Aarskog Syndrome: Deep Phenotyping and Genomic Landscape of a New Cohort Including Adult Patients.

IF 2.9 3区 医学 Q2 GENETICS & HEREDITY
Gozde Tutku Turgut, Umut Altunoglu, Şahin Avcı, Tuğba Kalaycı, Ayça Dilruba Aslanger, Volkan Karaman, Zehra Oya Uyguner, Hülya Kayserili
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引用次数: 0

Abstract

Aarskog-Scott syndrome (AAS, MIM#305400) is an X-linked disorder characterized by recognizable facial features, short stature, and genitourinary and skeletal malformations. AAS is attributed to pathogenic variants in FGD1, and ~60 patients with a genetic diagnosis have been reported to date. We hereby present a molecularly confirmed cohort of 14 male AAS patients from 13 families. Among 14 patients, 12 were referred during childhood, while two were referred at adulthood due to infertility. Six out of 11 patients with available records had antenatal manifestations, comprising shortened tubular bones, growth restriction, polyhydramnios, pes equinovarus, increased nuchal translucency, fetal hypokinesia, echogenic intracardiac focus, and ambiguous genitalia. In addition to well-described AAS findings, distinctive features observed in multiple patients included variable skin findings (n = 5), renal malformations (n = 2), muscular build (n = 2), and infertility (n = 2). Cardiac (n = 4) and ocular manifestations (n = 6) were identified at significantly higher rates than previously reported. This cohort also presents new patients with osteochondritis dissecans and oligo/azoospermia, providing further evidence to acknowledge these once-reported findings as part of the disease spectrum. Eleven different FGD1 variants, including seven novel ones, were identified through targeted FGD1 sequencing. Two variants were found to be recurrent, detected in two independent families. Our study provides additional insights into the clinical and genotypic landscape of AAS through the largest molecularly confirmed cohort, including two adult patients.

Aarskog综合征:包括成人患者在内的新队列的深层表型和基因组景观。
Aarskog-Scott综合征(AAS, MIM#305400)是一种x连锁疾病,其特征是可识别的面部特征、身材矮小、泌尿生殖系统和骨骼畸形。AAS归因于FGD1的致病变异,迄今为止约有60例患者被报道为遗传诊断。我们在此提出来自13个家庭的14名男性AAS患者的分子确认队列。在14例患者中,12例在儿童期转诊,2例因不孕症在成年期转诊。有记录的11例患者中有6例有产前表现,包括管状骨缩短、生长受限、羊水过多、马蹄内翻、颈部透明度增加、胎儿运动障碍、心内灶回声和生殖器模糊。除了描述良好的AAS表现外,在多个患者中观察到的独特特征包括不同的皮肤表现(n = 5),肾脏畸形(n = 2),肌肉发达(n = 2)和不孕症(n = 2)。心脏(n = 4)和眼部表现(n = 6)的发生率明显高于先前报道。该队列研究还提出了夹层性骨软骨炎和少精/无精子症的新患者,为承认这些曾经报道的发现是疾病谱系的一部分提供了进一步的证据。通过靶向FGD1测序鉴定出11种不同的FGD1变体,其中包括7种新的FGD1变体。在两个独立的家族中发现了两个反复出现的变体。我们的研究通过最大的分子确认队列,包括两名成年患者,为AAS的临床和基因型景观提供了额外的见解。
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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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