Alpha-thalassemia intellectual disability: variable phenotypic expression among males with a recurrent nonsense mutationÂ -Â c.109C>T (p.R37X).

[alpha-thalassemia]

Alpha-thalassemia intellectual disability , one of the recognizable X-linked disability syndromes , is characterized by short stature , microcephaly , distinctive facies , hypotonic appearance , cardiac and genital anomalies , and marked skewing of X-inactivation in female carriers . With the advent of next generation sequencing , mutations have been identified that result in less severe phenotypes lacking one or more of these phenotypic manifestations . Here we report five unrelated kindreds in which a c .109 C >T (p .R 37 X ) mutation segregates with a variable but overall milder phenotype . The distinctive facial appearance of alpha-thalassemia intellectual disability was present in only one of the 18 affected males evaluated beyond the age of puberty , although suggestive facial appearance was present in several during infancy or early childhood . Although the responsible genetic alteration is a nonsense mutation in exon 2 of ATRX , the phenotype appears to be partially rescued by the production of alternative transcripts and /or other molecular mechanisms .

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Diseases presenting "other molecular mechanisms" symptom

alpha-thalassemia

proteus syndrome

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