مواضيع المحاضرة: X-linked recessive inheritance
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Fifth stage 

Pediatric 

Lec-9

 

أوس

 

7/3/2016

 

 

X-linked recessive inheritance 

Over 400 disorders have been described in which an abnormal recessive gene is carried on 
the X chromosome  

 

1.  males are affected  

2.  occasionally a female carrier shows mild signs of the disease (manifesting carrier)  

3.  each son of a female carrier has a 1 in 2 (50%) risk of being affected  

4.  each daughter of a female carrier has a 1 in 2 (50%) risk of being a carrier  

5.  daughters of affected males will all be carriers  

6.  sons of affected males will not be affected, since a man passes a Y chromosome to his 
son 

 


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SUMMARY: 

1. males are affected; females can be carriers but are usually healthy or have mild 
disease   

2. family history may be negative - new mutations and gonadal mosaicism    

3. identifying female carriers is important to be able to provide genetic counselling 

 

X-linked dominant inheritance: 

In which female carriers typically manifest abnormal findings. An affected man will have 
only affected daughters and unaffected sons, and half of the offspring of an affected 
woman will be affected .  

Some X-linked dominant conditions are lethal in males. An example is incontinentia 
pigmenti. 

 

 

 


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Chromosomal abnormalities: 

 

Chromosomal abnormalities are either numerical or structural. They occur in 
approximately 10% of spermatozoa and 25% of mature oocytes and are a very common 
cause of early spontaneous miscarriage 

 

The estimated incidence of chromosomal abnormalities in live-born infants is about 1 
in 150 and these usually, but not always, cause multiple congenital anomalies and 
learning difficulties. Acquired chromosomal changes play a significant role in 
carcinogenesis and tumour progression.  

 

Down's syndrome (trisomy 21) 

 

This is the most common autosomal trisomy and the most common genetic cause of 
severe learning difficulties. The incidence in live-born infants is about 1 in 650.  

 

Cytogenetics 

 

The extra chromosome 21 may result from non-disjunction, translocation or   

 

Mosaicism 

 

Non-disjunction (94%) 

most cases result from an error at meiosis  

the pair of chromosome 21s fails to separate, so that one gamete has two chromosome 21s 
and one has none  

fertilisation of the gamete with two chromosome 21s gives rise to a zygote with trisomy 21  

parental chromosomes do not need to be examined.  

 


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Translocation (5%) 

When the extra chromosome 21 is joined onto another chromosome (usually chromosome 
14, but occasionally chromosome 15, 22 or 21), this is known as an unbalanced 
Robertsonian translocation. An affected child has 46 chromosomes, but three copies of 
chromosome 21 material. In this situation, parental chromosomal analysis is essential since 
one of the parents carries a balanced translocation in 25% of cases. Translocation carriers 
have 45 chromosomes, one of which consists of the two joined chromosomes  

 

 

the risk of recurrence is 10-15% if the mother is the translocation carrier and about 2.5% if 
the father is the carrier  

if a parent carries the rare 21:21 translocation, all the offspring will have Down's syndrome  

if neither parent carries a translocation (75% of cases), the risk of recurrence is <1%.  

 

 

Mosaicism (1%) 

In mosaicism some of the cells are normal and some have trisomy 21. This usually arises 
after the formation of the zygote, by non-disjunction at mitosis. The phenotype may be 
milder in mosaicism.  

 




رفعت المحاضرة من قبل: Abdalmalik Abdullateef
المشاهدات: لقد قام 44 عضواً و 237 زائراً بقراءة هذه المحاضرة








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