A B3GALT6 variant in patient originally described as Al-Gazali syndrome and implicating the endoplasmic reticulum quality control in the mechanism of some ß3GalT6-pathy mutations.

Al-Gazali syndrome encompasses several clinical features including prenatal growth retardation, large joints contractures with camptodactyly, bilateral talipes equinovarus, small mouth, anterior segment anomalies of the eyes, and early lethality. Recently, a baby with features very similar to Al-Gazali syndrome was found to have compound heterozygous variants in B3GALT6. This gene encodes Beta-1,3-galactosyltransferase 6 (ß3GalT6), an essential component of the glycosaminoglycan synthesis pathway. Pathogenic variants in B3GALT6 have also been shown to cause Ehlers-Danlos syndrome spondylodysplastic type (spEDS-B3GALT6) and spondyloepimetaphyseal dysplasia with joint laxity type I (SEMD-JL1). In 2017, a new international classification of EDS included these 2 conditions together with the child reported to have features similar to Al-Gazali syndrome under spondylodysplastic EDS (spEDS). We report a disease-causing variant c.618C > G, p.(Cys206Trp) in 1 patient originally described as Al-Gazali syndrome and reported in 1999. We evaluated the involvement of the endoplasmic reticulum-associated protein degradation, in the pathogenesis of 13 B3GALT6 variants. Retention in endoplasmic reticulum was evident in 6 of them while the c.618C > G, p.(Cys206Trp) and the other 6 variants trafficked normally. Our findings confirm the involvement of B3GALT6 in the pathogenesis of Al-Gazali syndrome and suggest that Al-Gazali syndrome represents the severe end of the spectrum of the phenotypes caused by pathogenic variants in this gene.

A Novel Aberrant Splice Site Mutation in RAB23 Leads to an Eight Nucleotide Deletion in the mRNA and Is Responsible for Carpenter Syndrome in a Consanguineous Emirati Family.

Carpenter syndrome is caused by mutations in the RAB23 gene that encodes a small GTPase of the Rab subfamily of proteins. Rab proteins are known to be involved in the regulation of cellular trafficking and signal transduction. Currently, only few mutations in RAB23 have been reported in patients with Carpenter syndrome. In this paper, we report the clinical features, molecular and functional analysis of 2 children from an Emirati consanguineous family with this syndrome. The affected children exhibit the typical features including craniosynostosis, typical facial appearance, polysyndactyly, and obesity. Molecular analysis of the RAB23 gene revealed a homozygous mutation affecting the first nucleotide of the acceptor splice site of exon 5 (c.482-1G>A). This mutation affects the authentic mRNA splicing and activates a cryptic acceptor site within exon 5. Thus, the erroneous splicing results in an eight nucleotide deletion, followed by a frameshift and premature termination codon at position 161 (p.V161fsX3). Due to the loss of the C-terminally prenylatable cysteine residue, the truncated protein will probably fail to associate with the target cellular membranes due to the absence of the necessary lipid modification. The p.V161fsX3 extends the spectrum of RAB23 mutations and points to the crucial role of prenylation in the pathogenesis of Carpenter syndrome within this family.

[Breast cancer in Tunisia: clinical and epidemiological study]. / Le cancer du sein en Tunisie: étude clinique et épidémiologie.

This study has been realized to determine epidemiological profile and clinicopathologic aspect of breast cancer in Tunisia. We have counted and analyzed all cancers of the breast diagnosed in Tunisia with proof pathologic or to defect cytologic of malignancy, between first January 1994 and 31 December 1994. In the course of this year, 689 new cases of mammary cancers have been diagnosed at the women. The average patient age was 50.0 years, the incidence standardized on the age of the cancer of the breast in Tunisia was 16.7/100,000 women. The average size of the tumor was 49.5 mm (35.8 mm at patients processed in private clinics and 50.7 mm at patients processed in the public hospitals). According to TNM classification of 1988, 7.2% of tumors were classified T1, 48.9% T2, 18.5% T3, and 23.4% T4 (6.2% T4d and 16.1% T4b). 22.1% of tumors were M1. 3.3% were in situ carcinoma. For the infiltrants cancers, the grade II SBR has been the most frequent (53.6%). On the therapeutic plan, the conservative processing has been practiced only at 17.6% of patients. The cancer of the breast in Tunisia rest again relatively little frequent, and its clinic profile resides alarming. The inflammatory cancer notion of the breast (equal T4d) intimately linked to Tunisia overestimates probably the reality. Cancers that were classified "PEV" in many publications would be in reality only for most of locally evolved and neglected cancers.