RESUMO
OBJECTIVE@#To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome.@*METHODS@#An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS).@*RESULTS@#The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother.@*CONCLUSION@#The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.
Assuntos
Humanos , Lactente , Masculino , Talassemia alfa/diagnóstico , Proteínas Mutadas de Ataxia Telangiectasia/genética , População do Leste Asiático , Deficiência Intelectual/genética , Deficiência Intelectual Ligada ao Cromossomo X/diagnóstico , Linhagem , Proteína Nuclear Ligada ao X/genéticaRESUMO
<p><b>OBJECTIVE</b>To identify potential mutation in a Chinese family featuring X-linked alpha thalassemia/mental retardation syndrome (ATR-X).</p><p><b>METHODS</b>Based on clinical symptoms and inheritance pattern, linkage analysis of X chromosome short tandem repeats (X-STR) loci was carried out to locate the candidate gene. Subsequently, sequences of exons and exon-intron boundaries of the candidate gene were amplified with polymerase chain reaction (PCR). Potential mutations were detected by direct DNA sequencing. All patients were also analyzed for the trait of thalassemia.</p><p><b>RESULTS</b>Linkage analysis indicated the candidate gene to be ATRX. Subsequently, a homozygous missense mutation c.736C>T (p.R246C) was found in exon 9 of ATRX in all of the 3 patients. And a heterozygous mutation c.736C>T (p.R246C) was also identified in the patient's mother and grandmother. Similar mutations were not detected in other members of the family. Alpha thalassemia was detected in the proband and another patient, whose genotypes were determined as -α(3.7)/αα and --(sea)/αα, respectively.</p><p><b>CONCLUSION</b>Missense mutation of c.736C>T in ATRX gene is a mutation hotspot, and p.R246C may disturb the function of ATRX-DNMT3-DNMT3L domain (ADD), which may be responsible for the disease in this family.</p>
Assuntos
Pré-Escolar , Feminino , Humanos , Masculino , Povo Asiático , Genética , DNA Helicases , Genética , Análise Mutacional de DNA , Métodos , Deficiência Intelectual Ligada ao Cromossomo X , Genética , Mutação de Sentido Incorreto , Proteínas Nucleares , Genética , Linhagem , Proteína Nuclear Ligada ao X , Talassemia alfa , GenéticaRESUMO
<p><b>OBJECTIVE</b>To determine the linkage between Smith-Fineman-Myers syndrome (SFMS) and X-linked nuclear protein(XNP) locus.</p><p><b>METHODS</b>Polymerase chain reaction and denaturing polyacrylamide gel electrophoresis were used to genotype two polymorphic short tandem repeats within XNP gene.</p><p><b>RESULTS</b>One of the two short tandem repeats was informative in SFMS family from Shandong, China. Recombination between SFMS locus and XNP gene was observed in the SFMS family.</p><p><b>CONCLUSION</b>XNP gene is not associated with the disease in the SFMS family from Shandong, China. SFMS exhibits locus heterogeneity at molecular level.</p>