The severity of HPP clinical manifestations varies greatly. HPP has also been reported in Hispanics, Japanese and Chinese populations, but the prevalence of HPP in China is still unknown ( Whyte, 2017 Mao et al., 2019). The ethnic groups of the patients involved in this study were Han (PA-1, 2, 3 and 5) and Zhuang (PA-4). The prevalence in the white-skinned populations of the United States is higher than those of black origins. Increased PPi levels can causes impaired skeletal mineralization by blocking hydroxyapatite crystal formation, thus predisposing an individual to fractures, fracture healing complications, and bone marrow edema (BME) ( Mao et al., 2019 Orimo, 2010 Weiss et al., 1988b Zhou et al.,and 2012).Īlthough HPP is rare, but it is relatively common among Canadian Mennonites. A loss of function variation within the gene ALPL will reduce the alkaline phosphatase (ALP) activity, which can lead to an accumulation of its substrates including pyridoxal-5-phosphate (PLP) and PPi. Under physiological conditions, it functions as an ecto-phosphatase and it hydrolyzes inorganic pyrophosphate (PPi) to phosphate (Pi) to form hydroxyapatite, and this balance is essential for the bone mineralization. TNSALP is a homodimeric enzyme where each monomer is composed of 524 amino acids (57.2 kDa). ALPL is located on chromosome 1p36.1 and consists of 12 exons distributed over 50 kb, encoding for a tissue non-specific alkaline phosphatase (TNSALP) ( Xu et al., 2018). These variations can have obvious heterogeneity and can be inherited in an autosomal dominant (AD) or recessive (AR) manner ( ). So far, at least 411 ALPL gene variants have been reported. Hypophosphatasia (HPP, OMIM: 146300, 241500, 241510) is primarily caused by ALPL gene variations (OMIM: 171760). Our study extends the pool of ALPL variants in different populations. Odonto HPP (PA-5) only presents as dental abnormality with severe dental caries and decreased ALP activity. Among the variants, c.1247G > T/p.Gly416Val (PA-4) c.1178A > G/p.Asn393Ser (PA-5) and c.707A > G/p.Tyr236Cys (PA-1, PA-2) have never been reported before.Ĭonclusion: Clinical phenotypes of perinatal HPP (PA-1,PA-2,PA-3 and PA-4) include skeletal dysplasia, shorter long bones, bowing of long bones, tetraphocomelia, abnormal posturing and abnormal bone ossification. All cases reported in this study were autosomal recessive. These variations caused two types of HPP: perinatal HPP and Odonto HPP. Results: Eight variants in the ALPL gene in the five unrelated Chinese patients (PA-1: c.649_650insC and c.707A > G PA2: c.98C > T and c.707A > G PA3: c.407G > A and c.650delTinsCTAA PA4: c.1247G > T (homozygous) PA5: c.406C > T and c.1178A > G NM_000478.5) were found. Whole-exome sequencing was performed in order to aid diagnosis of the patients. Methods: We investigated five patients with skeletal dysplasia in the clinic. ALP deficiency is the key to the pathogenesis of abnormal metabolism and skeletal system damage in HPP patients. The clinical presentation is a continuum ranging from a prenatal lethal form with no skeletal mineralization to a mild form with late adult onset presenting with non-pathognomonic symptoms. 2Laboratory of Genetic Metabolism Center, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Chinaīackground: Hypophosphatasia (HPP) is an autosomal genetic disorder characterized biochemically by abnormal of bone parameters and serum alkaline phosphatase (ALP) activity as well as clinically by deficiency of teeth and bone mineralization.1The Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Guangxi Birth Defects Prevention and Control Institute, Nanning, China.Qiang Zhang 1,2*, Zailong Qin 1,2, Shang Yi 2, Hao Wei 2, Xun zhao Zhou 2 and Fei Shen 2
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