Lm. Brzustowicz et al., PATERNAL ISODISOMY FOR CHROMOSOME-5 IN A CHILD WITH SPINAL MUSCULAR-ATROPHY, American journal of human genetics, 54(3), 1994, pp. 482-488
Paternal isodisomy for chromosome 5 was detected in a 2-year-old boy w
ith type III spinal muscular atrophy (SMA), an autosomal recessive deg
enerative disorder of alpha motor neurons, known to map to 5q11.2-13.3
. Examination of 17 short-sequence repeat polymorphisms spanning 5p15.
1-15.3 to 5q33.3-qter produced no evidence of maternally inherited all
eles. Cytogenetic analysis revealed a normal male karyotype, and FISH
with probes closely flanking the SMA locus confirmed the presence of t
wo copies of chromosome 5. No developmental abnormalities, other than
those attributable to classical childhood-onset SMA, were present. Whi
le the absence of a maternally derived chromosome 5 could have produce
d the symptoms of SMA through the mechanism of genomic imprinting, the
lack of more global developmental abnormalities would be unusual. Pat
ernal transmission of two copies of a defective gene at the SMA locus
seems to be the most likely cause of disease, but proof of this will h
ave to await the identification of the SMA gene. While uniparental iso
disomy is a rare event, it must be considered as a possible mechanism
involved in SMA when conducting prenatal testing and counseling for th
is disorder.