Clinical, cytogenetic, and molecular characterization of six patients with ring chromosomes 22, including one with concomitant 22q11.2 deletion

Abstract

We report here on six patients with a ring chromosome 22 and the range of cytogenetic and phenotypic features presented by them. Genomic analysis was carried out using classical and molecular cytogenetics, MLPA (Multiplex Ligation-dependent Probe Amplification) and genome-wide SNP-array analysis. The ring was found in all patients, but Patient 6 displayed constitutional mosaicism with a normal cell line. Five patients had deletions in the ring chromosome 22, and in four of them the breakpoints--unique for each patient--could be identified by genome-wide SNP-array analysis. One patient presented with a 22q11.2 deletion concomitant with the deletion caused by the ring formation. Common phenotypic features included autism, speech delay and seizures, as previously reported for individuals with r(22) and/or 22q13.3 deletions. Investigation of the genes within the deletions revealed multiple genes related to development of the central nervous system, psychomotor delay, severe language impairment, hypotonia, and autistic symptoms. There was no clear correlation between the severity of clinical features and the size of the deleted segment. This study underscores the variability in ring structure and clinical presentation of the r(22) and adds information to the limited literature on this rare disorder.

Mosaicism for structural non-centromeric autosomal rearrangements in disease-defined carriers: sex differences in the rearrangements profile and maternal age distributions

“…In 17 cases of monosomy of 18q12.3 one was a mosaic with a normal cell line [15]. Among 29 carriers of ring chromosomes, three had a normal cell line [16], and among six patients with a r(22), one was mosaic for a normal cell line [17]. In 1966–1991, 10 patients with r(18) were diagnosed among 82,000 patients karyotyped for constitutional reasons; three of these 10 presented with mosaicism for normal line [18].…”

Formigas Como Vetor De Propagação Bacteriana No Conjunto Hospitalar De Sorocaba – Sp

“…A correlação genótipo-fenótipo em PMS é importante para delinear genes e vias biológicas relacionadas com esta síndrome (Soorya et al, 2018). linear e os achados clínicos mais frequentes são: retardo no crescimento intrauterino e pós-natal, deficiência intelectual, atraso de fala severo ou ausente, atraso no desenvolvimento motor, microcefalia, orelhas grandes e deformadas, hipertelorismo, estrabismo, pregas epicânticas, ptose dos lábios superiores, sobrancelhas espessas, ponte nasal larga e deprimida, mandíbula curta, má oclusão e posição irregular dos dentes, palato alto, clinodactilia de 5° dedo, sindactilia parcial entre o 2º e 3º dedos, hipotonia, convulsões e alterações de comportamento, transtornos do espectro autista e unhas dos pés hipoplásicos (Guilherme et al, 2014;Jeffries et al, 2005;Ishmael et al, 2003;Maclean et al, 2000;Schinzel, 2001;De Mas et al, 2002). Na tabela 1 nós apresentamos as características clínicas mais comuns observadas em portadores de r (22) Os tumores teratóides/rabdóides atípicos (AT/RT) do Sistema Nervoso Central são raros, altamente malignos, presentes em 2-3% dos tumores cerebrais pediátricos e têm sido previamente descritos em pacientes com r (22) (Biegel, 1999;Cho et al, 2014) e síndrome de Phelan-McDermid (Sathyamoorthi et al, 2009;De Amorim Bernstein et al, 2013).…”

“…Um grupo distinto de monossomias 22q13 é resultante da formação de um cromossomo 22 em anel [r (22)]. O r(22) tem sido descrito em mais de 60 pacientes com PMS (Hannachi et al, 2013), permanecendo incerto se a variabilidade fenotípica é consequência da perda do material cromossômico ou instabilidade do anel devido ao mosaicismo celular (Guilherme et al, 2014). As características clínicas do r (22) se sobrepõem com as observadas naqueles que apresentam deleção terminal 22q13 e, em ambas as síndromes, o gene SHANK3 é sugerido como candidato para as características neurocomportamentais (Luciani et al, 2003).…”

Clinical Reasoning: A common cause for Phelan-McDermid syndrome and neurofibromatosis type 2

“…There are multiple reports of patients with ring chromosome 22, all of whom shared features of PMS, including speech delay, seizures, and autism. 9 Rearrangements of chromosome 22, including ring 22, have also been reported to cause NF2. 10 In the case of ring chromosome 22 due to a large, terminal deletion like in our patient, cells become monosomic for chromosome 22, and then have only 1 copy of NF2.…”