Mutation spectrum of glycogen storage disease type Ia in Tunisia: Implication for molecular diagnosis

Barkaoui, E.; Cherif, Wafa; Tebib, Néji; Charfeddine, Chérine; Rhouma, Faten Ben; Azzouz, Hatem; Chehida, Amel Ben; Monastiri, K.; Chemli, J.; Amri, Fethi; Turkia, Hadhami Ben; Abdelmoula, M.S.; Kaabachi, N.; Abdelhak, Sonia; Dridi, M. F. Ben

doi:10.1007/s10545-007-0737-1

Cited by 13 publications

(10 citation statements)

References 13 publications

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“…For XPA31TA/AL family, although parents are from two different north‐African countries (southern Tunisia and Algeria), the affected child shared a common haplotype at homozygous state as the other Tunisian families. This is not surprising as we have already shown for other genetic diseases, including genodermatosis, that a similar mutational spectrum is shared between Tunisian patients and others from different Mediterranean countries 15,16 . This recurrent mutation facilitates molecular investigation of XPA in this region particularly in countries where consanguinity is still culturally privileged.…”

Section: Commentsupporting

confidence: 67%

Genetic homogeneity of mutational spectrum of group‐A xeroderma pigmentosum in Tunisian patients

et al. 2010

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The XPA R228X mutation is common in Tunisian population. This mutation is associated with a relatively moderate phenotype of the XPA. As all explored patients presented the recurrent mutation XPA R228X, a potential founder effect was searched and confirmed by haplotype analysis. Taking into account similar genetic background, investigation of this mutation should allow a cost effective and rapid diagnosis of XPA in north-African populations.

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Section: Commentsupporting

confidence: 67%

Genetic homogeneity of mutational spectrum of group‐A xeroderma pigmentosum in Tunisian patients

et al. 2010

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“…This was the case for glycogenosis type Ia. Indeed, in the Tunisian population, two mutations in the G6PC gene, p.R38C and p.R170Q, account for more than 90% of mutations [96]. Therefore, developing direct DNA mutation analysis of the G6Pase gene allowed rapid carrier testing and avoided performing a liver biopsy for the biochemical confirmation [96].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, in the Tunisian population, two mutations in the G6PC gene, p.R38C and p.R170Q, account for more than 90% of mutations [96]. Therefore, developing direct DNA mutation analysis of the G6Pase gene allowed rapid carrier testing and avoided performing a liver biopsy for the biochemical confirmation [96]. For such disease and for some others, establishing the molecular basis allows a safer and less invasive diagnostic test therefore making it more acceptable and bearable to patients and their families.…”

Section: Discussionmentioning

confidence: 99%

Founder mutations in Tunisia: implications for diagnosis in North Africa and Middle East

Romdhane

Kéfi

Azaiez

et al. 2012

Orphanet J Rare Dis

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BackgroundTunisia is a North African country of 10 million inhabitants. The native background population is Berber. However, throughout its history, Tunisia has been the site of invasions and migratory waves of allogenic populations and ethnic groups such as Phoenicians, Romans, Vandals, Arabs, Ottomans and French. Like neighbouring and Middle Eastern countries, the Tunisian population shows a relatively high rate of consanguinity and endogamy that favor expression of recessive genetic disorders at relatively high rates. Many factors could contribute to the recurrence of monogenic morbid trait expression. Among them, founder mutations that arise in one ancestral individual and diffuse through generations in isolated communities.MethodWe report here on founder mutations in the Tunisian population by a systematic review of all available data from PubMed, other sources of the scientific literature as well as unpublished data from our research laboratory.ResultsWe identified two different classes of founder mutations. The first includes founder mutations so far reported only among Tunisians that are responsible for 30 genetic diseases. The second group represents founder haplotypes described in 51 inherited conditions that occur among Tunisians and are also shared with other North African and Middle Eastern countries. Several heavily disabilitating diseases are caused by recessive founder mutations. They include, among others, neuromuscular diseases such as congenital muscular dystrophy and spastic paraglegia and also severe genodermatoses such as dystrophic epidermolysis bullosa and xeroderma pigmentosa.ConclusionThis report provides informations on founder mutations for 73 genetic diseases either specific to Tunisians or shared by other populations. Taking into account the relatively high number and frequency of genetic diseases in the region and the limited resources, screening for these founder mutations should provide a rapid and cost effective tool for molecular diagnosis. Indeed, our report should help designing appropriate measures for carrier screening, better evaluation of diseases burden and setting up of preventive measures at the regional level.

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“…- in Tunisian patients, p.R83C and p.R170Q accounts for 67% and 28% of the alleles respectively [76]. …”

Section: Etiologymentioning

confidence: 99%

Glucose-6-phosphatase deficiency

Froissart

Piraud

Boudjemline

et al. 2011

Orphanet J Rare Dis

189

159

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Glucose-6-phosphatase deficiency (G6P deficiency), or glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea). Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty), generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma) and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency). GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia) which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib). Mutations in the genes G6PC (17q21) and SLC37A4 (11q23) respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most commonly confirmed by G6PC (GSDIa) or SLC37A4 (GSDIb) gene analysis, and the indications of liver biopsy to measure G6P activity are getting rarer and rarer. Differential diagnoses include the other GSDs, in particular type III (see this term). However, in GSDIII, glycemia and lactacidemia are high after a meal and low after a fast period (often with a later occurrence than that of type I). Primary liver tumors and Pepper syndrome (hepatic metastases of neuroblastoma) may be evoked but are easily ruled out through clinical and ultrasound data. Antenatal diagnosis is possible through molecular analysis of amniocytes or chorionic villous cells. Pre-implantatory genetic diagnosis may also be discussed. Genetic counseling should be offered to patients and their families. The dietary treatment aims at avoiding hypoglycemia (frequent meals, nocturnal enteral feeding through a nasogastric tube, and later oral addition of uncooked starch) and acidosis (restricted fructose and galactose intake). Liver transplantation, performed on the basis of poor metabolic control and/or hepatoc...

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Mutation spectrum of glycogen storage disease type Ia in Tunisia: Implication for molecular diagnosis

Cited by 13 publications

References 13 publications

Genetic homogeneity of mutational spectrum of group‐A xeroderma pigmentosum in Tunisian patients

Genetic homogeneity of mutational spectrum of group‐A xeroderma pigmentosum in Tunisian patients

Founder mutations in Tunisia: implications for diagnosis in North Africa and Middle East

Glucose-6-phosphatase deficiency

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