Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations.
Clinical and Biochemical Phenotypes in a Family With ENPP1 Mutations.
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DOI：
10.1002/jbmr.3938
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发表时间：
2020-04
期刊：
影响因子：
--
通讯作者：
Wermers RA
中科院分区：
文献类型：
--
作者：
Kotwal A;Ferrer A;Kumar R;Singh RJ;Murthy V;Schultz-Rogers L;Zimmermann M;Lanpher B;Zimmerman K;Stabach PR;Klee E;Braddock DT;Wermers RA
ENPP 1基因的失活突变与婴儿全身性动脉钙化（GACI）和常染色体隐性低磷血症佝偻病2型（ARHR 2）相关。我们的目的是调查一个具有ENPP 1单等位基因和双等位基因突变的家族的表型谱，在通过全外显子组测序鉴定一名54岁女性后，ENPP 1的双等位基因突变，c.323G > T; p.Cys108Phe和c.1441C > T; p.Arg481Trp。包括先证者在内，2例受试者有ENPP 1的双等位基因突变，5例有单等位基因突变，2例无突变。在3例单等位基因突变受试者中发现了与GACI相关的已知致病性变异的母体突变，而在2例单等位基因突变受试者中发现了既往未报告的父亲突变。2例双等位基因突变受试者均出现双侧股骨弯曲、关节周围矿物质沉积、正常血钙的原发性甲状旁腺功能亢进伴多腺体甲状旁腺切除术、颈动脉内膜中层厚度增加，1例受试者还观察到附着点病变。在两个具有双等位基因突变的受试者中，完整的FGF 23升高，而C-末端FGF 23仅在一个受试者中升高，PPi在一个受试者中降低。单等位基因突变的受试者没有关节周围钙化或骨畸形。总之，具有引起突变的双等位基因GACI的患者可以很好地存活到成年期，并且尽管具有相同的双等位基因ENPP 1致病变体，但临床和生化表现可以显著不同，并且包括之前未描述的附着点病和原发性甲状旁腺功能亢进。虽然单等位基因ENPP 1变异的携带者似乎不受经典疾病表现的影响，但可能有微妙的生化和临床发现值得进一步研究。© 2019美国骨与矿物质研究学会。
Inactivating mutations of the ENPP1 gene are associated with generalized arterial calcification of infancy (GACI) and less often autosomal-recessive hypophosphatemic rickets type 2 (ARHR2). We aimed to investigate the spectrum of phenotypes in a family with monoallelic and biallelic mutations of ENPP1 after identification through whole exome sequencing of a 54-year-old female with biallelic mutation of ENPP1, c.323G > T; p.Cys108Phe and c.1441C > T; p.Arg481Trp. Including the proband, 2 subjects had biallelic mutations, 5 had monoallelic mutations, and 2 had no mutation of ENPP1. The maternal mutation, a known pathogenic variant associated with GACI, was found in 3 subjects with monoallelic mutations, while the paternal mutation, which was not previously reported, was present in 2 subjects with monoallelic mutations. Both subjects with biallelic mutations had bowing of bilateral femurs, periarticular mineral deposition, normocalcemic primary hyperparathyroidism with multigland parathyroidectomy, increased carotid intima-media thickness, and enthesopathy was also noted in one subject. Intact FGF23 was elevated in both subjects with biallelic mutations, while C-terminal FGF23 was only elevated in one and PPi was reduced in one. Subjects with monoallelic mutations did not have periarticular calcifications or bone deformities. To conclude, patients with biallelic GACI causing mutations can survive well into adulthood, and despite the same biallelic ENPP1 pathogenic variants, clinical and biochemical manifestations can significantly differ, and include enthesopathy and primary hyperparathyroidism, which have not been previously described. Although carriers of monoallelic ENPP1 variants appear unaffected by classic disease manifestations, there may be subtle biochemical and clinical findings that warrant further investigation. © 2019 American Society for Bone and Mineral Research.
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DOI：
10.1073/pnas.1319582110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Jansen, Robert S.;Kucukosmanoglu, Asli;van de Wetering, Koen
通讯作者：
van de Wetering, Koen
影响因子：
11.1
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Dedinszki D;Szeri F;Kozák E;Pomozi V;Tőkési N;Mezei TR;Merczel K;Letavernier E;Tang E;Le Saux O;Arányi T;van de Wetering K;Váradi A
通讯作者：
Váradi A
影响因子：
9.8
作者：
Lorenz-Depiereux, Bettina;Schnabel, Dirk;Strom, Tim M.
通讯作者：
Strom, Tim M.
DOI：
10.1161/atvbaha.114.304017
发表时间：
2014-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Jansen RS;Duijst S;Mahakena S;Sommer D;Szeri F;Váradi A;Plomp A;Bergen AA;Oude Elferink RP;Borst P;van de Wetering K
通讯作者：
van de Wetering K
影响因子：
5.7
作者：
Jansen, Silvia;Perrakis, Anastassis;Bollen, Mathieu
通讯作者：
Bollen, Mathieu