Differential impact of consanguineous marriages on autosomal recessive diseases in <scp>T</scp>unisia

Hsouna, Sana; Lasram, Khaled; Rejeb, Imen; Walha, Asma; Talmoudi, Faten; Messai, Habib; Brick, Ahlem Sabrine Ben; Ouragini, Houyem; Cherif, Wafa; Nagara, Majdi; Rhouma, Faten Ben; Chouchene, Ibtissem; Ouechtati, Farah; Bouyacoub, Yosra; Rekaya, Mariem Ben; Messaoud, Olfa; Ammar, Slim Ben; Matri, L. El; Tebib, Néji; Dridi, M. F. Ben; Mokni, M.; Amouri, Ahlem; Kéfi, Rym; Abdelhak, Sonia

doi:10.1002/ajhb.22764

Cited by 23 publications

(25 citation statements)

References 35 publications

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“…Among 19 Syrian GD patients, the consanguinity rate was 82%, which is very similar to our results [40], while among 425 Tunisian GD patients the consanguinity was (64.94%) [41].…”

Section: Discussionsupporting

confidence: 89%

Twenty- five years of biochemical diagnosis of Gaucher disease: the Egyptian experience

Fateen

Abdallah

2019

Heliyon

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BackgroundGaucher disease is a rare multi-systemic metabolic disorder resulting from the deficiency of acid β-glucosidase activity, with consequent accumulation of glucocerebroside. Less than 15% of mean normal acid β-glucosidase activity in leukocytes is the gold standard for the diagnosis of Gaucher disease, and is generally supplemented by a massive elevation in chitotriosidase activity. We report here our experience in the biochemical diagnosis of Gaucher disease by showing the heterogeneity of the activity of enzymes over 25 years from 1993-2017, through the analysis of 5128 clinically suspected Gaucher disease cases referred to the Biochemical Genetics Department, National Research Centre, as the main reference lab in Egypt for the diagnosis of Inherited Metabolic Disorders.MethodsAcid β-glucosidase and chitotriosidase activities were measured in all referred cases. Sphinogmylinase activity was estimated for all cases with normal β-glucosidase activity and moderate elevation of chitotriosidase.ResultsOut of the 5128 suspected cases, 882 (17%) showed a deficiency in acid β-glucosidase activity, accompanied by a raised chitotriosidase activity, ranges (213-66700 umol/l/h) and mean (7255 umol/l/h). Deficient chitotriosidase activity was found in 9 patients (1%) with low β-glucosidase. 451 cases were diagnosed with acid sphingomyelinase deficiency patients (8.8%).ConclusionOther biochemical markers are needed in addition to chitotriosidase for the diagnosis and follow up. Molecular testing was done to a relatively small number but needs to be done to all diagnosed patients as many mutations are known to predict the course of the disease.

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“…Among 19 Syrian GD patients, the consanguinity rate was 82%, which is very similar to our results [40], while among 425 Tunisian GD patients the consanguinity was (64.94%) [41].…”

Section: Discussionsupporting

confidence: 89%

Twenty- five years of biochemical diagnosis of Gaucher disease: the Egyptian experience

Fateen

Abdallah

2019

Heliyon

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“…The emergence of an XP-G form that we identified here is also likely due to the high rate of consanguinity. Indeed, we have shown that consanguineous unions increase the risk of autosomal recessive diseases occurrence more than sixfold in the Tunisian population (Ben Halim et al, 2016).…”

Section: Discussionmentioning

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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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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“…2,4 In Tunisia, consanguinity is common. 5 However, little information exists on its impact on recessive disorders such as ARO. To our knowledge, only two Tunisian cases have been reported.…”

Section: Discussionmentioning

confidence: 99%

Clinical and imaging features of malignant infantile osteopetrosis

Tfifha¹,

Gaha²,

Gamaoun³

et al. 2017

Turk J Pediatr

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Tfifha M, Gaha M, Gamaoun W, Chemli J, Mabrouk S, Hassayoun S, Zouari N, Jemni H, Abroug S. Clinical and imaging features of malignant infantile osteopetrosis. Turk J Pediatr 2017; 59: 452-457. Human osteopetrosis is a rare genetic disorder caused by osteoclast failure. It encompasses a group of highly heterogeneous forms, ranged widely in severity. Patients with autosomal recessive osteopetrosis are the most severely affected osteopetrotic patients. Here we describe Tunisian children with severe phenotype. They are native from the same geographic region, born to consanguineous parents. Clinical features were cranio-facial dysmorphy, macrocephaly, hepatosplenomegaly, severe anemia and thrombocytopenia with precocious onset of neuronopathic complications, blindness and deafness. Retinal atrophy, reported in a minority of forms is highlighted. Skeletal radiographs revealed generalized increase in bone density and abnormal metaphyseal remodeling, and superimposed rickets resulting from the defect in osteoclasts to provide a normal Ca/P balance. We report an exceptional association with congenital hypothyroidism. Multi-organ failure due to sepsis is one the most severe complications observed. The issue was fatal without hematopoietic stem cell transplantation.

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Differential impact of consanguineous marriages on autosomal recessive diseases in Tunisia

Cited by 23 publications

References 35 publications

Twenty- five years of biochemical diagnosis of Gaucher disease: the Egyptian experience

Twenty- five years of biochemical diagnosis of Gaucher disease: the Egyptian experience

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

Clinical and imaging features of malignant infantile osteopetrosis

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