J Korean Med Sci.  2011 Jan;26(1):146-149. 10.3346/jkms.2011.26.1.146.

The First Case of X-linked Alpha-thalassemia/Mental Retardation (ATR-X) Syndrome in Korea

• Yun KW
• Chae SA
• Lee JJ
• Yun SW
• Yoo BH
• Lim IS
• Choi ES
• Lee MK

• KMID: 1777991
• DOI: http://doi.org/10.3346/jkms.2011.26.1.146

Abstract

Mutation of the ATRX gene leads to X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome and several other X-linked mental retardation syndromes. We report the first case of ATR-X syndrome documented here in Korea. A 32-month-old boy came in with irritability and fever. He showed dysmorphic features, mental retardation and epilepsy, so ATR-X syndrome was considered. Hemoglobin H inclusions in red blood cells supported the diagnosis and genetic studies confirmed it. Mutation analysis for our patient showed a point mutation of thymine to cytosine on the 9th exon in the ATRX gene, indicating that Trp(C), the 220th amino acid, was replaced by Ser(R). Furthermore, we investigated the same mutation in family members, and his mother and two sisters were found to be carriers.

Keyword

Alpha-Thalassemia; Mental Retardation, X-Linked; ATRX; Hemoglobin H

MeSH Terms

Amino Acid Substitution
Body Dysmorphic Disorders/complications
Child, Preschool
DNA Mutational Analysis
Epilepsy/complications
Exons
Hemoglobin H/*genetics
Humans
Male
Mental Retardation/complications
Mental Retardation, X-Linked/complications/diagnosis/genetics
Point Mutation
Republic of Korea
alpha-Thalassemia/complications/diagnosis/genetics

Figure

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  Fig. 1 Facials features of the patient. Our patient expressed the typical facial phenotype comprising epicanthus, midface hypoplasia, flat nasal bridge, small triangular nose with anteverted nostrils, carp-shaped mouth with full lips, and dental diastema at age 6 months (A) and 3 yr (B).

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  Fig. 2 Photomicrograph of the peripheral blood of our case with ATR-X syndrome. It shows cells containing HbH inclusions in our patient (A), and also his mother (B) and eldest sister (C).

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  Fig. 3 Sequences of ATRX gene amplified by primer pair for mutation analysis. Underlined sequences in each box present exon regions of ATRX gene. Blue, pink and yellow color boxes present sequences of primer pairs. Putative mutation site is indicated as red boxes. (A) amplified sequences by ATRX A primer pairs, (B) amplified sequences by ATRX B primer pairs, (C) amplified sequences by ATRX C.

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  Fig. 4 PCR amplification by ATRX primers. M, size marker; 1, patients's father; 2, patients's mother; 3, ATRX patient, 4, patients's sister 1; 5, patients's sister 2.

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  Fig. 5 Sequence of mutation region detected by ATRX B reverse primer. Sequencing conducted under BigDyeTM terminator cycling conditions. The reacted products purified using ethanol precipitation and run using Automatic sequencer 3730xl. (A) ATRX patient's father, (B) ATRX patient's mother, (C) ATRX patient, (D) ATRX patient's sister 1, (E) ATRX patient's sister 2.

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