12.18
Malattie legate al sesso
Come gli autosomi, i cromosomi sessuali contengono una varietà di geni necessari per la normale funzione corporea. Quando una mutazione in uno di ques…
- [Relatore] Alcune malattie ereditarie
sono causate da mutazioni di un singolo gene.
E quando si trovano su un cromosoma sessuale,
la malattia si definisce "sex-linked".
In base al cromosoma sessuale sul quale il gene si colloca
e a seconda del fatto che una o due copie siano necessarie
per il corretto funzionamento,
tali malattie si definiscono Y-linked,
X-linked dominanti o X-linked recessive.
Le prime, le malattie Y-linked come l'infertilità del
cromosoma Y sono causate da mutazioni dei geni posti sul
cromosoma Y e si trasmettono solo da padre a figlio.
Le seconde, le malattie X-linked dominanti
come la sindrome dell'X fragile
richiedono una sola copia del gene mutato,
possono colpire sia i maschi che le femmine
e non si trasmettono da padre a figlio.
Infine, le malattie X-linked recessive
colpiscono più i maschi, perché
nelle femmine sono necessarie 2 copie del gene mutato.
Però le femmine eterozigoti sane possono essere portatrici e
hanno il 50% di probabilità di passare la malattia ai figli.
Ad esempio, una malattia X-linked recessiva
chiamata Distrofia Muscolare di Duchenne, DMD
colpisce quasi esclusivamente i maschi.
La DMD è causata da mutazioni del gene che codifica per la
distrofina, la proteina che contribuisce alla
corretta contrazione e riparazione delle cellule
muscolari scheletriche e cardiache.
Tali mutazioni possono portare a cambiamenti
strutturali e funzionali della proteina distrofina
senza la quale le cellule muscolari si indeboliscono
fino ad atrofizzarsi.
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Q1: What are the three main types of sex-linked disorders?
Sex-linked disorders fall into three categories based on their chromosomal location and inheritance pattern. Y-linked disorders affect only males and pass from father to son. X-linked dominant disorders require one mutated copy and affect both sexes, though males may be more severely impacted. X-linked recessive disorders require two mutated copies in females but only one in males, making males more frequently affected.
Q2: Why do X-linked recessive disorders affect males more often than females?
Males have only one X chromosome, so a single mutated gene causes the disorder. Females have two X chromosomes and need mutations on both copies to display the condition. This genetic difference means males are affected more frequently by X-linked recessive disorders like color blindness, hemophilia, and Duchenne muscular dystrophy.
Q3: What is Duchenne muscular dystrophy and how does it develop?
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the gene encoding dystrophin, a protein essential for muscle contraction and repair. Without functional dystrophin, skeletal and cardiac muscle cells weaken and gradually atrophy. DMD almost exclusively affects boys and results from structural or functional changes to the dystrophin protein.
Q4: Can carrier mothers pass X-linked recessive disorders to their children?
Unaffected heterozygous carrier mothers have a 50% chance of passing an X-linked recessive mutation to each son, who will be affected. Daughters who inherit the mutation become carriers like their mother. Carrier status allows mothers to transmit the disorder without displaying symptoms themselves, making pedigree analysis and disease inheritance crucial for genetic counseling.
Q5: How do X-linked dominant disorders differ from X-linked recessive ones?
X-linked dominant disorders require only one mutated copy to cause the disorder and affect both males and females. X-linked recessive disorders require two mutated copies in females but only one in males. Fragile X syndrome, an X-linked dominant condition, causes developmental problems including learning disabilities and often affects males more severely than females.
Q6: What causes Y-linked disorders and how are they inherited?
Y-linked disorders result from mutations on genes located on the Y chromosome. These disorders can only pass from father to son since only males carry the Y chromosome. Y-chromosome infertility, caused by deletions in azoospermia factor (AZF) regions, exemplifies this pattern, though affected males typically require assisted reproductive technologies to father children.
Q7: Why can fathers with X-linked dominant disorders never pass the condition to their sons?
Fathers pass their Y chromosome to sons and their X chromosome to daughters. Males with X-linked dominant disorders have a mutated X chromosome, which they pass only to daughters, not sons. Sons receive the Y chromosome from their father, so they cannot inherit the X-linked mutation, preventing father-to-son transmission of X-linked dominant conditions.