Occurrence of Amyotrophic Lateral Sclerosis in Type 1 Gaucher Disease

ObjectiveTo report the association between type 1 Gaucher disease (GD1) and amyotrophic lateral sclerosis (ALS) in 3 unrelated families and to explore whether GBA variants influence the risk of ALS.MethodsWe conducted retrospective chart reviews of patients with GD1 or their family members diagnosed with ALS. To further investigate whether there is an association between ALS and GD, we performed exploratory analyses for the presence of GBA variants in 3 ALS cohorts from Toronto (Canada), Montreal (Canada), and Project MinE (international), totaling 4,653 patients with ALS and 1,832 controls.ResultsWe describe 2 patients with GD1 and 1 obligate GBA mutation carrier (mother of GD1 patient) with ALS. We identified 0 and 8 GBA carriers in the Toronto and Montreal cohorts, respectively. The frequencies of GBA variants in patients with ALS in the Montreal and Project MinE cohorts were similar to those of Project MinE controls or Genome Aggregation Database population controls.ConclusionsThe occurrence of ALS in biallelic or monoallelic GBA mutation carriers described here, in addition to common pathogenic pathways shared by GD1 and ALS, suggests that GBA variants could influence ALS risk. However, analyses of GBA variants in ALS cohorts did not reveal a meaningful association. Examination of larger cohorts and neuropathologic studies will be required to elucidate whether patients with GD1 are indeed at increased risk for ALS.

Defining the molecular pathology and consequent phenotypes in Egyptian HB patients

Background Hemophilia B (HB) (also known as Christmas disease) is a rare X-linked recessive disorder characterized by spontaneous or prolonged hemorrhages caused by mutations in Factor 9 (F9) gene leading to deficient or defective coagulation F9. Our study aimed at identifying the causative mutations within a sample of HB Egyptian patients. The present study comprised clinical data of eleven HB patients descending from six unrelated families and a seventh family including a carrier mother with a history of deceased HB sibling. Sequencing of F9 gene was performed. Results The study revealed four mutations; two missense NM_000133.3:c.676C>G, (P.Arg226Gly) and NM_000133.3:c.1305T>G, (p.Cys435Trp), and two nonsense mutations NM_000133.3:c.880C>T, (p.Arg294*) and NM_000133.3:c.1150C>T, (p.Arg384*), identified mutations spanned exons 6 and 8 of which a total of three mutations are located in hotspot exon 8 of F9 gene. Conclusions Reviewing the literature, this is the first molecular analysis of F9 gene in HB Egyptian patients. Consistent genotype/phenotypic severity correlation could be concluded, helping proper genetic counseling and prenatal decision taking.

Identification of Factor VII Gene Mutations in Patients with Haemophilia A

The study is aimed to detect the primary mutations of the FVIII gene among Iraqi patients using molecular analysis and to identify the relationships between these mutations and the severity of the disease. The study involved twenty-five patients with haemophilia type A, eighteen of those patients were males, and seven of them were mothers with disease carriers, from seven families but un-related. The extracted DNA determined by the concentration and purity and then after the amplification of selected parts of the FVIII gene involving intron 22 and exons 18, 22, 23, 24 were done. Sequencing of these exons and introns were done for all patients and control subjects. Sequencing analysis showed that the majority of mutations were "point mutations" in exons, mostly in exon 24. In contrast, the mutations in exon 18 were identified in one male in addition to one carrier mother. The mutations in exon 22 were identified in four patients, and the mutation in exon 23 was identified in two males in addition to two carrier mothers. The mutations in exon 24 were identified in twelve patients with haemophilia in addition to two carrier mothers. Moreover, the numbers of identified inversion mutations in the study were seven in hemophilic patients. The study showed there was a direct relationship between the severity of disease and the mutations in exon 24 and intron 22. So, the ultimate conclusion of this study showed that the most common mutations in Iraqi hemophilic patients were exon 24 mutations and followed by intron 22 mutations. The majority of these mutations occurred in severe cases of haemophilia.

Jacobsenov sindrom

Jacobsen syndrome is a gene syndrome caused by partial deletion of the long arm of chromosome 11.About 20% of children die during the first two years of life, most commonly realated to complications from congenital heart disease, less commonly from bleeding.The authors present a male newborn that inhereted unbalanced deletion from a carrier mother.

Cytogenetic profile of Down syndrome in Alexandria, Egypt

During 1992-2001, 673 Down syndrome patients were referred to the Department of Human Genetics in Alexandria. Regular [free] trisomy 21 constituted 95.4% of cases; Robertsonian translocation 2.7%; and mosaicism 0.7%. In 8 cases, regular trisomy 21 was associated with structural or numerical chromosome anomalies. Translocation was parentally inherited for 33.3% of cases and maternal transmission was twice as common as paternal. Two translocated Down syndrome fetuses were diagnosed prenatally in at [14; 21] carrier mother. Mean maternal age was high in regular trisomy 21 [38.2 years] but not in translocation [25.3 years]. There was an excess of males in all groups except the mosaic group where the male: female ratio was 0.67. Cytogenetic investigations assist in patient management and family counselling