Clinical, genealogical and molecular investigation of the xeroderma pigmentosum type C complementation group in Tunisia

Jerbi, M.; Rekaya, Mariem Ben; Naouali, Chokri; Jones, M.; Messaoud, Olfa; Tounsi, H.; Nagara, Majdi; Chargui, Mariem; Kéfi, Rym; Boussen, Hamouda; Mokni, M.; Mrad, Ridha; Boubaker, Mohamed Samir; Abdelhak, Sonia; Khaled, A.; Zghal, M.; Yacoub‐Youssef, Houda

doi:10.1111/bjd.14046

Cited by 24 publications

(29 citation statements)

References 16 publications

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“…Combination of rare pathogen variants in DNA repair genes with high or low penetrant variants in BRCA genes among Tunisian breast cancer cases might explain the relatively young onset age and the aggressive tumor types observed in some cases described in local epidemiological reports. Our previous studies have shown a relatively high rate of consanguinity 74,75 that increases the frequency of monogenic diseases such autosomal recessive DNA repair disorders predisposing to cancer and raise the prevalence of healthy carriers 76,77 ; (Ben Rekaya unpublished data).…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

Rekaya

Hamdi

Benna

et al. 2020

Preprint

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Background: Genetic risk factors of breast cancer are very heterogeneous and complex. They vary according to the familial relative risk, the age of cancer diagnosis of the index case and the age of the affected relatives.Objectives: We aimed to investigate and identify simultaneously all rare pathogenic and common variants in unrelated BC cases with different relative risk ratios for breast cancer and evaluate the contribution of these variants in genetic susceptibility to breast cancer.Patients and Methods: All frequent mutations in BRCA genes previously identified in Tunisia have been excluded by Sanger sequencing in 42 women affected with high family risk having at least 3 cancer affected related individuals. Two unrelated cases having two different family histories (in terms of different numbers of affected first-degree relatives and young age onset) have been selected for whole exome sequencing. The first family is composed of three sisters F1.1, F1.2 and F1.3 affected at 46, 50, and 32 years old, respectively. The second has only two breast cancer cases, F2.2 and F2.4, affected at late age 61 and 70 years old, respectively, in addition to other 5 members affected by different kinds of cancer. Selected high risk variants were confirmed and segregation analysis was performed using Sanger sequencing. Results and discussion: For F1.1 case, we identified a pathogenic frame-shift loss of function variant in BRCA2 p.Val1283Lysfs. For F2.2 we identified a pathogenic rare variant in OGG1, p.Arg46Gln that co-segregates with a rare non sense variant in BRCA2 p.K3326X, only in the breast cancer affected cases. Moreover, F2.2 patient has 9 other common low penetrant variants in different loci known to represent independently minor, but cumulatively significant, increased risk for breast cancer.Conclusion: Family history and the young age at onset for patient F1.1 correlate with the presence of a rare high penetrant variant (p.Val1283Lysfs) in BRCA2 gene. However, the late age at onset and the less severe phenotype for patient F2.2 are probably the consequence of the presence of a pathogenic variant p.Arg46Gln in OGG1 gene that co-segregate with a low penetrant variant Lys3326X in BRCA2 only in breast cancer cases.

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Section: Discussionmentioning

confidence: 99%

Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

Rekaya

Hamdi

Benna

et al. 2020

Preprint

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“…There is a Blood Commentary on this article in this issue. ERCC6L2 defines a novel entity within inherited acute myeloid leukemia Suvi P. M. Douglas, 1,2 Pihla Siipola, 1,2 Panu E. Kovanen, 3 Marja Pyörälä, 4 Sakari Kakko, 5 Eeva-Riitta Savolainen, 6 Urpu Salmenniemi, 7,8 Katri Orte, 9,10 Soili Kytölä, 11 Esa Pitkänen, 12 Kimmo Porkka, 13,14 Outi Kilpivaara, 1,2, * and Ulla Wartiovaara-Kautto Lack of ERCC6L2 results in defects in the transcription-coupled nucleotide excision repair pathway, leading to genome instability. 1 It also affects mitochondrial function, increasing reactive oxygen species levels and altering cellular homeostasis.…”

Section: Footnotesmentioning

confidence: 99%

“…4 XP frequency in Tunisia and carrier frequency in Morocco were estimated to be 1/10 000 and 1/250, respectively. 7,8 Whole-exome sequencing (WES) of germinal DNA was performed in 6 patients from distinct families, and in both parents in 3 patients. We detected, as expected, a high level of inbreeding (supplemental Table 2) and a Middle East population distribution of variants, except in patient #6, in whom variant distribution was at the boundary between Middle East and European populations (supplemental Figure 2).…”

mentioning

confidence: 99%

Familial predisposition to TP53/complex karyotype MDS and leukemia in DNA repair-deficient xeroderma pigmentosum

Sarasin

Quentin

Droin

et al. 2019

Blood

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“…Moreover, molecular investigation of 64 XP‐C patients belonging to 44 families revealed the presence of the c.1643_1644delTG mutation in 60 patients (94%) (Jerbi et al., ). A map of the distribution of XP‐C in Tunisia is available; please refer to Jerbi et al., ;. Some clusters of heterogeneity of the disease were recently reported, with the presence of a second founder mutation within exon 7 restricted to the south of the country (Ben Rekaya et al., ).…”

Section: Xeroderma Pigmentosum and Other Skin Disordersmentioning

confidence: 99%

“…One single mutation c.1643_1644delTG was identified, and haplotype analysis suggested a founder effect (Ben Rekaya et al, 2009). Moreover, molecular investigation of 64 XP-C patients belonging to 44 families revealed the presence of the c.1643_1644delTG mutation in 60 patients (94%) (Jerbi et al, 2016). A map of the distribution of XP-C in Tunisia is available; please refer to Jerbi et al, 2016;.…”

Section: And Other Skin Disordersmentioning

confidence: 99%

Genetics and genomic medicine in Tunisia

Elloumi-Zghal¹,

Bouhamed

2018

Molec Gen & Gen Med

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Clinical, genealogical and molecular investigation of the xeroderma pigmentosum type C complementation group in Tunisia

Cited by 24 publications

References 16 publications

Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

Whole exome sequencing reveals a combination of rare high and low penetrance variants that correlates with familial breast cancer relative risk

Familial predisposition to TP53/complex karyotype MDS and leukemia in DNA repair-deficient xeroderma pigmentosum

Genetics and genomic medicine in Tunisia

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