First female with Allan-Herndon-Dudley syndrome and partial deletion of X-inactivation center

Quesada‐Espinosa, Juan Francisco; Garzón-Lorenzo, Lucía; Rosales, Jose Miguel Lezana; Gómez-Rodriguez, Maria José; Sánchez-Calvín, María Teresa; Milla, Carmen Palma; Gómez-Manjón, Irene; Mayoral, Irene Hidalgo; Fuente, Rubén Pérez de la; Arteche‐López, Ana; Álvarez-Mora, María Isabel; Camacho-Salas, Ana; Cruz-Rojo, Jaime; Rodríguez, Irene Lázaro; Morales-Conejo, Montserrat; Núñez-Enamorado, N; Bustamante-Aragonés, Ana; Heras, Rogelio Simón de las; Gomez-Cano, María A.; Ramos-Gómez, Patricia; Sierra-Tomillo, Ollalla; Juárez-Rufián, Alexandra; Gallego-Merlo, J.; Rausell-Sánchez, Laura; Moreno-Garcı́a, Marta; Pozo, Jaime Sánchez del

doi:10.1007/s10048-021-00660-7

Cited by 8 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some researchers believe that a thyroid hormone level with a free T3/T4 ratio above 0.75 is helpful in diagnosing patients. However, in this study, only 67% (6/9) of patients fulfilled this condition ( 24 ). It can be seen that the method has limited diagnostic value in detecting AHDS.…”

Section: Discussioncontrasting

confidence: 68%

See 1 more Smart Citation

Characteristics of Allan-Herndon-Dudley Syndrome in Chinese children: Identification of two novel pathogenic variants of the SLC16A2 gene

et al. 2022

View full text Add to dashboard Cite

ObjectiveThe aim of this study was to identify causative variants associated with Allan-Herndon-Dudley syndrome (AHDS) in two unrelated Chinese families, and to determine their potential pathogenicity. We also summarized the core clinical symptoms of AHDS by reviewing the related literature.MethodsGenomic DNA was isolated from the peripheral blood of AHDS patients and their family members. Whole exome sequencing (WES) was performed on the proband from each family to identify the candidate variants. Subsequently, Sanger sequencing was used to verify the identified candidate variants and to assess co-segregation among the available family members. In silico prediction combined with 3D protein modeling was conducted to predict the functional effects of the variants on the encoded protein.ResultsTwo novel hemizygous variants of SLC16A2, c.1111_1112insGTCTTGT (Gly375fs*6) and c.942delA (Val315fs*28), were detected in two patients. We compared the clinical symptoms of the patients with all patients with AHDS reported in China and those reported in the literature. While both our patients presented symptoms mostly consistent with AHDS, Patient 1 had no abnormal brain structure and thyroid function, and yet showed other symptoms including lactic aciduria, conjunctival hyperemia, vomiting, laryngeal stridor, low immunoglobulin and iron levels.ConclusionsThis study expands the mutation spectrum of AHDS and has clinical value for variant-based prenatal and postnatal screening for this condition. Doctors often have difficulty identifying AHDS by using clinical symptoms. WES can help to identify specific disorder when diagnosis cannot be made based on symptoms alone.

show abstract

Section: Discussioncontrasting

confidence: 68%

“…Currently, only one case of a female patient has been reported, the rest being males. Most heterozygous women have no neurological symptoms, but thyroid function tests may be mildly abnormal, possibly due to altered X chromosome inactivation ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Allan-Herndon-Dudley Syndrome in Chinese children: Identification of two novel pathogenic variants of the SLC16A2 gene

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Due to a preferential inactivation of the normal chromosome, as expected for these cases, there was no functional copy of the SLC16A2 gene, resulting in the expression of the phenotype [5]. Another symptomatic female reported by Quesada-Espinosa et al (2021) [10] presented a de novo 543 kb deletion of the X chromosome including exon 1 of the SLC16A2 gene as well as the JPX and FTX genes. The deleted X chromosome was found to be the active one in 95% of the blood cells, which was attributed to the participation of the JPX and FTX genes in the X-chromosome inactivation.…”

Section: Discussionmentioning

confidence: 86%

“…Regarding the symptomatic carriers, the literature shows two female patients with AHDS who presented markedly skewed X-chromosome inactivation towards the allele without the variant: one due to a balanced X-9 translocation [5], and the other due to a deletion involving the SLC16A2 gene as well as the X-inactivation center [10]. Thus, investigating X-chromosome inactivation in symptomatic carriers of AHDS may also assist the genotype-phenotype correlation.…”

Section: Introductionmentioning

confidence: 99%

Real-Time Observation of “Soft” Magic-Size Clusters during Hydrolysis of the Model Metallodrug Bismuth Disalicylate

Szczerba

Tan

et al. 2021

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Allan-Herndon-Dudley syndrome (AHDS) is characterized by neuropsychomotor developmental delay/intellectual disability, neurological impairment with a movement disorder, and an abnormal thyroid hormone profile. This disease is an X-linked disorder that mainly affects men. We described a female patient with a de novo variant in the SLC16A2 gene, a milder AHDS phenotype, and a skewed X chromosome inactivation profile. We discuss the mechanisms associated with the expression of the phenotypic characteristics in female patients, including SLC16A2 gene variants and cytogenomic alterations, as well as preferential inactivation of the normal X chromosome.

show abstract

“…The MCT8 de ciency can lead to severe psychomotor de cits that include hypotonia, muscle hypoplasia, spastic paraplegia, intellectual disability, movement disorders, and microcephaly often with abnormal thyroid function test (TFT) results such as high free T3, low free T4, and normal or slightly elevated TSH concentrations [2,3]. While the vast majority of AHDS patients are male, a few cases have been reported in females due to defects in X-inactivation processes [4,5]. Causative variants of AHDS have typically been identi ed in protein-coding regions or adjacent junctions.…”

Section: Introductionmentioning

confidence: 99%

Identification of a novel non-coding deletion in Allan-Herndon-Dudley syndrome by long-read HiFi genome sequencing

Yoon,

Lee,

Park

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked disorder caused by a pathogenic variant in the SLC16A2gene. Although most reported variants are found in protein-coding regions or adjacent junctions, structural variations (SVs) within non-coding regions have not been previously reported. Methods: To investigate two male siblings with severe neurodevelopmental disorders and spasticity, who had remained undiagnosed for over a decade and were negative from exome sequencing, we utilized long-read HiFi genome sequencing. We analyzed short-tandem repeats (STRs) and SVs to identify the genetic cause in this familial case. Results: While coding variants and STR analyses yielded negative results, SV analysis revealed a novel hemizygous deletion in intron 1 of the SLC16A2 gene (ChrX:74,460,691-74,463,566; 2,876 bp), inherited from their carrier mother and shared by the siblings. Determination of the breakpoints indicates that the deletion probably resulted from Alu/Alu-mediated rearrangements between homologous AluY pairs. The deleted region is predicted to include multiple transcription factor binding sites, such as Stat2, Zic1, Zic2, and FOXD3, which are crucial for the neurodevelopmental process, as well as a regulatory element including an eQTL (rs1263181) that is implicated in the tissue-specific regulation of SLC16A2 expression, notably in skeletal muscle and thyroid tissues. Conclusions: This report, to our knowledge, is the first to describe a non-coding deletion associated with AHDS, demonstrating the potential utility of long-read sequencing for undiagnosed patients. It may expand the genomic spectrum of AHDS and highlight the identified region with a high priority for future investigation and functional studies.

show abstract

First female with Allan-Herndon-Dudley syndrome and partial deletion of X-inactivation center

Cited by 8 publications

References 23 publications

Characteristics of Allan-Herndon-Dudley Syndrome in Chinese children: Identification of two novel pathogenic variants of the SLC16A2 gene

Characteristics of Allan-Herndon-Dudley Syndrome in Chinese children: Identification of two novel pathogenic variants of the SLC16A2 gene

Real-Time Observation of “Soft” Magic-Size Clusters during Hydrolysis of the Model Metallodrug Bismuth Disalicylate

Identification of a novel non-coding deletion in Allan-Herndon-Dudley syndrome by long-read HiFi genome sequencing

Contact Info

Product

Resources

About