Background: The defect in chloride and sodium transport in cystic fibrosis (CF) patients is a consequence of CF transmembrane conductance
regulator (CFTR) loss of function and an abnormal interaction ...between CFTR and the epithelial sodium channel (ENaC). A few
patients were described with CF-like symptoms, a single CFTR mutation, and an ENaC mutation.
Methods: To study African patients with CF-like symptoms and to relate the disease to gene mutations of both CFTR and ENaC genes,
we collected clinical data and DNA samples from 60 African patients with a CF phenotype. The CFTR gene was first analyzed
in all patients by denaturing high-performance liquid chromatography followed by direct sequencing; whereas, the sodium channel
non-voltage-gated 1 α (SCNN1A), sodium channel non-voltage-gated 1 β (SCNN1B), and sodium channel non-voltage-gated 1 γ (SCNN1G)
subunits of the ENaC gene were analyzed by sequencing in the five patients who carried only one CF mutation. The frequency
of all identified ENaC variants was established in a control group of 200 healthy individuals and in the 55 CF-like patients
without any CFTR mutation.
Results: Three CFTR mutants, including one previously undescribed missense mutation (p.A204T), and a 5T/7T variant were identified
in five patients. ENaC gene sequencing in these five patients detected the following eight ENaC variants: c.72T>C and p.V573I
in SCNN1A; p.V348M, p.G442V, c.1473 + 28C>T, and p.T577T in SCNN1B; and p.S212S and c.1176 + 30G>C in SCNN1G. In the 55 CF-like
patients without any CFTR mutation, we identified five of these eight ENaC variants, including the frequent p.G442V polymorphism,
but we did not detect the presence of the p.V348M, p.T577T, and c.1176 + 30G>C ENaC variants. Moreover, these last three ENaC
variants, p.V348M, p.T577T, and c.1176 + 30G>C, were not found in the control group.
Conclusion: Our data suggest that CF-like syndrome in Africa could be associated with CFTR and ENaC mutations.
The defect in chloride and sodium transport in cystic fibrosis (CF) patients is a consequence of CF transmembrane conductance regulator (CFTR) loss of function and an abnormal interaction between ...CFTR and the epithelial sodium channel (ENaC). A few patients were described with CF-like symptoms, a single CFTR mutation, and an ENaC mutation.
To study African patients with CF-like symptoms and to relate the disease to gene mutations of both CFTR and ENaC genes, we collected clinical data and DNA samples from 60 African patients with a CF phenotype. The CFTR gene was first analyzed in all patients by denaturing high-performance liquid chromatography followed by direct sequencing; whereas, the sodium channel non-voltage-gated 1 alpha (SCNN1A), sodium channel non-voltage-gated 1 beta (SCNN1B), and sodium channel non-voltage-gated 1 gamma (SCNN1G) subunits of the ENaC gene were analyzed by sequencing in the five patients who carried only one CF mutation. The frequency of all identified ENaC variants was established in a control group of 200 healthy individuals and in the 55 CF-like patients without any CFTR mutation.
Three CFTR mutants, including one previously undescribed missense mutation (p.A204T), and a 5T/7T variant were identified in five patients. ENaC gene sequencing in these five patients detected the following eight ENaC variants: c.72T>C and p.V573I in SCNN1A; p.V348M, p.G442V, c.1473 + 28C>T, and p.T577T in SCNN1B; and p.S212S and c.1176 + 30G>C in SCNN1G. In the 55 CF-like patients without any CFTR mutation, we identified five of these eight ENaC variants, including the frequent p.G442V polymorphism, but we did not detect the presence of the p.V348M, p.T577T, and c.1176 + 30G>C ENaC variants. Moreover, these last three ENaC variants, p.V348M, p.T577T, and c.1176 + 30G>C, were not found in the control group.
Our data suggest that CF-like syndrome in Africa could be associated with CFTR and ENaC mutations.
We report on a child who died in the neonatal period. Major external anomalies included foetal overgrowth, macroglossia, and ambiguous genitalia (micropenis and perineoscrotal hypospadias with ...cryptorchidism). Necropsy showed a large right diaphragmatic hernia, visceromegaly, multicystic kidney dysplasia, Langerhans islet hyperplasia, nephroblastomatosis, multiple adrenal adenomas, and dysplastic testicles. The child illustrates the difficulties of the differential diagnosis of overgrowth syndromes in the neonatal period, and the phenotypic overlap of Beckwith-Wiedemann, Denys-Drash, Simpson-Golabi-Behmel, Perlman and possibly Meacham-Winn syndromes. Simpson-Golabi-Behmel syndrome was felt to be the most likely diagnosis. If this opinion is correct, genital ambiguity, hydramnios and nephroblastomatosis should be added to the clinical spectrum of Simpson-Golabi-Behmel syndrome. Differential diagnosis between the above-mentioned syndromes is of major importance for accurate genetic counseling, considering the differences in recurrence risk. The present case underlines the need for long-term survey of patients suspected of having Simpson-Golabi-Behmel syndrome, who could be at risk for embryonic tumours.
Purpose: Familial clustering of abdominal aortic aneurysm was first noticed in 1977.
Methods: Through questionnaire and phone inquiry, familial data on 324 probands with abdominal aortic aneurysms ...allowed the establishment of 313 multigenerational pedigrees including 39 with multiple affected patients.
Results: There were 276 sporadic cases (264 men, 12 women); 81 cases belonged to multiplex pedigrees (76 men; 5 women). We compared familial and sporadic male cases; the ages at diagnosis were 64.1 ± 7.9 years and 66.0 ± 7.3 years (
p < 0.05), respectively, the ages at rupture were 65.4 ± 6.6 years and 75.2 ± 8.6 years (
p < 0.001), and the rupture rate was 32.4% and 8.7% (
p < 0.001). Survival curves were computed. Relative risk for male siblings of a male patient was 18. We performed a segregation analysis with the mixed model, the most likely explanation for occurrence of abdominal aortic aneurysm in our families was a single gene effect showing dominant inheritance. The frequency of the morbid allele was 1:250, and its age-related penetrance was not higher than 0.4.
Conclusion: This analysis indicates the preeminence of genetic factors on multifactorial/environmental effects of the pathogenesis of abdominal aortic aneurysm. (J V
ASC S
URG 1995;21:646-55.)
Inclusion of the BCR–ABL ES probe in routine cytogenetics led to the identification of a subgroup of Philadelphia positive (Ph+) chronic myeloid leukaemia patients characterized by a 5′‐ABL deletion. ...This anomaly was observed in 5/51 cases (9·8%). Cytological and clinical data suggest that the 5′‐ABL deletion may be associated with dysplastic features of polymorphonuclear cells and metamyelocytes and a short chronic phase duration.
In South Belgium (Wallonia), the 'triple test' was introduced in 1990-1991, and is nowadays a widely accepted screening method for assessment of trisomy21 risk in pregnancy. The 'triple test' is not ...regulated and can be freely performed by any biomedical lab, making epidemiological data unavailable. By contrast, cytogenetic investigations are limited to a few genetic centres, and accurate statistics can be easily built from their files. During the period 1984-1989, a total of 244trisomy21 (1/876 pregnancies) were diagnosed in the Genetic Centres of Liege and Loverval, 42 (17%) of them prenatally. During the period 1993-1998, 294trisomy21 (1/704 pregnancies) were observed, 165 (56%) of which prenatally, and more than 90% of affected pregnancies were terminated. Even after correction for late foetal loss of trisomic foetuses, the difference is highly significant, and corresponds to a theoretical shift in the incidence of trisomy21 at birth from 1/794 to 1/1606. As no remarkable progress occurred in other non-invasive prenatal screening procedures or general health care policies in Belgium, the most reasonable explanation is the use on a large scale of triple test by pregnant women, and the election of termination for most affected pregnancies. European Journal of Human Genetics (2001) 9, 1-4.
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