Allelic Variants in Established Hypopituitarism Genes Expand Our Knowledge of the Phenotypic Spectrum.
Allelic Variants in Established Hypopituitarism Genes Expand Our Knowledge of the Phenotypic Spectrum.
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DOI：
10.3390/genes12081128
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发表时间：
2021-07-25
期刊：
影响因子：
3.5
通讯作者：
Carvalho LR
中科院分区：
文献类型：
--
作者：
Nakaguma M;Ferreira NGBP;Benedetti AFF;Madi MC;Silva JM;Li JZ;Ma Q;Bilge Ozel A;Fang Q;Narcizo AM;Cardoso LC;Montenegro LR;Funari MFA;Nishi MY;Arnhold IJP;Jorge AAL;Mendonca BB;Camper SA;Carvalho LR
我们报告四个等位基因变异（三个新的）在三个基因先前建立的原因垂体功能减退症或相关疾病。在一名患有严重的孤立性生长激素缺乏症（IGHD）的男性患者中发现了一种新的生长激素基因纯合变异体，GH 1 c.171delT（p.Phe57Leufs *43）。一个半合子SOX 3等位基因变异（p.Met304Ile）被发现在男性患者IGHD和垂体前叶发育不良。评估蛋白质稳定性的工具YASARA表明，p.Met304Ile使SOX 3蛋白不稳定（ΔΔG = 2.49 kcal/mol）。TALE同源异型盒蛋白基因TGIF 1（c.268C>T：p.Arg90Cys）的一种罕见的杂合错义变体在一名合并垂体激素缺乏症（CPHD）、尿崩症和前脑无裂综合征（HPE）的患者中被发现。这种变异以前曾在一例严重前脑无裂畸形患者中报道过，并显示会影响TGIF 1功能。在一例CPHD、垂体发育不全和异位后叶患者中发现了一种新的杂合子TGF-1变异体（c.82T>C：p.Ser28Pro）。这两种TGIF 1变体都具有不完全显性遗传的常染色体显性遗传模式。总之，我们在垂体功能减退症患者的三个基因中发现了等位基因变异。我们讨论了这些变异和相关的患者表型与以前报道的这些基因的变异，扩大我们的知识，在患者人群的表型谱。
We report four allelic variants (three novel) in three genes previously established as causal for hypopituitarism or related disorders. A novel homozygous variant in the growth hormone gene, GH1 c.171delT (p.Phe 57Leufs*43), was found in a male patient with severe isolated growth hormone deficiency (IGHD) born to consanguineous parents. A hemizygous SOX3 allelic variant (p.Met304Ile) was found in a male patient with IGHD and hypoplastic anterior pituitary. YASARA, a tool to evaluate protein stability, suggests that p.Met304Ile destabilizes the SOX3 protein (ΔΔG = 2.49 kcal/mol). A rare, heterozygous missense variant in the TALE homeobox protein gene, TGIF1 (c.268C>T:p.Arg90Cys) was found in a patient with combined pituitary hormone deficiency (CPHD), diabetes insipidus, and syndromic features of holoprosencephaly (HPE). This variant was previously reported in a patient with severe holoprosencephaly and shown to affect TGIF1 function. A novel heterozygous TGIF1 variant (c.82T>C:p.Ser28Pro) was identified in a patient with CPHD, pituitary aplasia and ectopic posterior lobe. Both TGIF1 variants have an autosomal dominant pattern of inheritance with incomplete penetrance. In conclusion, we have found allelic variants in three genes in hypopituitarism patients. We discuss these variants and associated patient phenotypes in relation to previously reported variants in these genes, expanding our knowledge of the phenotypic spectrum in patient populations.
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DOI：
10.1083/jcb.75.2.464
发表时间：
1977-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Takeichi M
通讯作者：
Takeichi M
影响因子：
9.8
作者：
Tata B;Huijbregts L;Jacquier S;Csaba Z;Genin E;Meyer V;Leka S;Dupont J;Charles P;Chevenne D;Carel JC;Léger J;de Roux N
通讯作者：
de Roux N
影响因子：
3.8
作者：
El-Jaick, Kenia B.;Powers, Shannon E.;Muenke, Maximilian
通讯作者：
Muenke, Maximilian
影响因子：
9.8
作者：
Smith, Joshua D.;Hing, Anne V.;Cunningham, Michael L.
通讯作者：
Cunningham, Michael L.
影响因子：
16.6
作者：
Tommiska J;Känsäkoski J;Skibsbye L;Vaaralahti K;Liu X;Lodge EJ;Tang C;Yuan L;Fagerholm R;Kanters JK;Lahermo P;Kaunisto M;Keski-Filppula R;Vuoristo S;Pulli K;Ebeling T;Valanne L;Sankila EM;Kivirikko S;Lääperi M;Casoni F;Giacobini P;Phan-Hug F;Buki T;Tena-Sempere M;Pitteloud N;Veijola R;Lipsanen-Nyman M;Kaunisto K;Mollard P;Andoniadou CL;Hirsch JA;Varjosalo M;Jespersen T;Raivio T
通讯作者：
Raivio T