Association of AHSG with alopecia and mental retardation (APMR) syndrome

Sailani, M. Reza; Jahanbani, Fereshteh; Nasiri, Jafar; Behnam, Mahdiyeh; Salehi, Mansoor; Sedghi, Maryam; Hoseinzadeh, Majid; Takahashi, Shinichi; Zia, Amin; Gruber, Joshua J.; Lynch, Janet Linnea; Lam, Daniel D.; Winkelmann, Juliane; Amirkiai, Semira; Pang, Baoxu; Rego, Shannon; Mazroui, Safoura; Bernstein, Jonathan A.; Snyder, M

doi:10.1007/s00439-016-1756-5

Cited by 15 publications

(17 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Exome capture, library preparation, and sequencing, as well as data analysis, were performed as previously described ( Reza Sailani et al 2017 ). Briefly, exome capture and library preparation were performed using the Agilent SureSelectXT HumanAllExon V5 (product no.…”

Section: Methodsmentioning

confidence: 99%

WISP3 mutation associated with pseudorheumatoid dysplasia

Sailani

Chappell

Inlora

et al. 2017

Cold Spring Harb Mol Case Stud

Self Cite

View full text Add to dashboard Cite

Progressive pseudorheumatoid dysplasia (PPD) is a skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness. Here we report genetic characterization of a consanguineous family segregating an uncharacterized from of skeletal dysplasia. Whole-exome sequencing of four affected siblings and their parents identified a loss-of-function homozygous mutation in the WISP3 gene, leading to diagnosis of PPD in the affected individuals. The identified variant (Chr6: 112382301; WISP3:c.156C>A p.Cys52*) is rare and predicted to cause premature termination of the WISP3 protein.

show abstract

Section: Methodsmentioning

confidence: 99%

WISP3 mutation associated with pseudorheumatoid dysplasia

Sailani

Chappell

Inlora

et al. 2017

Cold Spring Harb Mol Case Stud

Self Cite

View full text Add to dashboard Cite

show abstract

“…Only a few families have been identified and affected individuals are characterized by the absence of scalp hair, the absence of eyebrows and eyelashes, and variable intellectual disability. 13 In 1992, a subdivision into three groups of APMR syndrome was proposed depending on the association with microcephaly and epilepsy: 14,15 (1) APMR with microcephaly without epilepsy, (2) APMR without microcephaly, and (3) APMR with microcephaly and epilepsy. To date, variants in the gene coding for the ɑ-2-HS-glycoprotein (AHSG) have been reported in one consanguineous family, suggesting AHSG as a potential cause of APMR.…”

Section: Introductionmentioning

confidence: 99%

“…To date, variants in the gene coding for the ɑ-2-HS-glycoprotein (AHSG) have been reported in one consanguineous family, suggesting AHSG as a potential cause of APMR. 13 Moreover, three loci have been associated with APMR by linkage analyses: APMR1 (MIM 203650), APMR2 (MIM 610422), and APMR3 (MIM 613930) have been mapped to chromosomes 3q26.33-q27.3 (ref. 16 ), 3q26.2-q26.31 (ref.…”

Section: Introductionmentioning

confidence: 99%

Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome

Besnard

Sloboda

Goldenberg

et al. 2019

Genetics in Medicine

View full text Add to dashboard Cite

Purpose: Lanosterol synthase (LSS) gene was initially described in families with extensive congenital cataracts. Recently, a study has highlighted LSS associated with hypotrichosis simplex. We expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. It is a rare autosomal recessive condition characterized by hypotrichosis and intellectual disability (ID) or developmental delay (DD), frequently associated with earlyonset epilepsy and other dermatological features. Methods: Through a multicenter international collaborative study, we identified LSS pathogenic variants in APMR individuals either by exome sequencing or LSS Sanger sequencing. Splicing defects were assessed by transcript analysis and minigene assay. Results: We reported ten APMR individuals from six unrelated families with biallelic variants in LSS. We additionally identified one affected individual with a single rare variant in LSS and an allelic imbalance suggesting a second event. Among the identified variants, two were truncating, seven were missense, and two were splicing variants. Quantification of cholesterol and its precursors did not reveal noticeable imbalance. Conclusion: In the cholesterol biosynthesis pathway, lanosterol synthase leads to the cyclization of (S)-2,3-oxidosqualene into lanosterol. Our data suggest LSS as a major gene causing a rare recessive neuroectodermal syndrome.

show abstract

“…The combination of ID and alopecia has been reported before [11], but inherited as an autosomal recessive disorder [12]. Both Reza Sailani et al [13] and Besnard et al [14] have recently reported a rare neuroectodermal syndrome with total or partial absence of hair and variable ID. Most of the patients in those studies presented with congenital alopecia, in contrast, individuals from family 2 of our study developed alopecia later in their teens.…”

Section: Discussionmentioning

confidence: 98%

Novel clinical and genetic insight into CXorf56-associated intellectual disability

et al. 2019

View full text Add to dashboard Cite

Intellectual disability (ID) is one of most frequent reasons for genetic consultation. The complex molecular anatomy of ID ranges from complete chromosomal imbalances to single nucleotide variant changes occurring de novo, with thousands of genes identified. This extreme genetic heterogeneity challenges the molecular diagnosis, which mostly requires a genomic approach. CXorf56 is largely uncharacterized and was recently proposed as a candidate ID gene based on findings in a single Dutch family. Here, we describe nine cases (six males and three females) from three unrelated families. Exome sequencing and combined database analyses, identified family-specific CXorf56 variants (NM_022101.3:c.498_503del, p.(Glu167_-Glu168del) and c.303_304delCTinsACCC, p.(Phe101Leufs*20)) that segregated with the ID phenotype. These variants are presumably leading to loss-of-function, which is the proposed disease mechanism. Clinically, CXorf56-related disease is a slowly progressive neurological disorder. The phenotype is more severe in hemizygote males, but might also manifests in heterozygote females, which showed skewed X-inactivation patterns in blood. Male patients might present previously unreported neurological features such as epilepsy, abnormal gait, tremor, and clonus, which extends the clinical spectrum of the disorder. In conclusion, we confirm the causative role of variants in CXorf56 for an X-linked form of intellectual disability with additional neurological features. The gene should be considered for molecular diagnostics of patients with ID, specifically when family history is suggestive of X-linked inheritance. Further work is needed to understand the role of this gene in neurodevelopment and intellectual disability.

show abstract

Association of AHSG with alopecia and mental retardation (APMR) syndrome

Cited by 15 publications

References 34 publications

WISP3 mutation associated with pseudorheumatoid dysplasia

WISP3 mutation associated with pseudorheumatoid dysplasia

Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome

Novel clinical and genetic insight into CXorf56-associated intellectual disability

Contact Info

Product

Resources

About