogawa, Hoshina, Kojiro, Nakakuki, Naruse, Ishiguro and Kusuhara. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Kawase, Mayumi
Ogawa, Masato
Hoshina, Takayuki
Kojiro, Masumi
Nakakuki, Miyuki
Naruse, Satoru
Ishiguro, Hiroshi
Kusuhara, Koichi
Case Report: Japanese Siblings of Cystic Fibrosis With a Novel Large Heterozygous Deletion in the CFTR Gene
title Case Report: Japanese Siblings of Cystic Fibrosis With a Novel Large Heterozygous Deletion in the CFTR Gene
title_full Case Report: Japanese Siblings of Cystic Fibrosis With a Novel Large Heterozygous Deletion in the CFTR Gene
title_fullStr Case Report: Japanese Siblings of Cystic Fibrosis With a Novel Large Heterozygous Deletion in the CFTR Gene
title_full_unstemmed Case Report: Japanese Siblings of Cystic Fibrosis With a Novel Large Heterozygous Deletion in the CFTR Gene
title_short Case Report: Japanese Siblings of Cystic Fibrosis With a Novel Large Heterozygous Deletion in the CFTR Gene
title_sort case report: japanese siblings of cystic fibrosis with a novel large heterozygous deletion in the cftr gene
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762059/
https://www.ncbi.nlm.nih.gov/pubmed/35047466
http://dx.doi.org/10.3389/fped.2021.800095
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