Noonan syndrome with loose anagen hair with variants in the PPP1CB gene: First familial case reported
Noonan syndrome with loose anagen hair with variants in the PPP1CB gene: First familial case reported
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DOI：
10.1002/ajmg.a.62089
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发表时间：
2021-01-25
影响因子：
2
通讯作者：
Gravina, Luis Pablo
中科院分区：
文献类型：
--
作者：
Huckstadt, Victoria;Chinton, Josefina;Gravina, Luis Pablo
皮肤病是一组表型重叠的疾病，包括努南综合征、努南综合征伴多个痣、努南综合征伴生长性毛发疏松、Costello综合征、心脏-面部-皮肤综合征和神经纤维瘤病-努南综合征。Noonan综合征伴毛发疏松（NS-LAH）的临床特征为前额突出、头大、生长激素缺乏、毛发稀疏、疏松、生长缓慢、皮肤色素沉着并伴有湿疹或鱼鳞病、轻度精神运动迟缓、高鼻音和注意缺陷多动障碍。大多数情况下是由SHOC2中的变体引起的。Gripp等人发现了4个与NS-LAH表型相似且PPP1CB致病变异的无亲缘关系个体。在这项研究中，我们报告了一个家庭和一个患有NS-LAH和PPP1CB变异的患者。第一位患者属于一个可能具有致病变异的家族，c.545T >a (p.Met182Lys)，这是迄今为止发表的第一个具有该基因变异的家族。第二例患者携带一种新的致病变异，c.146C >g （p.p or49arg）。本研究提出了另外两例患有这种罕见综合征的患者，以增加该综合征的临床特征，并为PPP1CB中的c.545T>A （p.Met182Lys）变异的致病性提供更多证据，PPP1CB基因最近与NS-LAH相关。
Rasopathies are a group of phenotypically overlapping conditions that include Noonan, Noonan with multiple lentigines, Noonan with loose anagen hair, Costello, Cardio-facio-cutaneous, and Neurofibromatosis-Noonan syndromes. Noonan syndrome with loose anagen hair (NS-LAH) is clinically characterized by prominent forehead, macrocephaly, growth hormone deficiency, sparse, loose and slow-growing anagen hair, hyperpigmented skin with eczema or ichthyosis, mild psychomotor delays, hypernasal voices, and attention deficit hyperactivity disorder. Variants in SHOC2 are responsible for the majority of the cases. Gripp et al. identified four unrelated individuals with similar phenotype to NS-LAH with pathogenic variants in PPP1CB. In this study, we present one family and one patient with NS-LAH and variants in PPP1CB. The first patient belongs to a family with a likely pathogenic variant, c.545T>A (p.Met182Lys), the first family published so far with a variant in this gene. The second patient harbors a de novo pathogenic variant, c.146C>G (p.Pro49Arg). This study presents two additional patients with this rare syndrome in order to increase the clinical characterization of the syndrome and provide more evidence of the pathogenicity of the c.545T>A (p.Met182Lys) variant in PPP1CB, a gene recently associated with NS-LAH.