ABSTRACT
Genetic diseases in the Tunisian population represent a real problem of public health as their spectrum encompasses more than 400 disorders. Their frequency and distribution in the country have been influenced by demographic, economic and social features especially consanguinity. In this article, we report on genetic disease association referred to as comorbidity and discuss factors influencing their expressivity. Seventy-five disease associations have been reported among Tunisian families. This comorbidity could be individual or familial. In 39 comorbid associations, consanguinity was noted. Twenty-one founder and 11 private mutations are the cause of 34 primary diseases and 13 of associated diseases. As the information dealing with this phenomenon is fragmented, we proposed to centralize it in this report in order to draw both clinicians' and researcher's attention on the occurrence of such disease associations in inbred populations as it makes genetic counseling and prenatal diagnosis challenging even when mutations are known.
Subject(s)
Consanguinity , Genetic Diseases, Inborn/epidemiology , Comorbidity , Female , Founder Effect , Genetic Diseases, Inborn/genetics , Humans , Male , Pedigree , Tunisia/epidemiologyABSTRACT
Sanjad-Sakati syndrome (SSS) (OMIM 241410) is a rare autosomal recessive disorder characterized by congenital hypoparathyroidism with growth and mental retardation associated with seizures and a characteristic physiognomy. SSS molecular pathology has been shown to be due to mutations in the TBCE gene on chromosome 1q42-q43. All affected patients of Arab origin are homozygous for a 12-bp (155-166del) deletion in exon 3 of this gene. We report on a Tunisian child with SSS who was homozygous for the 155-166del mutation. Our findings provide additional support of the common (155-166del) deletion founder effect in exon 3 of the TBCE gene in Arab patients. It is very likely that this mutation originated in the Middle East and was introduced in Tunisia by the Banu Hilal invaders.
Subject(s)
Abnormalities, Multiple/genetics , Exons , Face/abnormalities , Growth Disorders/genetics , Hypoparathyroidism/genetics , Infant, Premature , Intellectual Disability/genetics , Molecular Chaperones/genetics , Mutation , Osteochondrodysplasias/genetics , Seizures/genetics , Abnormalities, Multiple/diagnosis , Biomarkers/metabolism , Female , Growth Disorders/diagnosis , Humans , Hypoparathyroidism/diagnosis , Infant, Newborn , Intellectual Disability/diagnosis , Osteochondrodysplasias/diagnosis , Premature Birth , Seizures/diagnosis , TunisiaABSTRACT
OBJECTIVE: The present study is aimed at performing the molecular characterization of a Tunisian family with piebaldism. METHODS: As the proband and her mother showed a severe phenotype, we first chose to screen exons 10, 11, 12, 13, 16, 17 and 18 of the KIT proto-oncogene by direct sequencing. RESULTS: Direct sequencing analysis showed a C to T substitution at 1939 in exon 13 (c.1939C>T) in heterozygous state in the patient and her mother. The mutation was not found in their unaffected family members or normal controls. CONCLUSION: Our results provide additional support that mutations in the tyrosine kinase domain of the KIT gene are responsible for the severe form of piebaldism.
Subject(s)
Mutation, Missense , Piebaldism/genetics , Point Mutation , Proto-Oncogene Proteins c-kit/genetics , Amino Acid Substitution , Catalytic Domain , Exons/genetics , Female , Humans , Infant , Male , Phenotype , Protein Structure, Tertiary , Proto-Oncogene Mas , Sequence Analysis, DNA , TunisiaABSTRACT
Maple syrup urine disease (MSUD) is a rare disorder of branched-chain amino acids (BCAA) metabolism caused by the defective function of branched-chain α-ketoacid dehydrogenase complex (BCKD). The disease causal mutations can occur either in BCKDHA, BCKDHB or DBT genes encoding respectively the E1α, E1ß and E2 subunits of the complex. In this study we report the molecular characterization of 3 Tunisian patients with the classic form of MSUD. Two novel putative mutations have been identified: the alteration c.716A>G (p.Glu239Gly) in BCKDHB and a small deletion (c.1333_1336delAATG; p.Asn445X) detected in DBT gene.
