Clinical and molecular report of c.1331 + 1G > A mutation of the AAAS gene in a Moroccan family with Allgrove syndrome: a case report.

BACKGROUND: Allgrove syndrome is a rare autosomal recessive disorder characterized by the triad of achalasia, alacrimia and adrenal insufficiency. It is caused by the mutations of the AAAS gene located on chromosome 12q13. The c.1331 + 1G > A mutation is one of the most common described in North Africa including Tunisia, Algeria and Libya. We report here the clinical and genetic profile of a Moroccan family with Allgrove syndrome. CASE PRESENTATION: A Moroccan sister and brother born to consanguineous parents were found, at the ages of twelve and fifteen months old respectively, to have alacrimia and isolated glucocorticoid deficiency. Later, they developed achalasia whereupon Allgrove syndrome was diagnosed clinically and confirmed by DNA sequencing which revealed a c.1331 + 1G > A mutation in the AAAS gene. CONCLUSION: This finding reinforces previous studies in demonstrating the geographic expansion of the ancestral mutation c.1331 + 1G > A in North African patients and thus enabling targeted genetic counseling. To the best of our knowledge, this is the first report of the AAAS gene mutation in Moroccan patients.

A novel TRPS1 mutation in a Moroccan family with Tricho-rhino-phalangeal syndrome type III: case report.

BACKGROUND: Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, pear-shaped nose and cone shaped epiphyses. This condition is caused by haploinsufficiency of the TRPS1 gene. Previous genotype-phenotype studies have correlated exon 6 missense mutations with TRPS type III, a severe form of type I with pronounced, facial characteristics, short stature and brachydactyly and differing from type II by the absence of exostoses and mental retardation. CASE PRESENTATION: We report the first case of a Moroccan family, a father and his three children, in which the diagnosis of type III TRPS was suspected based on severe clinical and radiological features. Molecular analysis of the TRPS1 gene revealed a novel missense mutation in exon 6, (p.Ala932Ser), located in the GATA-type DNA-binding zinc finger domain. CONCLUSION: Our observations in this kindred support the previous genotype-phenotype results suggesting that patients with more pronounced facial characteristics and more severe shortening of hands and feet are more likely to have mutation in exon 6 of TRPS1.

Clinical and molecular report of novel GALC mutations in Moroccan patient with Krabbe disease: case report.

BACKGROUND: Krabbe disease (KD) or globoid cell leukodystrophy is an autosomal recessive lysosomal disorder, which affects metabolic and neurologic systems. This pathology has different forms. Infantile onset is about 85% to 90% of individuals with Krabbe disease. Disorder's onset is characterized, in early childhood, by hyperirritability, psychomotor deterioration associated to episodes of fever. To date, all reported cases have been attributed to mutations in galactosylceramidase gene (GALC gene) that encodes an enzyme which degrades galactosyl-sphingolipids (galactosylceramide, psychosine), essential in myelin production. A child compounded with two new mutations in the GALC gene was detected. CASE PRESENTATION: An eleven month old male child of Moroccan origin presented to our genetic consultation with severe symptoms that included hypotonia, fever, vision loss and feeding difficulties. He was suffering from the 4th month of life. Krabbe disease was suspected. Galactocerebrosidase deficiency was confirmed by biochemical analysis. DNA sequencing revealed a novel heterozygous compound mutation in GALC gene. The child was compounded with two mutations c.860G > A; p.Cys287Tyr and c.1622G > A; p.Trp541*. CONCLUSION: These new mutations could affect GALC structure and therefore its function. The identification of these mutations and their associated phenotypes are important to predict the prognosis and to confer to families an adequate genetic counseling.