human
***task***
the task is to summarize an input biomedical literature in six sentences

***input***
the input is a biomedical literature

***output***
the output is the summary of an input biomedical literature in six sentences

***documentation***

***examples***

input: the rare association between - thalassemia and mental retardation was first recognized in 1981 by weatherall and colleagues ( 1 ) . then , in 1995 , in a case of - thalassemia / mental retardation ( atr - x ) syndrome , mutations in the atrx gene locus xq13 .3 were first reported ( 2 ) . since then , studies have identified 127 mutations in this gene in patients with atr - x syndrome ( 3 - 7 ) . while the cellular function of atrx has not yet been fully elucidated , the characteristics of the syndrome suggest that atrx probably functions as part of a chromatin remodeling complex to regulate the transcription of a discrete set of target genes , of which - globin genes involved in brain development are the best characterized example ( 8 - 10 ) . although there have been many studies and case reports of this syndrome and the atrx gene all over the world , no case has been reported in korea until now . a 32 - month - old boy was admitted to our hospital with two days of irritability and fever . he was born with a birth weight of 2.9 kg by normal spontaneous vaginal delivery at 40 weeks gestation to a healthy 28 - yr - old g3p2 mother . his delivery was non - eventful , but there was flexion deformity of both his middle fingers , so he was transferred to our hospital and underwent many diagnostic tests and physical therapies in january , 2002 . he showed mild general hypotonia in that his cry was weak , and he sucked poorly during early infancy . he had epileptic seizures 6 times since the age of 15 months despite taking anti - epileptic medications . a diagnosis of mental retardation complicated by epilepsy was made , and his development was noted to be markedly delayed . he raised his head at age 7 months , sat up at 26 months , and had not yet acquired the ability to stand . he had a flat and mid - hypoplastic face with prognathism , narrow and upward slanting palpebral fissures with hypertelorism , low - set ears , a small crashed nose , widely spaced incisors , carp - like mouth , and round back ( fig .1 ) . he demonstrated repeated stereotyped behavior like hitting his chin with his palm ; this behavior was often associated with emotional outbursts . soon after admission , a generalized tonic - clonic type seizure was started and lasted approximately one hour ; at that time his vital signs were as follows : blood pressure 100/60 mmhg , pulse rate 138 bpm , respiration rate 32 bpm , and body temperature 38.5 . mild throat injection was seen , but other systemic examinations were normal . on neurologic exam , mental status was alert , all cranial nerve exams were normal , and muscle tone in both extremities were decreased to grade iv / iv bilaterally but all deep tendon reflexes were physiologic . initial laboratory investigations revealed : hemoglobin 12.7 g / dl , platelet count 374,000 / l and white blood cell count 11,780 / l . the c - reactive protein was slightly elevated at 19.0 mg / dl on the day of admission and returned to normal 3 days later . a sleep electroencephalogram revealed intermittent high - amplitude slow wave discharges from the temporo - occipital area , representing mild cerebral dysfunction . on radiologic evaluation , spine radiography revealed mild scoliosis . the characteristic facial features and mental retardation of the patient led us to consider atr - x syndrome ; thus , peripheral rbcs were screened for hemoglobin h ( hbh ) inclusion bodies . hbh inclusions were detected under the microscope in 1.1 % of brilliant cresyl blue stained rbcs , consistent with the diagnosis of atr - x syndrome ( fig . the patient 's father , mother and two sisters were all given the same test ; only his mother and eldest sister had the same findings . genomic dna from the peripheral blood of our patient and his 4 family members was extracted with the wizard genomic dna purification kit ( promega , madison , wi , usa ) and used as a template for amplification of the atrx gene . polymerase chain reaction ( pcr ) was separated into three parts and carried out with sequence - specific oligonucleotide primers containing 20 known major mutation sites ( table 1 , figs . 3 , 4 ) . pcr amplification using each primercycling conditions were one cycle at 95 for 5 min , followed by 35 cycles of 95 for 30 sec , at an annealing temperature adjusted to each primer 's ( tm ) for 30 sec , 72 for 30 sec , followed by one cycle at 72 for 7 min . for direct sequencing , the pcr products were purified using a pcr clean - up system offered by promega . dna sequencing was performed using the purified pcr products as template , the same primers as those used for template generation , the bigdye terminator cycle sequencing ready reaction kit ( applied biosystems , foster city , ca , usa ) , and automatic sequencer abi prism 3730 xl dna analyzer ( applied biosystems , foster city , ca , usa ) . sequence data were assembled and compared to that of a previously reported atrx sequence from accession number z84487 using the dnastar software ( dnastar inc . , madison , wi , usa ) . mutation analysis for our patient showed a point mutation on the 9th exon in the atrx gene of thymine to cytosine so that trp ( c ) , the 220th amino acid , was replaced by ser ( r ) ( fig . we investigated the same mutation in his 4 family members , and his mother and two sisters were found to be carriers . the x - linked - thalassemia mental retardation syndrome is a serious recessive disorder resulting from mutations in the atrx gene , mapping in xq13 .3 and coding for a protein containing the signature motif of the snf2 family of atpases . members of this protein family are thought to act generally as part of large multi - protein complexes and impart on those complexes the ability to utilize the energy of atp hydrolysis to remodel the structure of chromatin and thereby regulate protein / dna interactions ( 11 ) . this disease is very rare , probably with an incidence of less than 1/100 ,000 live - born males ( 11 ) . affected males present with severe mental retardation , a typical facial appearance , microcephaly , urogenital anomalies , and an atypical form of - thalassemia . pregnancy is usually uneventful , proceeds to term , and , in 90 % of cases , birth weight is normal . affected neonates usually have marked hypotonia and associated feeding difficulties . in early childhood , all milestones are delayed . as the affected individuals grow older , there is often a tendency toward spasticity . a number of patients have reportedly had jerking movements that are not associated with epileptiform activity on eeg . brain imaging studies frequently show no abnormality , although mild cerebral atrophy or agenesis of the corpus callosum may be seen . the distinctive facial traits are most readily recognized in early childhood : the frontal hair is often upswept ; there is telecanthus , epicanthic folds , midface hypoplasia , and a small , triangular , upturned nose . the upper lip is tented and the lower lip is full and everted , giving the mouth a " carp - like " appearance . the frontal incisors are frequently widely spaced , and the tongue protrudes . genital abnormalities are seen in 80 % of these children . a wide range of relatively mild skeletal abnormalities have been noted . the tendency to aspiration is commonly implicated as a cause of death in early childhood . constipation is common and in some individuals is a major problem to manage . a wide range of cardiac and renal abnormalities also has been noted . there is considerable variation in the hematologic manifestations associated with atrx mutations ( 11 ) . a number of families have been identified in which some or all of the affected members have no signs of - thalassemia ; despite lack of these signs , however , diagnosis of - thalassemia requires only a simple investigation . they are intellectually normal and have no consistent physical manifestations , because they show preferential inactivation of the mutated x - chromosome . rare cells with hbh inclusions may be found in approximately one fourth of obligate carriers ( 12 ) . in our case , there were hbh inclusions in 2 of 3 carriers . but recently , there have been some cases of females with atrx mutations with phenotypical abnormalities . ( 13 ) reported a carrier mother who showed non - skewed x - inactivation with moderate mental retardation . ( 14 ) described a 4 - yr - old girl with typical features of atr - x syndrome , carrying the recurrent r246c mutation of atrx . they showed that her pattern of x - inactivation was totally skewed and that her active x chromosome , which harbors the atrx mutation , was maternally inherited . we report the first korean case of atr - x syndrome in a 32 - month - old boy . now , we can consider atr - x syndrome in a young male child with characteristic facial features and neurologic abnormalities of unknown etiology , and get simple screening test for hbh inclusions so that adequate and early management should be started .
output:

agent
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 .
***task***
the task is to summarize an input biomedical literature in six sentences

***input***
the input is a biomedical literature

***output***
the output is the summary of an input biomedical literature in six sentences

***documentation***

***examples***

input: the rare association between - thalassemia and mental retardation was first recognized in 1981 by weatherall and colleagues ( 1 ) . then , in 1995 , in a case of - thalassemia / mental retardation ( atr - x ) syndrome , mutations in the atrx gene locus xq13 .3 were first reported ( 2 ) . since then , studies have identified 127 mutations in this gene in patients with atr - x syndrome ( 3 - 7 ) . while the cellular function of atrx has not yet been fully elucidated , the characteristics of the syndrome suggest that atrx probably functions as part of a chromatin remodeling complex to regulate the transcription of a discrete set of target genes , of which - globin genes involved in brain development are the best characterized example ( 8 - 10 ) . although there have been many studies and case reports of this syndrome and the atrx gene all over the world , no case has been reported in korea until now . a 32 - month - old boy was admitted to our hospital with two days of irritability and fever . he was born with a birth weight of 2.9 kg by normal spontaneous vaginal delivery at 40 weeks gestation to a healthy 28 - yr - old g3p2 mother . his delivery was non - eventful , but there was flexion deformity of both his middle fingers , so he was transferred to our hospital and underwent many diagnostic tests and physical therapies in january , 2002 . he showed mild general hypotonia in that his cry was weak , and he sucked poorly during early infancy . he had epileptic seizures 6 times since the age of 15 months despite taking anti - epileptic medications . a diagnosis of mental retardation complicated by epilepsy was made , and his development was noted to be markedly delayed . he raised his head at age 7 months , sat up at 26 months , and had not yet acquired the ability to stand . he had a flat and mid - hypoplastic face with prognathism , narrow and upward slanting palpebral fissures with hypertelorism , low - set ears , a small crashed nose , widely spaced incisors , carp - like mouth , and round back ( fig .1 ) . he demonstrated repeated stereotyped behavior like hitting his chin with his palm ; this behavior was often associated with emotional outbursts . soon after admission , a generalized tonic - clonic type seizure was started and lasted approximately one hour ; at that time his vital signs were as follows : blood pressure 100/60 mmhg , pulse rate 138 bpm , respiration rate 32 bpm , and body temperature 38.5 . mild throat injection was seen , but other systemic examinations were normal . on neurologic exam , mental status was alert , all cranial nerve exams were normal , and muscle tone in both extremities were decreased to grade iv / iv bilaterally but all deep tendon reflexes were physiologic . initial laboratory investigations revealed : hemoglobin 12.7 g / dl , platelet count 374,000 / l and white blood cell count 11,780 / l . the c - reactive protein was slightly elevated at 19.0 mg / dl on the day of admission and returned to normal 3 days later . a sleep electroencephalogram revealed intermittent high - amplitude slow wave discharges from the temporo - occipital area , representing mild cerebral dysfunction . on radiologic evaluation , spine radiography revealed mild scoliosis . the characteristic facial features and mental retardation of the patient led us to consider atr - x syndrome ; thus , peripheral rbcs were screened for hemoglobin h ( hbh ) inclusion bodies . hbh inclusions were detected under the microscope in 1.1 % of brilliant cresyl blue stained rbcs , consistent with the diagnosis of atr - x syndrome ( fig . the patient 's father , mother and two sisters were all given the same test ; only his mother and eldest sister had the same findings . genomic dna from the peripheral blood of our patient and his 4 family members was extracted with the wizard genomic dna purification kit ( promega , madison , wi , usa ) and used as a template for amplification of the atrx gene . polymerase chain reaction ( pcr ) was separated into three parts and carried out with sequence - specific oligonucleotide primers containing 20 known major mutation sites ( table 1 , figs . 3 , 4 ) . pcr amplification using each primercycling conditions were one cycle at 95 for 5 min , followed by 35 cycles of 95 for 30 sec , at an annealing temperature adjusted to each primer 's ( tm ) for 30 sec , 72 for 30 sec , followed by one cycle at 72 for 7 min . for direct sequencing , the pcr products were purified using a pcr clean - up system offered by promega . dna sequencing was performed using the purified pcr products as template , the same primers as those used for template generation , the bigdye terminator cycle sequencing ready reaction kit ( applied biosystems , foster city , ca , usa ) , and automatic sequencer abi prism 3730 xl dna analyzer ( applied biosystems , foster city , ca , usa ) . sequence data were assembled and compared to that of a previously reported atrx sequence from accession number z84487 using the dnastar software ( dnastar inc . , madison , wi , usa ) . mutation analysis for our patient showed a point mutation on the 9th exon in the atrx gene of thymine to cytosine so that trp ( c ) , the 220th amino acid , was replaced by ser ( r ) ( fig . we investigated the same mutation in his 4 family members , and his mother and two sisters were found to be carriers . the x - linked - thalassemia mental retardation syndrome is a serious recessive disorder resulting from mutations in the atrx gene , mapping in xq13 .3 and coding for a protein containing the signature motif of the snf2 family of atpases . members of this protein family are thought to act generally as part of large multi - protein complexes and impart on those complexes the ability to utilize the energy of atp hydrolysis to remodel the structure of chromatin and thereby regulate protein / dna interactions ( 11 ) . this disease is very rare , probably with an incidence of less than 1/100 ,000 live - born males ( 11 ) . affected males present with severe mental retardation , a typical facial appearance , microcephaly , urogenital anomalies , and an atypical form of - thalassemia . pregnancy is usually uneventful , proceeds to term , and , in 90 % of cases , birth weight is normal . affected neonates usually have marked hypotonia and associated feeding difficulties . in early childhood , all milestones are delayed . as the affected individuals grow older , there is often a tendency toward spasticity . a number of patients have reportedly had jerking movements that are not associated with epileptiform activity on eeg . brain imaging studies frequently show no abnormality , although mild cerebral atrophy or agenesis of the corpus callosum may be seen . the distinctive facial traits are most readily recognized in early childhood : the frontal hair is often upswept ; there is telecanthus , epicanthic folds , midface hypoplasia , and a small , triangular , upturned nose . the upper lip is tented and the lower lip is full and everted , giving the mouth a " carp - like " appearance . the frontal incisors are frequently widely spaced , and the tongue protrudes . genital abnormalities are seen in 80 % of these children . a wide range of relatively mild skeletal abnormalities have been noted . the tendency to aspiration is commonly implicated as a cause of death in early childhood . constipation is common and in some individuals is a major problem to manage . a wide range of cardiac and renal abnormalities also has been noted . there is considerable variation in the hematologic manifestations associated with atrx mutations ( 11 ) . a number of families have been identified in which some or all of the affected members have no signs of - thalassemia ; despite lack of these signs , however , diagnosis of - thalassemia requires only a simple investigation . they are intellectually normal and have no consistent physical manifestations , because they show preferential inactivation of the mutated x - chromosome . rare cells with hbh inclusions may be found in approximately one fourth of obligate carriers ( 12 ) . in our case , there were hbh inclusions in 2 of 3 carriers . but recently , there have been some cases of females with atrx mutations with phenotypical abnormalities . ( 13 ) reported a carrier mother who showed non - skewed x - inactivation with moderate mental retardation . ( 14 ) described a 4 - yr - old girl with typical features of atr - x syndrome , carrying the recurrent r246c mutation of atrx . they showed that her pattern of x - inactivation was totally skewed and that her active x chromosome , which harbors the atrx mutation , was maternally inherited . we report the first korean case of atr - x syndrome in a 32 - month - old boy . now , we can consider atr - x syndrome in a young male child with characteristic facial features and neurologic abnormalities of unknown etiology , and get simple screening test for hbh inclusions so that adequate and early management should be started .
output:
