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Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurodegenerative disorders characterized by progressive weakness and spasticity in the lower limbs due to pyramidal tract dysfunction. REEP2 mutations have been identified as a cause of "pure" HSP, SPG72, with both autosomal dominant and autosomal recessive inheritance. We describe a rare Nepalese family with early-onset pure-type HSP harboring a heterozygous REEP2 missense mutation (c.119T>G, p.Met40Arg). This is only the second SPG72 family with autosomal dominant inheritance. The proband presented slow and spastic gait at age 2 years and the symptoms progressed slowly. The proband's father and uncle presented even milder symptoms of pure spastic paraplegia. Our study may provide an opportunity to further study the genotype-phenotype correlation of SPG72.

The placenta is an important functional unit for gas transfer between mother and fetus. The placental membrane, consisting of trophoblast layer interposed between maternal and fetal blood, plays an active role for intensity of respiration, but no morphological evidence has been documented. Until now, it has been reported that fetal growth retardation and increased fetal mortality rate usually could be seen at high altitude. In an attempt to find the cause of high perinatal mortality rate in Nepal, this study was undertaken to examine pathologically about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the results were compared with those of 5500 Japanese placentas at Saitama Medical School since 1990. In this study, characteristics of ultrastructural features of the Nepalese placental villi investigated in recent years are reported. (1) The gross characteristics of placental pathology in the Himalayan group were represented by marked subchorionic fibrin deposits and increased chorionic cysts in contrast to low incidence of intervillous thrombosis compared with those of the Japanese group. (2) As characteristics of histological findings of the placental villi between Himalayan and Japanese groups, the incidence of chorangiosis and chorangioma in the Himalayan group was significantly higher than that in the Japanese group. (3) Accompanying an increase of vasculosyncytial membrane (VSM) in the villi, thickness and separation of basement membrane of the syncytium in addition to increased apoptosis of syncytial cell nuclei were recognized. (4) As characteristic ultrastructural features of chorionic villi of Nepalese placentas, an increase of mitochondria and cystic formation of rough endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar to alveolar epithelial type II cell in organellae of the syncytium, were observed. These ultrastructural changes of the placental villous capillaries may be ascribed to hypervascularization caused by the chronic hypoxic state. It is, therefore, presumed that trophoblast cells may play an important role for gas transfer mechanism under such a hypoxic state at high altitude.

It has been reported that both chorangiosis and chorangioma are increased in placentas at high altitudes. In this study, 1.14% of 2448 Japanese placentas obtained at 30-300 m had chorangiosis or chorangioma, compared with 3.24% of the Nepalese placentas (1300-3000 m) and 9.09% of the Tibetan samples (3800-4200 m). The incidence of both pathologies was significantly higher in the Himalayan groups than those of the Japanese group (P < 0.05). Obstetric complications of the 28 Japanese placentas with chorangiosis and chorangioma included Caesarean section 16 (57.1%), abruptio placentae 2 (7.14%), intrauterine growth retardation 3 (10.7%), intrauterine fetal death 4 (14.2%) and placenta praevia 4 (14.2%). Four infants (14.2%) had Apgar scores ranging from 0 to 3. Among 48 Himalayan placentas with chorangiosis and chorangioma, incidence of marked subchorionic fibrin was significantly higher (25%) than in the Japanese group (3.57%) (P < 0.05). The incidence of abnormal insertion of the cord was significantly higher (14.2%) in the Japanese group than in the Himalayan group (5%) (P < 0.05). There was no significant difference in the frequencies of intervillous thrombosis and infarction between the two groups. These findings suggest that the incidence of pathological change such as chorangiosis and chorangioma may be increased in placentas at Himalayan altitudes.