PATERNAL ISODISOMY FOR CHROMOSOME-5 IN A CHILD WITH SPINAL MUSCULAR-ATROPHY

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.