Molecular genetic delineation of 2q37.3 deletion in autism and osteodystrophy: report of a case and of new markers for deletion screening by PCR

Abstract

Abstract.We recently studied a patient who meets criteria for autistic disorder and has a 2q37 deletion. Molecular cytogenetic studies were carried out using DNA isolated from 22 different 2q37 mapped BACs to more precisely define the extent of the chromosome deletion. We also analyzed 2q37 mapped polymorphic markers. In addition DNA sequences of BACs in the deletion region were scanned to identify microsatellite repeats. We describe four new polymorphic microsatellite repeat markers in the 2q37.3 region. These markers enabled us to determine the parental origin of the deletion in our patient. DNA from 8-13 unrelated individuals was used to determine heterozygosity estimates for these markers. We review four genes deleted in our patient -genes whose known functions and sites of expression in the brain and/or bone make them candidates for involvement in autism and/or the osteodystrophy observed in patients with 2q37.3 deletions.

The 2q37-deletion syndrome: an update of the clinical spectrum including overweight, brachydactyly and behavioural features in 14 new patients

“…20,23 Most of the patients in our study had heterogeneous behavioural disorders, with seven in the autistic spectrum, and patients P4 and P11 were reported as being autistic. The 'behaviour' map shows that all affected patients shared a deletion of the following candidate genes: TWIST2, HDAC4, 10 KIF1A, 15 PASK, 5 HDLBP, 5 FARP2, 5 and ATG4B. P14 (del/dup 2q37.3) showed normal behaviour but carried deletions of the same candidate genes, except for HDAC4 and TWIST2.…”

“…Interestingly, P5 had a similar deletion but no behavioural problems. KIF1A, highlighted by the literature 15 and Manteia, encodes a motor protein involved in the anterograde transport of synaptic-vesicle precursors along axons, and a mutation in this gene has been reported in a patient with nonsyndromic intellectual disability (MIM 601255). KIF1A is also associated with hypoactivity and hyporesponse to tactile stimuli in knockout mice (Manteia).…”

“…[1][2][3][4][5][6][7][8][9][10] At least 197 genes are located in the 2q37 region (230.7-243.2 Mb; Hg19; NCBI map viewer http://www.ncbi.nlm.nih.gov/mapview/). Of these, 11 have been reported as being potentially related to the 2q37-deletion phenotype so far, 5,[10][11][12][13][14][15][16][17] but the phenotypic implications of most of them remain unknown. Among the candidate genes with a known phenotype, HDAC4 has notably been established as being responsible for brachymetaphalangy and intellectual disability.…”

Phenotypic variant of Brachydactyly-mental retardation syndrome in a family with an inherited interstitial 2q37.3 microdeletion including HDAC4

“…To evaluate further diagnostic criteria for the 2q37 deletion syndrome, we compared the clinical findings of our patients and a representative cohort of other published patients carrying HDAC4 mutations or overlapping interstitial or terminal 2q37 deletions ( Figure 3, Table 1). 3,5,[15][16][17][18][19][20][21][22][23][24] The female to male ratio was 21/6. Regarding the body measurements, 4/18 of the patients were microcephalic, 8/24 revealed a short stature and 7/20 an overweight.…”

Molecular genetics of autism spectrum disorders

“…Numerous studies have revealed that several cases of autism have been associated with chromosomal abnormalities such as deletion, duplication, balanced, unblanced and complex translocations (Yu et al 2002;Smith et al 2000;Thomas et al 1999;Vostanis et al 1994;Michaelis et al 1997;Nurmi et al 2001;Burd et al 1998;Ghazziuddin and Burnmeister 1999;Smith et al 2001;Gillberg et al 1991;Yan et al 2000;Vincent et al 2001;Tentler et al 2001;Wolpert et al 2001). Although in some cases deletions ranged from 5 to 260 kb and patients exhibited a varying degree of intellectual impairments (Bolton et al 2001a), there is no clustering of breakpoints involved and deletions are scattered throughout the genome.…”