Molecular and clinical characterization of patients with overlapping 10p deletions.
Chromosome 10p terminal deletions have been associated with DiGeorge phenotype, and within the same genomic region haploinsufficiency of GATA3 causes the HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia). We have performed detailed molecular analysis of four patients with partial overlapping 10p deletions by using FISH-mapping, array-CGH, and custom-designed high-resolution oligonucleotide array. All four patients had mental retardation and speech impairment and three of them showed variable signs of HDR syndrome. In addition, two patients had autistic behaviors and had similar dysmorphic features giving them a striking physical resemblance. A review of the literature identified 10 previously published cases with similar 10p deletions and reliable molecular or molecular cytogenetic mapping data. The combined information of present and previous cases suggests that partial deletions of 10p14-p15 represent a syndrome with a distinct and more severe phenotype than previously assumed. The main characteristics include severe mental retardation, language impairment, autistic behavior, and characteristic clinical features. A critical region involved in mental retardation and speech impairment is defined within 1.6 Mb in 10p15.3. In addition, deletion of 4.3 Mb within 10p14 is associated with autism and characteristic clinical findings.
Lindstrand
Anna
A
Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. anna.lindstrand@ki.se
Malmgren
Helena
H
Verri
Annapia
A
Benetti
Elisa
E
Eriksson
Maud
M
Nordgren
Ann
A
Anderlid
Britt-Marie
BM
Golovleva
Irina
I
Schoumans
Jacqueline
J
Blennow
Elisabeth
E
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy