Introduction. - X-linked adrenoleukodystrophy (ALD) is the most frequent type of leukodystrophy (1/17 000 males). The phenotypic range in male patients varies from the severe cerebral presentations in children to the ...Introduction. - X-linked adrenoleukodystrophy (ALD) is the most frequent type of leukodystrophy (1/17 000 males). The phenotypic range in male patients varies from the severe cerebral presentations in children to the milder myeloneuropathy and to isolate adrenal insufficiency. More than a half of the carrier females display clinical symptoms over the age of 40 years. Observation. - Diagnosis of ALD was raised in a 40 year-old female who presented with spastic paraparesis and sphincterian dysfunction, occurring after the delivery of her first child. There was no family history of ALD. Very long-chain fatty acids (VLCFA) were assayed in her one-year-old son in order to propose appropriate hormonal and neurological survey. His dosage was abnormal and an adrenal insufficiency was subsequently found. A brain MRI will be proposed biannually when he reaches to age of for years. The proband’s mother had an increased level of VLCFA, showing that she was a carrier. Family screening was extended to the proband’s sisters and maternal aunt who already had children, but also to her brother, who may express a mild form of the disease later on, and to her maternal uncles who might be asymptomatic carriers. A frameshift mutation was found in the ABCD1 gene and will allow accurate carrier identification and prenatal diagnosis in the family. Conclusion. - ALD diagnosis should be evoked in a woman affected by myelopathy despite the lack of family history. Such a diagnosis has severe consequences since some of the related males may carry the mutation although they do not display any symptom at time of diagnosis, and because carrier females have a risk to both have a clinical expression of the disease and give birth to an affected boy.展开更多
The authors found a correlation between the age at which probands experience a n incident stroke and the age at which their siblings experience an incident str oke (r=0.68; p < 0.0001). Proband-sibling incident str...The authors found a correlation between the age at which probands experience a n incident stroke and the age at which their siblings experience an incident str oke (r=0.68; p < 0.0001). Proband-sibling incident stroke latency correlations were observed in analyses restricted to siblings concordant for smoking (r=0.68; p < 0.0001), diabetes (r=0.73; p < 0.0001),and hypertension (r=0.63; p < 0.0001 ). In the authors’cohort of affected sibling pairs, inherited factors were impo rtant determinants of incident ischemic stroke latency.展开更多
PURPOSE: To compare age-related macular degeneration (AMD)phenotypebetween probands in singleton andmultiplex families to determine whether data from these two groups may be combined for consolidated genetic analyses....PURPOSE: To compare age-related macular degeneration (AMD)phenotypebetween probands in singleton andmultiplex families to determine whether data from these two groups may be combined for consolidated genetic analyses. DESIGN: Retrospective case-control study. METHODS: Individuals 55 years of age or older with AMD were identified. Complete histories and examinations were recorded, 35-mm fundus photographs obtained, and macular findings graded. Detailed information was recorded, including the presence of extramacular and peripheral drusen, peripheral reticular pigmentary change, posterior vitreous detachment, and iris color. Comparisons were performed between probands from singleton and multiplex families. RESULTS: There was no statistically significant difference in grade between the 411 singleton and 125 multiplex probands (P=.52), and the distribution of grades was similar between the two groups. No statistically significant difference was found between proband groups with respect to the presence or extent of small (P=.48), intermediate (P=.72), and large drusen (P=.74) and retinal pigment epitheliumhyper-(P=.76) and hypopigmentation (P=.55); in the presence or grade of peripheral reticular pigment change; the presence of geographic atrophy in exudative disease, extramacular drusen, or posterior vitreous detachment; lens status; iris color; visual acuity; intraocular pressure; optic nerve cupping; and body mass index. A statistically significant difference between the two groups was noted in the presence of peripheral drusen (P= .0001). CONCLUSIONS: Singleton and multiplex AMD probands share a similar phenotype. This suggests that multiplex and singleton data can be combined for consolidated genetic analyses.展开更多
文摘Introduction. - X-linked adrenoleukodystrophy (ALD) is the most frequent type of leukodystrophy (1/17 000 males). The phenotypic range in male patients varies from the severe cerebral presentations in children to the milder myeloneuropathy and to isolate adrenal insufficiency. More than a half of the carrier females display clinical symptoms over the age of 40 years. Observation. - Diagnosis of ALD was raised in a 40 year-old female who presented with spastic paraparesis and sphincterian dysfunction, occurring after the delivery of her first child. There was no family history of ALD. Very long-chain fatty acids (VLCFA) were assayed in her one-year-old son in order to propose appropriate hormonal and neurological survey. His dosage was abnormal and an adrenal insufficiency was subsequently found. A brain MRI will be proposed biannually when he reaches to age of for years. The proband’s mother had an increased level of VLCFA, showing that she was a carrier. Family screening was extended to the proband’s sisters and maternal aunt who already had children, but also to her brother, who may express a mild form of the disease later on, and to her maternal uncles who might be asymptomatic carriers. A frameshift mutation was found in the ABCD1 gene and will allow accurate carrier identification and prenatal diagnosis in the family. Conclusion. - ALD diagnosis should be evoked in a woman affected by myelopathy despite the lack of family history. Such a diagnosis has severe consequences since some of the related males may carry the mutation although they do not display any symptom at time of diagnosis, and because carrier females have a risk to both have a clinical expression of the disease and give birth to an affected boy.
文摘The authors found a correlation between the age at which probands experience a n incident stroke and the age at which their siblings experience an incident str oke (r=0.68; p < 0.0001). Proband-sibling incident stroke latency correlations were observed in analyses restricted to siblings concordant for smoking (r=0.68; p < 0.0001), diabetes (r=0.73; p < 0.0001),and hypertension (r=0.63; p < 0.0001 ). In the authors’cohort of affected sibling pairs, inherited factors were impo rtant determinants of incident ischemic stroke latency.
文摘PURPOSE: To compare age-related macular degeneration (AMD)phenotypebetween probands in singleton andmultiplex families to determine whether data from these two groups may be combined for consolidated genetic analyses. DESIGN: Retrospective case-control study. METHODS: Individuals 55 years of age or older with AMD were identified. Complete histories and examinations were recorded, 35-mm fundus photographs obtained, and macular findings graded. Detailed information was recorded, including the presence of extramacular and peripheral drusen, peripheral reticular pigmentary change, posterior vitreous detachment, and iris color. Comparisons were performed between probands from singleton and multiplex families. RESULTS: There was no statistically significant difference in grade between the 411 singleton and 125 multiplex probands (P=.52), and the distribution of grades was similar between the two groups. No statistically significant difference was found between proband groups with respect to the presence or extent of small (P=.48), intermediate (P=.72), and large drusen (P=.74) and retinal pigment epitheliumhyper-(P=.76) and hypopigmentation (P=.55); in the presence or grade of peripheral reticular pigment change; the presence of geographic atrophy in exudative disease, extramacular drusen, or posterior vitreous detachment; lens status; iris color; visual acuity; intraocular pressure; optic nerve cupping; and body mass index. A statistically significant difference between the two groups was noted in the presence of peripheral drusen (P= .0001). CONCLUSIONS: Singleton and multiplex AMD probands share a similar phenotype. This suggests that multiplex and singleton data can be combined for consolidated genetic analyses.
