Abstract
BackgroundAutosomal recessive intellectual disabilities, syndromic and non-syndromic, are of specific importance in consanguineous communities. High throughput sequencing technologies have enhanced diagnosing the Mendelian forms of intellectual disability. Mental retardation 36 and 38 are emerging clinical entities with variable presentations that extend beyond adaptive and intellectual functioning. MethodsWe used exome sequencing, bioinformatic tools and Sanger sequencing to diagnose two Sudanese families with syndromic intellectual disability. ResultsWe identified the variant NM_138422.3 (ADAT3):c.430G>A (rs730882213) in a homozygous state in two female siblings manifesting a clinical phenotype consistent with mental retardation 36. This variant was previously identified as pathogenic founder variant in multiple families from the Middle East manifesting mental retardation 36. Our patients had bullet-shaped distal phalanges, expanding the previously reported presentation. In a second family, the proband had a clinical phenotype consistent with mental retardation 38. Genetic analysis revealed the novel homozygous variant NM_004667.4 (HERC2):c.10855C>T as the potential culprit. In addition to what has been reported previously, the proband had cleft lip and palate, bulbous nose, spastic lower limbs and stones in his gallbladder.Conclusion Herein, we corroborated and extended the previously reported phenotypic spectrums associated with autosomal recessive mental retardation 36 and 38.
Riegel M, Schinzel A. 2002. Duplication of (2)(q11.1-q13.2) in a boy with mental retardation and cleft lip and palate: another gene locus on proximal 2q? Am J Med Genet 111:76-80
