Aker et al. (2012) studied 4 affected children from 2 consanguineous Palestinian families with osteopetrosis (OPT). All 4 patients had older relatives with OPT, and were suspected of having OPT at 1 to 4 months of age because ... Aker et al. (2012) studied 4 affected children from 2 consanguineous Palestinian families with osteopetrosis (OPT). All 4 patients had older relatives with OPT, and were suspected of having OPT at 1 to 4 months of age because of macrocephaly or failure to thrive due to feeding problems caused by upper airway issues. Examination revealed age-appropriate neurocognitive development, increased head circumference, broad open fontanel, frontal bossing, and hepatosplenomegaly. Hearing was normal, but vision was impaired due to the presence of severe optic nerve atrophy, although the retinas were intact. Laboratory investigation revealed anemia, thrombocytopenia, and high lactate dehydrogenase (LDH). Radiography showed dense bones with no distinction between outer and inner plates due to extensive encroachment of cortical bone into the medullary space. Brain CT disclosed narrowed optic and auditory canals with sclerosis of the semicircular canals; the ethmoid and mastoid air cells and sphenoid sinuses were fully ossified. Two of the patients underwent bone marrow transplantation at ages 10 months and 19 months, respectively, and at follow-up had normal growth and development. One patient died at 32 months of age.
In affected children from 2 unrelated consanguineous Palestinian families segregating autosomal recessive osteopetrosis (OPT) mapping to chromosome 7p15, Aker et al. (2012) sequenced 5 candidate genes and identified homozygosity for a missense mutation in the SNX10 gene (R51Q; ... In affected children from 2 unrelated consanguineous Palestinian families segregating autosomal recessive osteopetrosis (OPT) mapping to chromosome 7p15, Aker et al. (2012) sequenced 5 candidate genes and identified homozygosity for a missense mutation in the SNX10 gene (R51Q; 614780.0001) that segregated with disease in both families. Screening of additional unrelated OPT patients identified another consanguineous Palestinian family in which 2 affected sisters also carried the mutation. Screening of 211 ethnically matched controls revealed 1 carrier of the R51Q mutation.