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.

中文翻译：

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具有 PPP1CB 基因变异的生长期毛发松散的 Noonan 综合征：报告的首例家族性病例

Rasopathies 是一组表型重叠的病症，包括 Noonan、具有多个雀斑的 Noonan、具有松散的生长期毛发的 Noonan、Costello、心面皮肤病和神经纤维瘤病 - Noonan 综合征。生长期毛发松散的努南综合征 (NS-LAH) 的临床特征是前额突出、大头畸形、生长激素缺乏、生长期毛发稀疏、松散和生长缓慢、色素沉着过度的皮肤伴湿疹或鱼鳞病、轻度精神运动延迟、鼻音亢进和注意力不集中缺陷多动障碍。SHOC2中的变体导致了大多数情况。格里普等人。鉴定了四个与 NS-LAH 表型相似且具有PPP1CB致病变异的无关个体. 在这项研究中，我们介绍了一个家庭和一名患有 NS-LAH 和PPP1CB变异的患者。第一位患者属于一个可能具有致病性变异 c.545T>A (p.Met182Lys) 的家族，这是迄今为止发表的第一个具有该基因变异的家族。第二名患者港口一个从头致病变种，c.146C> G（p.Pro49Arg）。本研究介绍了另外两名患有这种罕见综合征的患者，以增加该综合征的临床特征，并提供更多证据证明 PPP1CB 中 c.545T>A（p.Met182Lys）变异的致病性，PPP1CB是最近与 NS- 相关的基因拉哈。