Identification of a De Novo Heterozygous Frameshift Variant in FMR1 in a Female With Fragile X Syndrome

IF 2.3 3区医学 Q2 GENETICS & HEREDITY

Clinical Genetics Pub Date : 2025-05-08 DOI:10.1111/cge.14761

Alejandro Parra, Juan A. Jimenez-Estrada, Valeria Vásquez-Amell, Mario Cazalla, Manuel Rodríguez-Canó, Natalia Gallego-Zazo, Lucia Miranda, Mónica Mora-Gómez, Elena Vallespín, Rocío Mena, Luis Fernández, Cristina Silván, Pedro Arias, Marta Dominguez-Jiménez, Encarna Guillén-Navarro, Julián Nevado, Jair Tenorio-Castano, Víctor L. Ruiz-Pérez, Pablo Lapunzina

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引用次数: 0

Abstract

We present a 28-year-old Spanish female with a de novo heterozygous variant in FMR1 (NM_002024.6:c.1061_1062delAA), p.(Lys354Thrfs*15) detected by whole-exome sequencing and confirmed by Sanger sequencing from cDNA. She was born full-term with neonatal jaundice requiring phototherapy. At age 11, she exhibited weight and head circumference > 97th percentile, global developmental delay, mild ID (IQ: 71), and hyperactivity. FMR1 CGG analysis was normal. NGS panel of over 200 OGS-related genes found no pathogenic variants. By age 28, she presented with macrocephaly, coarse facial features, mild joint hypermobility, left talo-valgus, a port-wine stain, a café-au-lait spot, and a piezogenic papule. Herein, we describe a clinical and molecular report of the second FXS female patient due to a heterozygous point variant. This study was approved by the ethical committee of Hospital Universitario La Paz (CEIm PI-446), and informed consent was obtained from the patient and her parents.

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脆性X综合征女性FMR1基因杂合移码变异的鉴定

我们报道了一名28岁的西班牙女性，通过全外显子组测序检测到FMR1 (NM_002024.6:c.1061_1062delAA), p.（Lys354Thrfs*15）的新生杂合变异，并通过cDNA的Sanger测序进行了证实。她足月出生时患有需要光疗的新生儿黄疸。在11岁时，她表现出体重和头围为97百分位，整体发育迟缓，轻度ID （IQ: 71）和多动症。FMR1 CGG分析正常。超过200个ogs相关基因的NGS面板未发现致病性变异。到28岁时，她出现了大头畸形，面部特征粗糙，轻度关节过度活动，左距外翻，葡萄酒斑，咖啡斑和压源性丘疹。在此，我们描述了第二例因杂合点变异引起的FXS女性患者的临床和分子报告。本研究经拉巴斯大学医院伦理委员会（ceem PI-446）批准，并获得患者及其父母的知情同意。

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来源期刊

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