Canavan disease: an Arab scenario.

The autosomal recessive Canavan disease (CD) is a neurological disorder that begins in infancy. CD is caused by mutations in the gene encoding the ASPA enzyme. It has been reported with high frequency in patients with Jewish ancestry, and with low frequency in non-Jewish patients. This review will shed light on some updates regarding CD prevalence and causative mutations across the Arab World. CD was reported in several Arab countries such as Saudi Arabia, Egypt, Jordan, Yemen, Kuwait, and Tunisia. The population with the highest risk is in Saudi Arabia due the prevalent consanguineous marriage culture. In several studies, four novel mutations were found among Arabian CD patients, including two missense mutations (p.C152R, p.C152W), a 3346bp deletion leading to the removal of exon 3 of the ASPA gene, and an insertion mutation (698insC). Other previously reported mutations, which led to damage in the ASPA enzyme activities found among CD Arab patients are c.530 T>C (p.I177T), c.79G>A (p.G27R), IVS4+1G>T, and a 92kb deletion, which is 7.16kb upstream from the ASPA start site. This review will help in developing customized molecular diagnostic approaches and promoting CD carrier screening in the Arab world in areas where consanguineous marriage is common particularly within Saudi Arabia.

Assessing ethnicity in preconception counseling: genetics--what nurse practitioners need to know.

PURPOSE: To define and discuss five genetic disorders--Tay-Sachs, sickle cell anemia, Canavan's disease, thalassemia, and cystic fibrosis (CF)--and to explain the importance of the nurse practitioner's (NP's) assessment of clients' ethnicity during preconception counseling, which should address these genetic conditions. DATA SOURCES: Review of literature from professional journals, professional organizations' Web sites, guidelines from the American College of Obstetricians and Gynecologists, the National Institute of Health Consensus Statement, and the authors' professional clinical experience. CONCLUSIONS: The goal of preconception counseling is to identify potential or actual medical, psychological, or social conditions that may affect the mother or fetus. NPs are often the health care providers that initiate preconception counseling to women in varied primary care settings. NPs must be familiar with ethnicity-related inheritable conditions in order to provide appropriate client information and education and to implement testing and, when needed, referral for genetic counseling to individuals and families at risk for genetic disorders such as Tay-Sachs, Canavan's disease, CF, sickle cell anemia, and thalassemia. IMPLICATIONS FOR PRACTICE: NPs providing health care to women of child-bearing age should assess the client's use of contraception and intent for future pregnancy. Preconception counseling when indicated should be initiated to all women to increase their potential for healthy pregnancy outcomes. Although a comprehensive personal, family, medical, and psychosocial history and initiation of folic acid are the mainstays of preconception counseling, assessment for risk of ethnicity-related genetic conditions must also be included in prepregnancy health care.

Canavan disease: mutations among Jewish and non-Jewish patients.

Canavan disease is an autosomal recessive leukodystrophy caused by the deficiency of aspartoacylase (ASPA). Sixty-four probands were analyzed for mutations in the ASPA gene. Three point mutations--693C-->A, 854A-->C, and 914C-->A--were identified in the coding sequence. The 693C-->A and 914C-->A base changes, resulting in nonsense tyr231-->ter and missense ala305-->glu mutations, respectively, lead to complete loss of ASPA activity in in vitro expression studies. The 854A-->C transversion converted glu to ala in codon 285. The glu285-->ala mutant ASPA has 2.5% of the activity expressed by the wild-type enzyme. A fourth mutation, 433 --2(A-->G) transition, was identified at the splice-acceptor site in intron 2. The splice-site mutation would lead to skipping of exon 3, accompanied by a frameshift, and thus would produce aberrant ASPA. Of the 128 unrelated Canavan chromosomes analyzed, 88 were from probands of Ashkenazi Jewish descent. The glu285-->ala mutation was predominant (82.9%) in this population, followed by the tyr231-->ter (14.8%) and 433 --2(A-->G) (1.1%) mutations. The three mutations account for 98.8% of the Canavan chromosomes of Ashkenazi Jewish origin. The ala305-->glu mutation was found exclusively in non-Jewish probands of European descent and constituted 60% of the 40 mutant chromosomes. Predominant occurrence of certain mutations among Ashkenazi Jewish and non-Jewish patients with Canavan disease would suggest a founding-father effect in propagation of these mutant chromosomes.