Identification of a novel protein truncating mutation p.Asp98* in <i>XPC</i> associated with xeroderma pigmentosum in a consanguineous Pakistani family

Ali, Muhammad; Blatterer, Jasmin; Khan, Muzammil Ahmad; Schaflinger, Erich; Petek, Erwin; Ahmad, Safeer; Khan, Ejazullah; Windpassinger, Christian

doi:10.1002/mgg3.1060

Cited by 5 publications

(4 citation statements)

References 28 publications

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“…Present study is the third report of XPC mutational analysis from Pakistani population. Previously, Ali et al 1 and Ijaz et al 6 have reported only three mutations (IVS12–1 G>C; p.Gln467*; p.Asp98*) in the XPC gene in families of Pakistani origin.…”

Section: Discussionmentioning

confidence: 95%

Loss of Function Variants in the XPC Causes Severe Xeroderma Pigmentosum in Three Large Consanguineous Families

Nawal

Ullah

et al. 2021

Klin Padiatr

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Background Xeroderma pigmentosum (XP) is a rare recessively inherited disorder that presents clinical and genetic heterogeneity. Mutations in eight genes, of which seven are involved in nucleotide excision repair (NER) pathway have been reported to cause the XP. Methods and Results Three large consanguineous families of Pakistani origin displaying typical clinical hallmarks of XP were evaluated at clinical and molecular level. Homozygosity mapping using microsatellite markers established linkage of the families to XPC gene on chromosome 3p25.1. Sanger sequencing of the XPC gene identified a novel homozygous single bp deletion [NM_004628.5; c.1934del; p.(Pro645Leufs*5)] and two previously reported mutations that included a nonsense [c.1243 C>T; p.(Arg415*)] and a splice acceptor site (c.2251–1 G>C), all segregating with the disease phenotypes in the families. Conclusion This report has extended the spectrum of mutations in the XPC gene and will also facilitate in diagnosis of XP and counselling of families inheriting it, which is the only inevitable tool for preventing the disease occurrence in future generations.

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Section: Discussionmentioning

confidence: 95%

Loss of Function Variants in the XPC Causes Severe Xeroderma Pigmentosum in Three Large Consanguineous Families

Nawal

Ullah

et al. 2021

Klin Padiatr

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“…According to the Leiden Open Variation Database, over 280 different unique mutations throughout the coding region of FLCN have been identi ed to date. [15] The deletion or insertion of cytosine residues in exon 11 is a recognized mutation hotspot, with nearly half of patients carrying either c.1285delC or c.1285dupC mutations, which are consistent in both European and Asian populations. [2] Other patients have been found to have intragenic deletions or duplications and pathogenic missense mutations.…”

Section: Discussionmentioning

confidence: 98%

A novel mutation in the FLCN gene in a chinese family with Birt-Hogg-Dubé(BHD) syndrome

Miao,

Zhou,

et al. 2024

Preprint

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Background Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited syndrome caused by folliculin (FLCN) mutation, and FLCN is identified as a tumor suppressor gene. The main objective of this study was to identify disease-causing mutations in a Chinese family affected with BHDS. Methods A chinese proband was diagnosed with BHDS for renal tumors, a novel variant in the FLCN gene was identified by next-generation sequencing (NGS). Sanger sequencing was conducted on blood samples from family members to validate the presence of this mutation. Results A novel germline frameshift variant (NM_144997.5:c.977dup) was detected in affected family members. Additionally, a somatic frameshift mutation (NM_144997.5:c.1252del) was also detected in the renal tumors of the proband. No mutation was detected in unaffected family members. The mutation seems to be more likely to develop BHDS-associated renal tumors. Conclusions A novel mutation was detected in the FLCN gene. It expands the spectrum of FLCN mutations, provides insights into genotype-phenotype correlations of BHDS and a basis for the diagnosis value of testing for FLCN mutations in patients with suspected BHDS.

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“…In this study, we presented a novel frameshift variant (c.912delT/p.E305KfsX18) in exon 9 of the FLCN gene, which has not been previously reported in individuals with BHDS. Frameshift mutation may lead to an early termination of protein synthesis or to nonsense-mediated mRNA decay in which the defective mRNA is prematurely degraded ( Ali et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Pathogenic Folliculin Variant in a Chinese Family With Birt–Hogg–Dubé Syndrome (Hornstein-Knickenberg Syndrome)

Zong

Liu

et al. 2020

Front. Genet.

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Birt-Hogg-Dubé syndrome (BHDS), which is also called Hornstein-Knickenberg syndrome (HKS), is a hereditary autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN, NM_144997). More pulmonary manifestations (pulmonary cysts and recurrent pneumothoraxes) but fewer skin fibrofolliculomas and renal malignancy are found in Asian BHDS patients compared with other BHDS patients. The atypical manifestation can easily lead to a missed or delayed diagnosis. Here, we report a Chinese family with BHDS that presented with primary spontaneous pneumothorax (PSP) and extensive pulmonary cysts in the absence of skin lesions or renal neoplasms. Next-generation sequencing (NGS) was used to sequence the FLCN gene, and Sanger sequencing was carried out on the samples to confirm the presence of these variants. Among the 13 family members, a novel frameshift variant of FLCN (c.912delT/p.E305KfsX18) was identified in seven individuals. This variant has not been reported before. Bioinformatics analysis showed that the novel variant might lead to a premature stop codon after 18 amino acid residues in exon 9, and this may affect the expression level of FLCN. The identification of this novel frameshift variant of FLCN not only further confirms the familial inheritance of BHDS in the proband but also expands the mutational spectrum of the FLCN gene in patients with BHDS.

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Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family

Cited by 5 publications

References 28 publications

Loss of Function Variants in the XPC Causes Severe Xeroderma Pigmentosum in Three Large Consanguineous Families

Loss of Function Variants in the XPC Causes Severe Xeroderma Pigmentosum in Three Large Consanguineous Families

A novel mutation in the FLCN gene in a chinese family with Birt-Hogg-Dubé(BHD) syndrome

Identification of a Novel Pathogenic Folliculin Variant in a Chinese Family With Birt–Hogg–Dubé Syndrome (Hornstein-Knickenberg Syndrome)

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