A splice junction mutation in intron 2 of the carbonic anhydrase II gene of osteopetrosis patients from Arabic countries

Hum Mutat. 1992;1(4):288-92. doi: 10.1002/humu.1380010404.


Clinical manifestations in patients with carbonic anhydrase (CA) II deficiency include osteopetrosis, renal tubular acidosis, and cerebral calcification. Of the 39 reported cases of the carbonic anhydrase II deficiency syndrome, 72% were patients from North African and Middle Eastern countries, most, if not all, of whom were of Arabic descent. We have analyzed DNAs from members of six unrelated Arabic kindreds and found five to be homozygous and one heterozygous for a novel splice junction (donor site) mutation at the 5' end of intron 2. These findings suggest that a common "Arabic" mutation may be the predominant cause of CA II deficiency in this region. The mutation introduces a new Sau3A1 restriction site which allows polymerase chain reaction (PCR)-based diagnosis of this mutation that should be useful in diagnosis, carrier detection, and prenatal diagnosis. The presence of mental retardation and relative infrequency of skeletal fractures distinguish the clinical course of the patients with the Arabic mutation from those of the American and Belgian patients with the His 107-->Tyr mutation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acidosis, Renal Tubular / complications
  • Acidosis, Renal Tubular / enzymology
  • Acidosis, Renal Tubular / genetics
  • Base Sequence
  • Carbonic Anhydrases / deficiency
  • Carbonic Anhydrases / genetics*
  • DNA / genetics
  • DNA Mutational Analysis
  • Female
  • Humans
  • Introns
  • Male
  • Middle East
  • Molecular Sequence Data
  • Osteopetrosis / complications
  • Osteopetrosis / enzymology*
  • Osteopetrosis / genetics*
  • Pedigree
  • Phenotype
  • RNA Splicing / genetics


  • DNA
  • Carbonic Anhydrases