Mental Retardation, Truncal Obesity, Retinal Dystrophy, And Micropenis Syndrome

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

INPP5E, BBS5

Drugs

Adeno-associated virus serotype 8 containing the human RdCVF sequence and the human RdCVFL sequence, Combination of three adeno-associated viral vectors of serotype 8 containing the 5'-, the body- and the 3'- coding sequences of human CEP290 fused to inteins

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A number sign (#) is used with this entry because of evidence that a syndrome of mental retardation, truncal obesity, retinal dystrophy, and micropenis syndrome (MORMS) is caused by homozygous mutation in the INPP5E gene (613037) on chromosome 9q34. One such family has been reported.

Clinical Features

Hampshire et al. (2006) reported a consanguineous Pakistani kindred in which 14 individuals were affected with an autosomal recessive disorder characterized by moderate mental retardation, truncal obesity, congenital nonprogressive retinal dystrophy, and micropenis in males. The authors suggested the acronym 'MORM' syndrome. The phenotype was similar to Bardet-Biedl syndrome (BBS; 209900) and Cohen syndrome (COH1; 216550) but could be distinguished by the age of onset and nonprogressive nature of the visual impairment, and the lack of several characteristics, including dysmorphic facies, skin or gingival infection, microcephaly, 'mottled retina,' polydactyly, and testicular anomalies. The family originated from a valley in the Salt Range of Punjab, Pakistan. Family lore maintained that 16 Arabs settled in the valley 1,000 years ago and that descendants had always married within the family since that time. The village currently numbers about 5,000 with 5 different clans; the affected pedigree is a subgroup of 1 of these 5 clans, and affected individuals could be traced back to 1 founding couple.

Mapping

By genomewide linkage analysis, Hampshire et al. (2006) identified a candidate MORM syndrome locus within an approximately 1-cM subtelomeric region on chromosome 9q34.3 (maximum lod score of 5.64) between markers D9S158 and D9S905.

Molecular Genetics

In affected members of a family with MORM syndrome, Jacoby et al. (2009) identified a homozygous mutation (Q627X; 613037.0001) in the INPP5E gene. In vitro functional expression studies showed that the mutant protein had impaired localization in cilia and was unable to stabilize ciliary structures. However, phosphatase activity was retained.