Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation

Baquero-Montoya, Carolina; Gil-Rodríguez, María-Concepción; Hernández-Marcos, María; Teresa-Rodrigo, María-Esperanza; Vicente-Gabas, Alicia; Bernal, M. R. Valero; Casale, César H.; Bueno-Lozano, Gloria; Bueno-Martínez, Inés; Queralt, Ethel; Villa, Olaya; Hernando‐Davalillo, Cristina; Armengol, Lluı́s; Gómez‐Puertas, Paulino; Puisac, Beatriz; Selicorni, Angelo; Ramos, Feliciano J.; Pié, Juan

doi:10.1016/j.ejmg.2014.05.006

Cited by 8 publications

(10 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the limbs of the left side were completely normal (Table ; Fig. , P1 i–iv) [Baquero‐Montoya et al, ]. Surprisingly, despite the serious unilateral limb reduction defect the patient had only mild neurocognitive impairment [Gillis et al, ; Kline et al, ].…”

Section: Special Casesmentioning

confidence: 99%

“…Surprisingly, despite the serious unilateral limb reduction defect the patient had only mild neurocognitive impairment [Gillis et al, ; Kline et al, ]. The Sanger sequencing identified a c.6,647A>G mutation in NIPBL , which resulted in the change of a highly conserved amino acid p. (Tyr2,216Cys) [Baquero‐Montoya et al, ].…”

Section: Special Casesmentioning

confidence: 99%

“…From the clinical standpoint, body asymmetries are usually indicators of somatic mosaicism [Youssoufian and Pyeritz, ], but, in this case, pyrosequencing studies ruled out a mosaic mutation. In addition, the finding of hypoplasia of the tibia and agenesis of fibula prompted the complementary studies, such as full exome, CGH‐Array, and MLPA (Multiplex ligation‐dependent probe amplification), which excluded the involvement of other potential causative genes [Baquero‐Montoya et al, ].…”

Section: Special Casesmentioning

confidence: 99%

“…Furthermore, phenotypic variations are so wide that patients with mutations in still unknown causal genes remain undiagnosed. In this paper, we describe some of atypical cases studied by our group [Wierzba et al, ; Baquero‐Montoya et al, ,,; Gil‐Rodríguez et al, ]. We hope this knowledge will help to expand the clinical boundaries of CdLS and contribute to facilitate its diagnosis.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Special cases in Cornelia de Lange syndrome: The Spanish experience

Pié¹,

Puisac²,

Hernández-Marcos³

et al. 2016

American J of Med Genetics Pt C

Self Cite

View full text Add to dashboard Cite

Cornelia de Lange Syndrome (CdLS) is an autosomal dominant (NIPBL, SMC3, and RAD21) or X-linked (SMC1A and HDAC8) disorder, characterized by distinctive craniofacial appearance, growth retardation, intellectual disability, and limb anomalies. In 2005, the Spanish CdLS Reference Center was started and now we have more than 270 cases in our database. In this special issue, we describe some of the unique or atypical patients studied by our group, whose clinical features have contributed to the expansion of the CdLS classical phenotype, helping clinicians to diagnose it. We include the case of a male with unilateral tibial hypoplasia and peroneal agenesis who had a mutation in NIPBL; we also describe one patient with a mutation in NIPBL and somatic mosaicism identified by new generation sequencing techniques; we also include one patient with CdLS and Turner syndrome; and last, an interesting patient with a duplication of the SMC1A gene. Finally, we make a short review of the splicing mutations we have found in NIPBL regarding the new knowledge on the physiological variants of the gene. © 2016 Wiley Periodicals, Inc.

show abstract

Section: Special Casesmentioning

confidence: 99%

Section: Special Casesmentioning

confidence: 99%

Section: Special Casesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Special cases in Cornelia de Lange syndrome: The Spanish experience

Pié¹,

Puisac²,

Hernández-Marcos³

et al. 2016

American J of Med Genetics Pt C

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent reports have indicated that 17p13.3 duplications should be considered the commonest cause of SHFM/ SHFLD [7–14]. In particular, Klopocki et al [9] scrutinized the minimal critical region (11.8 kb) by analyzing 17 families with 17p13.3 duplications, and identified BHLHA9 [which encodes basic helix–loop–helix (bHLH) family member A9] as a novel SHFM/SHFLD-related gene.…”

Section: Introductionmentioning

confidence: 99%

Bhlha9 regulates apical ectodermal ridge formation during limb development

et al. 2017

View full text Add to dashboard Cite

Split hand/foot malformation (SHFM) and SHFM combined with long-bone deficiency (SHFLD) are congenital dysgeneses of the limb. Although six different loci/mutations (SHFM1-SHFM6) have been found from studies on families with SHFM, the causes and associated pathogenic mechanisms for a large number of patients remain unidentified. On the basis of the identification of a duplicated gene region involving BHLHA9 in some affected families, BHLHA9 was identified as a novel SHFM/SHFLD-related gene. Although Bhlha9 is predicted to participate in limb development as a transcription factor, its precise function is unclear. Therefore, to study its physiological function, we generated a Bhlha9-knockout mouse and investigated gene expression and the associated phenotype in the limb bud. Bhlha9-knockout mice showed syndactyly and poliosis in the limb. Moreover, some apical ectodermal ridge (AER) formation related genes, including Trp63, exhibited an aberrant expression pattern in the limb bud of Bhlha9-knockout mice; TP63 (Trp63) was regulated by Bhlha9 on the basis of in vitro analysis. These observations suggest that Bhlha9 regulates AER formation during limb/finger development by regulating the expression of some AER-formation-related genes and abnormal expression of Bhlha9 leads to SHFM and SHFLD via dysregulation of AER formation and associated gene expression.

show abstract

Complex nutritional deficiencies in a large cohort of Italian patients with Cornelia de Lange syndrome spectrum

Parma

Cianci

Decimi

et al. 2020

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Cornelia de Lange syndrome Spectrum (CdLSp) is characterized by intellectual disability, facial dysmorphisms, and growth impairment. Although eating difficulties are a well‐known feature of the disease, there is no data regarding the nutritional deficiencies of these patients. The food intake was tracked using a dietary transcription provided by the family/caregivers, biochemical nutritional parameters were measured with laboratory tests and through an accurate clinical evaluation of the incidence of qualitative and quantitative imbalances in a cohort of 73 patients with CdLSp ware determined. Of these 73, 62 (85%) subjects provided a complete and detailed dietary transcription. In the studied population, a quantitative caloric imbalance in 47/62 (76%) subjects was observed. The caloric intake was low in 27/62 (43%) subjects whereas excessive in 20/62 (33%). Only 15/62 (24%) had an optimum caloric intake. Regarding micronutrients, a calcium intake deficiency in 32% of the patients (20/62) was observed. Blood tests revealed a low iron level in 22/73 (30%) of the patients and 25(OH)D deficiency in 49/73 (67%). Serum hypocalcemia was not evidenced. Qualitative and quantitative imbalances resulted in more frequent than expected in CdLSp patients. A qualitative imbalance was more prevalent in younger patients while in older patients prevailed mainly a quantitative disproportion. We found no statistically meaningful correlation between dietary imbalances, genetic, or clinical parameters. Our findings highlight the need for further studies to evaluate the basal metabolic rate of CdLSp patients and find a correlation with their growth impairment.

show abstract

Severe ipsilateral musculoskeletal involvement in a Cornelia de Lange patient with a novel NIPBL mutation

Cited by 8 publications

References 21 publications

Special cases in Cornelia de Lange syndrome: The Spanish experience

Special cases in Cornelia de Lange syndrome: The Spanish experience

Bhlha9 regulates apical ectodermal ridge formation during limb development

Complex nutritional deficiencies in a large cohort of Italian patients with Cornelia de Lange syndrome spectrum

Contact Info

Product

Resources

About