Deletion mapping by FISH with BACs in patients with partial monosomy 22q13

Abstract

Patients with deletions in 22q13 are known to have phenotypic features that include normal or accelerated growth, large hands and feet, hypotonia, delayed psychomotor development and mild facial dysmorphism. To date, very few cases have been investigated by detailed molecular genetic analysis. We have analyzed three new patients with terminal deletions in 22q. We compared the cytogenetic observations with molecular data assessed by fluorescence in situ hybridization and an array of characterized bacterial artificial chromosome recombinants. The shortest region of deletion overlap is localized in 22q13.2-qter distal to the marker D22S94, but the telomeric repeat in the deleted chromosome appears to remain intact. When parental alleles were investigated in two of the three patients, the aberrant homolog was found to be of paternal origin in both cases. Although the deleted region still spans >20 cM, molecular analysis of additional patients and screening for new genes might help in elucidating candidate genes connected with the dysmorphisms defined by deletions of 22q13.

Girl with accelerated growth, hearing loss, inner ear anomalies, delayed myelination of the brain, and del(22)(q13.1q13.2)

“…The result of FISH analysis and normal activity of arylsulfatase A in the lymphocytes, the gene of which is mapped to chromosome 22q13.3 [Geurts van Kessel et al, 1980;Narahara et al, 1992] indicate that a 22q13.3 segment is not deleted in her chromosome. Among the 18 previously reported patients with 22q13 (22)(q13.1q13.2) and Accelerated Growthdeletion [Herman et al, 1988;Romain et al, 1990;Zwaigenbaum et al, 1990;Narahara et al, 1992;Phelan et al, 1992;Nesslinger et al, 1994;Dohney et al, 1997;Wong et al, 1997;Schröder et al, 1998], there has been only one patient who had an interstitial deletion of a 22q13 segment [Romain et al, 1990] and no case of interstitial deletion involving a 22q13.1-q13.2 segment, as seen in our patient.…”

“…To our knowledge, however, deletion of 22q13 band has been reported in only 18 patients [Herman et al, 1988;Romain et al, 1990;Zwaigenbaum et al, 1990;Narahara et al, 1992;Phelan et al, 1992;Nesslinger et al, 1994;Dohney et al, 1997;Wong et al, 1997;Schröder et al, 1998]. All of them were a terminal deletion involving 22q13, but only one had interstitial deletion of this segment [Romain et al, 1990].…”

The 22q13.3 Deletion Syndrome (Phelan-McDermid Syndrome)

“…Both deletions occurred on the paternal chromosome 22. Schroder et al [1998] reported 3 unrelated individuals with bilateral hearing loss, possibly contributing to speech delay. Two of the 3 patients had renal abnormalities.…”

Newborn infant with inherited ring and de novo interstitial deletion on homologous chromosome 22s

“…The breakpoint involving loss of short arm material is of no clinical consequence, whereas breakpoint on the long arm, which can vary in size, can affect the phenotypic expression dependent on the size of the deletion. Manifestations of 22q telomere deletions include developmental delay, normal or accelerated growth, hypotonia, delay or absence of speech, and minor facial anomalies [Doheny et al, 1997;Nesslinger et al, 1994;Schroder et al, 1998], which is similar to the phenotype reported for ring 22 [Hunter et al, 1977].…”

“…Although the phenotypes for both of these conditions are variable, the occurrence of hemizygosity for both of these regions in our patient present as a relatively mild phenotype. Hunter et al, 1977;Stoll and Roth, 1983; a breakpoint is proximal to D22S39 phenotype: Nesslinger et al, 1994;Doheny et al, 1997;Schroder et al, 1998;Precht et al, 1998; interstitial deletion 22q11.2: Demczuk and Aurias, 1995;Leana-Cox, 1996;Ryan et al, 1997. …”