Whole Exome Sequencing allows the identification of two novel groups of Xeroderma pigmentosum in Tunisia, XP-D and XP-E: Impact on molecular diagnosis

Rekaya, Mariem Ben; Naouali, Chokri; Messaoud, Olfa; Jones, M.; Bouyacoub, Yosra; Nagara, Majdi; Pippucci, Tommaso; Jmel, Haifa; Chargui, Mariem; Jerbi, M.; Alibi, Mohamed; Dallali, Hamza; Bashamboo, Anu; McElreavey, Kenneth; Romeo, Giovanni; Barakat, Abdelhamid; Zghal, M.; Yacoub‐Youssef, Houda; Abdelhak, Sonia

doi:10.1016/j.jdermsci.2017.10.015

Cited by 16 publications

(14 citation statements)

References 43 publications

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“…Due to the high frequency of consanguineous unions, this region harbors many rare recessive genetic diseases (Romdhane et al, 2012). Regarding XP in this region, we observed a high frequency of XP-A patients carrying the p.R228 ∗ mutation presenting with a severe neurological phenotype, moreover a few families manifest mild forms of the disease like XP-D (Ben Rekaya et al, 2018). The emergence of an XP-G form that we identified here is also likely due to the high rate of consanguinity.…”

Section: Discussionmentioning

confidence: 89%

“…The mutations with founder effect responsible for the XP-C (Ben Rekaya et al, 2009) and XP-A phenotypes (Messaoud et al, 2010) have been also found in other North African countries (Soufir et al, 2010) such as Morocco (Senhaji et al, 2013; Kindil et al, 2017), Egypt (Amr et al, 2014), Algeria (Bensenouci et al, 2016), and Libya (unpublished data). The XP-D and XP-E forms have been recently identified thanks to whole exome sequencing (WES) technology (Ben Rekaya et al, 2018). Patients belonging to these last two groups had mild dermatological manifestations, absence of neurological anomalies, and late onset of skin tumors.…”

Section: Introductionmentioning

confidence: 99%

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Identification of a ERCC5 c.2333T>C (L778P) Variant in Two Tunisian Siblings With Mild Xeroderma Pigmentosum Phenotype

et al. 2019

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Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder due to a defect in the nucleotide excision repair (NER) DNA repair pathway, characterized by severe sunburn development of freckles, premature skin aging, and susceptibility to develop cancers at an average age of eight. XP is an example of accelerated photo-aging. It is a genetically and clinically heterogeneous disease. Eight complementation groups have been described worldwide. In Tunisia, five groups have been already identified. In this work, we investigated the genetic etiology in a family with an atypically mild XP phenotype. Two Tunisian siblings born from first-degree consanguineous parents underwent clinical examination in the dermatology department of the Charles Nicolle Hospital on the basis of acute sunburn reaction and mild neurological disorders. Blood samples were collected from two affected siblings after written informed consent. As all mutations reported in Tunisia have been excluded using Sanger sequencing, we carried out mutational analysis through a targeted panel of gene sequencing using the Agilent HaloPlex target enrichment system. Our clinical study shows, in both patients, the presence of achromic macula in sun exposed area with dermatological feature suggestive of Xeroderma pigmentosum disease. No developmental and neurological disorders were observed except mild intellectual disability. Genetic investigation shows that both patients were carriers of an homozygous T to C transition at the nucleotide position c.2333, causing the leucine to proline amino acid change at the position 778 (p.Leu778Pro) of the ERCC5 gene, and resulting in an XP-G phenotype. The same variation was previously reported at the heterozygous state in a patient cell line in Europe, for which no clinical data were available and was suggested to confer an XP/CS phenotype based on functional tests. This study contributes to further characterization of the mutation spectrum of XP in consanguineous Tunisian families and is potentially helpful for early diagnosis. It also indicates that the genotype-phenotype correlation is not always coherent for patients with mild clinical features. These data therefore suggest that targeted NGS is a highly informative diagnostic strategy, which can be used for XP molecular etiology determination.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Identification of a ERCC5 c.2333T>C (L778P) Variant in Two Tunisian Siblings With Mild Xeroderma Pigmentosum Phenotype

et al. 2019

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“…To the best of our knowledge, only 17 XP-E patients have been reported until now [12][13][14]. The mutations of DDB2 identified in all XPE patients are summarized in Table 1.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel DDB2 mutation in a Chinese Han family with Xeroderma pigmentosum group E:a case report and literature review

et al. 2020

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Background: Xeroderma pigmentosum (XP) is a rare autosomal recessive genodermatosis. There are eight complementation groups of XP (XP-A to G and a variant form). XP-E is one of the least common forms, and XP-E patients are generally not diagnosed until they are adults due to a later onset of skin alterations. Case presentation: We report a case of a 28-year-old Chinese woman with freckle-like hyperpigmented macules in a sun-exposed area who is prone to develop basal cell carcinomas. A genetic study revealed a novel homozygous c.111_112del deletion in exon 1 of the DDB2 gene. Western blotting analysis revealed that the patient lacked the expression of the wild-type mature DDB2 protein. The proband was first diagnosed with XPE on the basis of clinical findings and genetic testing. Sun protection was recommended, and the patient did not develop any skin cancers during the one-year follow-up. Conclusions: We identified a novel homozygous deletion in DDB2 gene in Chinese XP-E patients having unique clinical features.

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“…This study identified the fisrt cases of complementation groups XP‐D and XP‐E in Tunisia and in North Africa. Pathogenic variants within the ERCC2 and DDB2 genes segregated in all affected family members (Ben Rekaya et al., ).…”

Section: Xeroderma Pigmentosum and Other Skin Disordersmentioning

confidence: 99%

Genetics and genomic medicine in Tunisia

Elloumi-Zghal¹,

Bouhamed

2018

Molec Gen & Gen Med

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Whole Exome Sequencing allows the identification of two novel groups of Xeroderma pigmentosum in Tunisia, XP-D and XP-E: Impact on molecular diagnosis

Abstract: To our knowledge, this is the first study that identifies XP-D and XP-E complementation groups in Tunisia. These two groups are very rare and under-diagnosed in the world and were not reported in North Africa.

Cited by 16 publications

References 43 publications

Identification of a ERCC5 c.2333T>C (L778P) Variant in Two Tunisian Siblings With Mild Xeroderma Pigmentosum Phenotype

Identification of a ERCC5 c.2333T>C (L778P) Variant in Two Tunisian Siblings With Mild Xeroderma Pigmentosum Phenotype

Identification of a novel DDB2 mutation in a Chinese Han family with Xeroderma pigmentosum group E:a case report and literature review

Genetics and genomic medicine in Tunisia

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