The first two non-Finnish HYLS1 variants: Expanding the phenotypic spectrum of hydrolethalus syndrome,Clinical Genetics

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The first two non-Finnish HYLS1 variants: Expanding the phenotypic spectrum of hydrolethalus syndrome
Clinical Genetics ( IF 2.9 ) Pub Date : 2021-07-01 , DOI: 10.1111/cge.14021
Leïla Ghesh _{1,

2} , Marie Denis Musquer _{2,

3} , Louise Devisme ₄ , Morgane Stichelbout ₄ , Lucile Boutaud _{5,

6} , Nadia Elkhartoufi ₅ , Pascal Vaast ₇ , Odile Boute ₈ , Anne-Sophie Riteau _{9,

10} , Claudine Le Vaillant ₉ , Norbert Winer _{9,

11} , Madeleine Joubert _{2,

3} , Stéphane Bezieau _{1,

12} , Sophie Thomas ₆ , Tania Attie-Bitach _{5,

6} , Claire Beneteau _{1,

2}

Affiliation

Service de Génétique Médicale, CHU Nantes, Nantes, France.
UF de Fœtopathologie et Génétique, CHU de Nantes, Nantes, France.
Service d'Anatomie et Cytologie Pathologiques, CHU Nantes, Nantes, France.
Service d'Anatomie et Cytologie Pathologiques, CHRU de Lille, Lille, France.
Service d'Histo-Embryologie et de Cytogénétique, Unité d'Embryofoetopathologie, Hôpital Necker Enfants-Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
Institut Imagine, INSERM U1163, Université Paris Descartes, Sorbonne Paris Cite, Paris, France.
Service d'Echographie Fœtale et de Médecine Fœtale, CHRU de Lille, Lille, France.
Service de Génétique Médicale, CHRU de Lille, Lille, France.
Service de Gynécologie-Obstétrique, CHU Nantes, Nantes, France.
Service de Gynécologie-Obstétrique, Clinique Jules Vernes, Nantes, France.
UMR PhAN 1280 NUN INRAE F-44000, Université de Nantes, Nantes, France.
L'institut du Thorax, INSERM, CNRS, UNIV Nantes, CHU de Nantes, Nantes, France.

Hydrolethalus syndrome (HLS) is a rare lethal fetal malformation disorder related to ciliogenesis disruption. This condition is more frequent in Finland where a founder missense variant in the HYLS1 gene was identified. No other HYLS1 variant has hitherto been implicated in HLS. We report two unrelated French fetuses presenting with a phenotype of HLS with brain abnormalities, limbs malformations with pre and postaxial hexadactyly and abnormal genitalia. These two fetuses have compound heterozygous variants in HYLS1. The first allele carries the same Finnish missense variant (NM_145014.2: c.632A > G, p.[Asp211Gly]) in both fetuses and the second allele carries a new missense variant (c.662G > C, p.[Arg221Pro]) in the first fetus, and a new nonsense variant (c.613C > T, p.[Arg205*]) in the second fetus. This is the first report of HYLS1 mutated cases outside Finland. Both cases presented here are consistent with HLS with additional malformations, allowing expansion of the phenotypic presentation previously described.

中文翻译：

前两个非芬兰 HYLS1 变体：扩大嗜水综合征的表型谱

Hydrolethalus 综合征 (HLS) 是一种罕见的致死性胎儿畸形疾病，与纤毛发生中断有关。这种情况在芬兰更为常见，其中发现了HYLS1基因中的创始人错义变体。迄今为止，没有其他HYLS1变体与 HLS 有关。我们报告了两个无关的法国胎儿，其表现出 HLS 表型，伴有脑部异常、四肢畸形、轴前和轴后六指畸形和异常生殖器。这两个胎儿在HYLS中具有复合杂合变体1. 第一个等位基因在两个胎儿中携带相同的芬兰错义变体 (NM_145014.2: c.632A > G, p.[Asp211Gly])，第二个等位基因携带一个新的错义变体 (c.662G > C, p.[第一个胎儿中的 Arg221Pro]），以及第二个胎儿中的一个新的无意义变体 (c.613C > T, p.[Arg205*])。这是芬兰境外首次报告HYLS1突变病例。此处介绍的两种情况都与具有额外畸形的 HLS 一致，允许扩展先前描述的表型呈现。

更新日期：2021-09-03

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