Genetic counseling in carriers of reciprocal translocations involving two autosomes.

One of the main genetic causes involve in the pathogenesis of recurrent abortion is parental chromosomal abnormalities. The central concept in genetic counseling with such families is to estimate the probability of recurrence of unfavorable pregnancy outcomes. The main questions that consultants usually ask are: Why did this happen? What is the risk to be done again?Our cases were two families with repeated miscarriage. The pedigrees were drawn, the chromosomes of couples were studied, and estimation for recurrent risk was done. We tried to answer those two main questions and clear the results for them.Parental chromosome abnormalities were founded after karyotyping with GTG technique at 450 band resolution, revealing 46 chromosomes with balanced translocation of autosomes in one of the partner in both families. Recurrent risk was estimated as "high" for their future pregnancies in each family.Couples in which one partner is the carrier of such balanced translocation have increased risks of infertility, recurrent abortion, and delivery of chromosomally abnormal offspring. Genetic counseling of such couples, therefore, presents a unique challenge and should be considered in dealing with such families.

A survey of (CAG)n repeats causing juvenile Huntington disease in an Iranian family with 4 affected members.

Huntington's disease is caused by a trinucleotide repeat expansion (CAG)n in the gene coding for Huntingtin (Htt) and is one of the several polyglutamine diseases. Its physical symptoms occur in a large range of ages, with a mean occurrence in a person's late 40's and early 50's. Almost all references indicated that if the age of onset is below 20 years then it is known as juvenile HD. Our case was an Iranian family with 4 affected siblings (2 sisters and 2 brothers). In addition to 4 affected children, they had 5 normal male progenies. There was no any other case in their family history. The onset age of the disease in our case family was 20 to 25 years. Their parents were unaffected and nonconsanguineous. Analysis of the pathogenic (CAG)n repeat region of the HD gene for the affected members have showed an expansion allele with 46, 50, 46, and 44 repeats in 4 affected siblings. Our results indicated that the age of 20 years maybe is not a stable limit point for all cases of juvenile HD, and perhaps onset ages are related with the CAG repeat sizes in such individuals.

High carrier frequency of the GJB2 mutation (35delG) in the north of Iran.

OBJECTIVE: Mutations in the GJB2 gene are a major cause of autosomal recessive and sporadic non-syndromic hearing loss in many populations. A single mutation of this gene (35delG) accounts for approximately 70% of mutations in Caucasians with a carrier frequency of 2-4% in Europe. This study aims to determine the rate of 35delG carrier frequency in Iran. METHODS: Genomic DNA was extracted from a total of 550 unaffected unrelated subjects from 4 provinces of Iran following the standard phenol chloroform procedure. The one base pair deletion (35delG) was analysed using a nested PCR procedure; 35delG mutation carriers were subsequently confirmed by sequence analysis. Moreover, using the Binomial probability distribution, we compared the 35delG carrier frequency of Iranian population with the various Middle Eastern and overall European populations. RESULTS: Of the four populations studied, we found a high carrier frequency of 2.8% in Gilan province in the north of Iran. The overall 35delG carrier frequency was found to be 1.25% in the populations studied (our present and previous data) which is similar to the overall 35delG carrier frequency detected in Middle Eastern populations, but Significantly lower than that identified in European populations.

Homozygous missense mutation in fibulin-5 in an Iranian autosomal recessive cutis laxa pedigree and associated haplotype.

Cutis laxa is a rare group of inherited and acquired disorders characterized by loose and redundant skin with reduced elasticity. Mutations in the elastin coding gene have been shown to cause autosomal dominant cutis laxa in three families. A homozygous mutation in the fibulin-5 coding gene was discovered in a Turkish pedigree showing recessive inheritance, and a different mutation in this gene was found in the heterozygous state in a sporadic case of the disease. Here, we report the third case of a mutation in the fibulin-5 coding gene in a recessive Iranian cutis laxa pedigree. The mutation is the same as previously reported in the Turkish pedigree, further confirming that it is causative of disease. A haplotype consisting of seven intragenic sequence variations common to both pedigrees is described for the mutation-carrying fibulin-5 allele.