Short stature and growth hormone deficiency in a subset of patients with <scp>Potocki–Lupski</scp> syndrome: Expanding the phenotype of <scp>PTLS</scp>

Franciskovich, Rachel; Soler‐Alfonso, Claudia; Neira‐Fresneda, Juanita; Lupski, James R.; McCann‐Crosby, Bonnie; Potocki, Lorraine

doi:10.1002/ajmg.a.61741

Cited by 7 publications

(4 citation statements)

References 30 publications

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“…Human chromosome 17 is a small, gene‐rich chromosome associated with several well‐known duplication syndromes. So far the duplication region of 17p13.3p11.2 includes chromosome 17p13.3 duplication syndrome[OMIM:613215], 20 Charcot Marie Tooth Syndrome Type 1A (CMT1A), 21 and Potocki Lupski syndrome (17p11.2 duplication syndrome) 22 . Among these, 17p13.3 duplication syndrome 23 and Potocki‐Lupski syndrome 22 were reported to be related with CCA.…”

Section: Discussionmentioning

confidence: 99%

Prenatal genetic testing in 19 fetuses with corpus callosum abnormality

She

Tang

Cui

et al. 2021

Clinical Laboratory Analysis

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Background Corpus callosum abnormality (CCA) can lead to epilepsy, moderate severe neurologic or mental retardation. The prognosis of CCA is closely related to genetic etiology. However, copy number variations (CNVs) associated with fetal CCA are still limited and need to be further identified. Only a few scattered cases have been reported to diagnose CCA by whole exome sequencing (WES). Methods Karyotyping analysis, copy number variation sequencing (CNV‐seq), chromosomal microarray analysis (CMA) and WES were parallelly performed for prenatal diagnosis of 19 CCA cases. Results The total detection rate of karyotyping analysis, CMA (or CNV‐seq) and WES were 15.79% (3/19), 21.05% (4/19) and 40.00% (2/5), respectively. Two cases (case 11 and case 15) were diagnosed as aneuploidy (47, XY, + 13 and 47, XX, + 21) by karyotyping analysis and CNV‐seq. Karyotyping analysis revealed an unknown origin fragment (46,XY,add(13)(p11.2)) in case 3, which was further confirmed to originate from p13.3p11.2 of chromosome 17 by CNV‐seq. CMA revealed arr1q43q44 (238923617–246964774) × 1(8.04 Mb) in case 8 with a negative result of chromosome karyotype. WES revealed that 2 of 5 cases with negative results of karyotyping and CNV‐seq or CMA carried pathogenic genes ALDH7A1 and ARID1B. Conclusion Parallel genetic tests showed that CNV‐seq and CMA are able to identify additional, clinically significant cytogenetic information of CCA compared to karyotyping; WES significantly improves the detection rate of genetic etiology of CCA. For the patients with a negative results of CNV‐seq or CMA, further WES test is recommended.

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Section: Discussionmentioning

confidence: 99%

Prenatal genetic testing in 19 fetuses with corpus callosum abnormality

She

Tang

Cui

et al. 2021

Clinical Laboratory Analysis

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“…Although the underlying pathogenesis of GHD developmental defects is associated with pituitary dysplasia, Sella dysplasia and GH-IGF1 axis gene mutations, most genetic causes of GHD have not been identified, which may lead a certain false-negative rate in diagnostic approach. Recently, it has been reported that some patients with Potocki-Lupski syndrome or Prader-Willi syndrome have similar phenotypes as GHD patients ( 33 , 34 ), and recessive mutations in RNPC3 could also lead to the occurrence and development of GHD ( 35 ). In our study, we found seven genes ( PTPN11 , ROR2 , ACAN , COL11A1 , TRPS1 , IDS , MMP13 ) might associate with dysfunction of GH-IGF axis, indicating GHD may exist in a variety of Mendelian syndromes.…”

Section: Discussionmentioning

confidence: 99%

Whole Exome Sequencing Uncovered the Genetic Architecture of Growth Hormone Deficiency Patients

Xie

Zhao

et al. 2021

Front. Endocrinol.

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PurposeCongenital growth hormone deficiency (GHD) is a rare and etiologically heterogeneous disease. We aim to screen disease-causing mutations of GHD in a relatively sizable cohort and discover underlying mechanisms via a candidate gene-based mutational burden analysis.MethodsWe retrospectively analyzed 109 short stature patients associated with hormone deficiency. All patients were classified into two groups: Group I (n=45) with definitive GHD and Group II (n=64) with possible GHD. We analyzed correlation consistency between clinical criteria and molecular findings by whole exome sequencing (WES) in two groups. The patients without a molecular diagnosis (n=90) were compared with 942 in-house controls for the mutational burden of rare mutations in 259 genes biologically related with the GH axis.ResultsIn 19 patients with molecular diagnosis, we found 5 possible GHD patients received known molecular diagnosis associated with GHD (NF1 [c.2329T>A, c.7131C>G], GHRHR [c.731G>A], STAT5B [c.1102delC], HRAS [c.187_207dup]). By mutational burden analysis of predicted deleterious variants in 90 patients without molecular diagnosis, we found that POLR3A (p = 0.005), SUFU (p = 0.006), LHX3 (p = 0.021) and CREB3L4 (p = 0.040) represented top genes enriched in GHD patients.ConclusionOur study revealed the discrepancies between the laboratory testing and molecular diagnosis of GHD. These differences should be considered when for an accurate diagnosis of GHD. We also identified four candidate genes that might be associated with GHD.

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“…In daily clinical practice, the question of growth deficiency predictably arises in children with common genetic disorders such as Turner syndrome, Down syndrome, and Noonan syndrome [ 19 ], or better known diseases as Diamond-Blackfan anaemia [ 20 ]. The diagnosis of growth deficiency due to growth hormone deficiency (GHD) in children with other genetic disorders is challenging, partly due to the lack of a true gold standard, and the relatively poor correlation of growth and the genes residing in the critical chromosomal locus [ 21 ].SDS is a rare disease without a well-defined prevalence. Severe growth retardation (particularly in length/ height) is one of its typical features, which can be alleged to be linked to the genetic cause of the disease [ 11 , 13 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Growth hormone improves short stature in children with Shwachman-Diamond syndrome

Bogusz-Wójcik¹,

Kołodziejczyk²,

Moszczyńska³

et al. 2021

pedm

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Introduction Shwachman-Diamond syndrome (SDS) is a rare, autosomal recessive multisystemic disorder characterized by pancreatic insufficiency and bone marrow failure. Short stature is a recognized feature of SDS syndrome; however, systemic data concerning recombinant human growth hormone (rGH) treatment are limited. Aim of the study To assess the effect of rGH treatment in patients with SDS. Material and Methods Retrospective data were collected from patients with SDS and growth hormone deficiency (GHD) treated with rGH in the Children’s Memorial Health Institute in Warsaw. The annual growth velocity (GV) and height standard deviation score (SD) were compared for up to 2 years of rGH treatment. Results Six SDS patients (M : F = 1 : 5) treated with rGH were identified. The median age of starting rGH therapy was 7.5 years, with a mean baseline height SD of –4.06 (range: –6.3 to –2.3 SD). The height SD significantly improved to –3.3 ( p = 0.002) and then –3.03 ( p = 0.002), following 1 and 2 years of treatment, respectively. The average GV for the patients prior to starting treatment was 4.9 cm/year (range: 3.1–6.5 cm/year), which significantly improved to 7.6 cm/year (range: 5.7–9.6 cm/year) after 1 year of rGH treatment ( p = 0.020) and to 6.7 cm/year at the end of 2 years. Conclusions Our study has shown that rGH treatment significantly improves the height SDS and GV of patients with SDS and GHD without any side effects. Further research is required to analyse the long-term effect of rGH therapy in patients with SDS.

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Short stature and growth hormone deficiency in a subset of patients with Potocki–Lupski syndrome: Expanding the phenotype of PTLS

Cited by 7 publications

References 30 publications

Prenatal genetic testing in 19 fetuses with corpus callosum abnormality

Prenatal genetic testing in 19 fetuses with corpus callosum abnormality

Whole Exome Sequencing Uncovered the Genetic Architecture of Growth Hormone Deficiency Patients

Growth hormone improves short stature in children with Shwachman-Diamond syndrome

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