A 45,X/46,XY DSD (Disorder of Sexual Development) case with an extremely uneven distribution of 46,XY cells between lymphocytes and gonads

Nomura, Risa; Miyai, K; Okada, Michiyo; Kajiwara, Michiko; Ono, Masafumi; Ogata, Tsutomu; Onishi, Iichiroh; Sato, Mana; Shimizu, Masaki; Akashi, Takumi; Mizutani, Shuki; Kashimada, Kenichi

doi:10.1297/cpe.24.11

Cited by 7 publications

(7 citation statements)

References 9 publications

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“…However, we should take into account that the mean of age in our short cohort was 8.6 years so probably the majority of patients did not manifest skeletal deformities at the time. Hypospadia, hypogonadism, and ambiguous genitalia are more obligate sign for mosaics 45,X/46,XY or 45,X/46,Xidic(Y)(q11.2) than short stature (Hes et al, 2009;Kaprova-Pleskacova et al, 2013;Nomura et al, 2015). Thus we detected significant correlation in patient with aberration of sex chromosomes (p < 0.01) but it was not detected in patients with CNV variants of SHOX.…”

Section: Discussionmentioning

confidence: 49%

Short stature and SHOX (Short stature homeobox) variants—efficacy of screening using various strategies

Capkova

Rosenberger

et al. 2020

PeerJ

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Background SHOX mutations have previously been described as causes of Léri-Weill dyschondrosteosis (LWD), Langer mesomelic dysplasia (LMD), and idiopathic short stature. The loss of X chromosome—Turner syndrome or mosaic 45,X/46,XX or 46,XY—also leads to the heterozygous loss of SHOX in patients with short stature only or with features similar to LWD. The aim of this study was to assess the efficacy of the targeted screening for SHOX variants, which involved different methods in the laboratory analysis of short stature. We determined the significance and positive predictive value of short stature for the detection of SHOX variants. Methods Targeted screening for variants in SHOX involving MLPA, sequencing, karyotyping and FISH was performed in the short stature cohort (N = 174) and control cohort (N = 91). The significance of short stature and particular characteristics for the detection of SHOX variants was determined by Fisher’s exact test, and the probability of SHOX mutation occurrence was calculated using a forward/stepwise logistic regression model. Results In total, 27 and 15 variants influencing SHOX were detected in the short stature and control cohorts, respectively (p > 0.01). Sex chromosome aberrations and pathogenic CNV resulting in diagnosis were detected in eight (4.6%) and five (2.9%) patients of the short stature group and three (3.3%) and one (1.1%) individuals of the control group. VUS variants were discovered in 14 (8.0%) and 11 (12.1%) individuals of the short stature and control groups, respectively. MLPA demonstrated the detection rate of 13.22%, and it can be used as a frontline method for detection of aberrations involving SHOX. However, only mosaicism of monosomy X with a higher frequency of monosomic cells could be reliably discovered by this method. Karyotyping and FISH can compensate for this limitation; their detection rates in short stature group were 3.55% and 13.46% (N = 52), respectively. FISH proved to be more effective than karyotyping in the study as it could reveal cryptic mosaics in some cases where karyotyping initially failed to detect such a clone. We suggest adding FISH on different tissue than peripheral blood to verify sex-chromosome constitution, especially in cases with karyotypes: 45,X; mosaic 45,X/46,XX or 46,XY; 46,Xidic(Y) detected from blood; in children, where mosaic 45,X was detected prenatally but was not confirmed from peripheral blood. The correlation of short stature with the occurrence of SHOX mutations was insignificant and short stature demonstrates a low positive predictive value-15.5% as unique indicator for SHOX mutations. The typical skeletal signs of LWD, including Madelung deformity and disproportionate growth, positively correlate with the findings of pathogenic SHOX variants (p < 0.01) by Fisher’s exact test but not with the findings of VUS variants in SHOX which are more prevalent in the individuals with idiopathic short stature or in the individuals with normal height.

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Section: Discussionmentioning

confidence: 49%

Short stature and SHOX (Short stature homeobox) variants—efficacy of screening using various strategies

Capkova

Rosenberger

et al. 2020

PeerJ

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“…Nevertheless clinical phenotype is not correlated with the percentage of 45,X cells on lymphocytic karyotype (6,7,8). Factors determining the distribution of 45,X cells are unknown (19). In the gonads, it has been suggested that gonadal differentiation depends on the percentage of 45,X cells colonizing the urogenital ridge during embryogenesis (4,20).…”

Section: Discussionmentioning

confidence: 99%

Should 45,X/46,XY boys with no or mild anomaly of external genitalia be investigated and followed up?

Dumeige

Chatelais

Bouvattier

et al. 2018

European Journal of Endocrinology

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This study emphasizes the need to identify and follow-up 45,X/46,XY patients born with normal male phenotype until adulthood, as they present similar prognosis than those born with severe genital anomalies. Currently, most patients are diagnosed in adulthood with azoospermia, consistent with our observations of decreased testicular function at the end of puberty. Early management of these patients may lead to fertility preservation strategies.

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“…Mosaicism involving 45,X/46,XY can be associated with a spectrum of phenotypes ranging from typical female (with a low proportion of 46,XY) or typical male (with a low proportion of 45,X), to males with hypogonadism or ambiguous genitalia. For this reason, the term “male Turner syndrome” should be avoided, and individuals can be referred to as having mixed gonadal dysgenesis, or simply mosaicism for 45,X/46,XY (Lindhardt Johansen et al, ; Nomura et al, ; Wu et al, ).…”

Section: Geneticsmentioning

confidence: 99%

Recognition and management of adults with Turner syndrome: From the transition of adolescence through the senior years

Lin

Prakash

Andersen

et al. 2019

American J of Med Genetics Pt A

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Turner syndrome is recognized now as a syndrome familiar not only to pediatricians and pediatric specialists, medical geneticists, adult endocrinologists, and cardiologists, but also increasingly to primary care providers, internal medicine specialists, obstetricians, and reproductive medicine specialists. In addition, the care of women with Turner syndrome may involve social services, and various educational and neuropsychologic therapies. This article focuses on the recognition and management of Turner syndrome

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A 45,X/46,XY DSD (Disorder of Sexual Development) case with an extremely uneven distribution of 46,XY cells between lymphocytes and gonads

Cited by 7 publications

References 9 publications

Short stature and SHOX (Short stature homeobox) variants—efficacy of screening using various strategies

Short stature and SHOX (Short stature homeobox) variants—efficacy of screening using various strategies

Should 45,X/46,XY boys with no or mild anomaly of external genitalia be investigated and followed up?

Recognition and management of adults with Turner syndrome: From the transition of adolescence through the senior years

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