Homozygous Sequence Variants in the NPR2 Gene Underlying Acromesomelic Dysplasia Maroteaux Type (AMDM) in Consanguineous Families
Homozygous Sequence Variants in the NPR2 Gene Underlying Acromesomelic Dysplasia Maroteaux Type (AMDM) in Consanguineous Families
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DOI：
10.1111/ahg.12116
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发表时间：
2015-07-01
影响因子：
1.9
通讯作者：
Ahmad, Wasim
中科院分区：
文献类型：
--
作者：
Irfanullah;Umair, Muhammad;Ahmad, Wasim
肢端中肢发育不良是一种常染色体隐性遗传性骨骼疾病，以不成比例的身材矮小伴肢端中肢节缩短为特征。AMDM由位于染色体9 p21-p12上的NPR 2基因突变引起。该基因编码利钠肽受体B（NPR-B），其作为C型利钠肽（CNP）的内源性受体。CNP和NPR-B都被认为是重要的纵向生长调节因子。本研究调查了三个AMDM家系（A、B、C），它们均为常染色体隐性遗传。在家系中建立了与染色体9 p12 -21上的NPR 2基因的连锁。该基因的序列分析发现两个新的错义变异（p.Arg601Ser; p.Arg749Trp）在两个家庭和一个先前报道的剪接位点变异（c.2986+ 2 T>G）在第三个家庭。
Acromesomelic dysplasia Maroteaux type (AMDM) is an autosomal recessive skeletal disorder characterized by disproportionate short stature with shortening of the acromesomelic sections of the limbs. AMDM is caused by mutations in the NPR2 gene located on chromosome 9p21-p12. The gene encodes the natriuretic peptide receptor B (NPR-B) that acts as an endogenous receptor for C-type natriuretic peptide (CNP). Both CNP and NPR-B are considered as important regulators of longitudinal growth. The study presented here investigated three consanguineous families (A, B, C) segregating AMDM in an autosomal recessive manner. Linkage in the families was established to the NPR2 gene on chromosome 9p12-21. Sequence analysis of the gene revealed two novel missense variants (p.Arg601Ser; p.Arg749Trp) in two families and a previously reported splice site variant (c.2986+2T>G) in the third family.