Alagille syndrome with <i>de Novo</i> del(20) (p 11.2)

Teebi, Ahmad S.; Murthy, D. S. Krishna; Ismail, E. A. R.; Redha, A. A.

doi:10.1002/ajmg.1320420109

Cited by 23 publications

(15 citation statements)

References 9 publications

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“…Furthermore, none of the 36 genes affected by the deletion have been associated with sex development. These results, in conjunction with previous reports of hypomasculinized external genitalia in a patient with a ≥6 Mb deletion at 20p13-12.3 [15] and in a patient with a 20p11.2-pter deletion [16], indicate that the genomic interval spanning ∼2.7–4.7 Mb from the telomere (deleted in case 2 and in the two aforementioned patients) encompasses a novel causative gene for DSD (Fig. 3B).…”

Section: Discussionsupporting

confidence: 88%

Cryptic Genomic Rearrangements in Three Patients with 46,XY Disorders of Sex Development

et al. 2013

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Background46,XY disorders of sex development (46,XY DSD) are genetically heterogeneous conditions. Recently, a few submicroscopic genomic rearrangements have been reported as novel genetic causes of 46,XY DSD.Methodology/Principal FindingsTo clarify the role of cryptic rearrangements in the development of 46,XY DSD, we performed array-based comparative genomic hybridization analysis for 24 genetic males with genital abnormalities. Heterozygous submicroscopic deletions were identified in three cases (cases 1–3). A ∼8.5 Mb terminal deletion at 9p24.1–24.3 was detected in case 1 that presented with complete female-type external genitalia and mental retardation; a ∼2.0 Mb interstitial deletion at 20p13 was identified in case 2 with ambiguous external genitalia and short stature; and a ∼18.0 Mb interstitial deletion at 2q31.1–32 was found in case 3 with ambiguous external genitalia, mental retardation and multiple anomalies. The genital abnormalities of case 1 could be ascribed to gonadal dysgenesis caused by haploinsufficiency of DMRT1, while those of case 3 were possibly associated with perturbed organogenesis due to a deletion of the HOXD cluster. The deletion in case 2 affected 36 genes, none of which have been previously implicated in sex development.Conclusions/SignificanceThe results indicate that cryptic genomic rearrangements constitute an important part of the molecular bases of 46,XY DSD and that submicroscopic deletions can lead to various types of 46,XY DSD that occur as components of contiguous gene deletion syndromes. Most importantly, our data provide a novel candidate locus for 46,XY DSD at 20p13.

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Section: Discussionsupporting

confidence: 88%

Cryptic Genomic Rearrangements in Three Patients with 46,XY Disorders of Sex Development

et al. 2013

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“…The first report by Loiodice et al I19701 lacked detailed cytogenetic and clinical descriptions. Another 16 cases were reviewed by Anad et al [1990] and Teebi et al [1992]. Spinner et al [1994] described another interesting three cases of Alagille syndrome in a twogeneration family with a cytogenetically balanced translocation between chromosomes 2 and 20, and they concluded that the Alagille gene may be a single dominant ., Alagille syndrome; 0 , possible Alagille syndrome.…”

Section: Discussionmentioning

confidence: 99%

Alagille syndrome with interstitial 20p deletion derived from maternal ins(7;20)

Shu

Yang

et al. 1996

Am. J. Med. Genet.

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We present a 6‐year‐old Chinese boy with Alagille syndrome and an interstitial 20p deletion, with a karyotype of 46,XY,der(20)dir ins(7;20)(q11.23;p11.23p12.2 or p12.2p13)mat. He had a peculiar face and suffered from congenital heart disease, growth retardation, severe cholestasis, hepatosplenomegaly, and impaired renal function. The karyotype of his mother showed a balanced translocation, 46,XX,dir ins(7;20)(q11.23;p11.23p12.2 or p12.2p13), and her phenotype was normal. His dead elder brother was highly suspected as another victim of Alagille syndrome. The findings in the present family suggested that if Alagille syndrome is a single gene defect, the putative gene responsible for the syndrome would not be located at the insertion breakpoints but located within the deletion extent. © 1996 John Wiley‐Liss, Inc.

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“…Linkage analysis of a large family with AGS has allowed us to map the disorder between D20S59 and D20S65 at 20pll.2-p l 2, a region of the genome that carries a dele tion in some patients with AGS (Schnittger et al 1989;Zhang et al 1990;Legius et al 1990;Anad et al 1990;Teebi et al 1992;Desmaze et al 1992) and that harbours the breakpoint of a balanced translocation in patients from a single family (Spinner et al 1994). At present, our resuits do not permit a further refinement of the mapping of the AGS locus, because the segment of 20p that co-segregates with the disorder spans the minimal area of overlap of deletions and of the translocation breakpoint (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The aetiology of AGS is largely unknown. An interstitial deletion at chro mosome 20p l 1,2-p l 2 has been detected in a limited num ber of patients indicating that this chromosomal region encompasses a locus for AGS (Byrne et al 1986;Schnittger et al 1989;Zhang et al 1990;Legius et al 1990;Anad et al 1990;Teebi et al 1992;Desmaze et al 1992). This has been substantiated by the detection of a family in which a balanced translocation t(2 ;20) (q2L3;pl2) co-segregates with the AGS phenotype (Spin ner et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Localization of Alagille syndrome to 20p11.2-p12 by linkage analysis of a three-generation family

et al. 1995

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A bstract Alagille syndrome (AGS) or arteriohepatic dysplasia is a rare but well-defined clinical entity that is usually inherited as an autosomal dominant trait. A lim ited number of patients carry a deletion in chromosome 20p, with 20p 11.23-pi 2.2 as the area of minimal overlap. Recently, a family has been identified in which a balanced translocation with a breakpoint in 20p l 2 co-segregates with the AGS phenotype. Here, we report a three-genera tion family with AGS and in which the affected members have a normal karyotype. Linkage analysis was perfozTned with markers from the 20p candidate region. A lod score of Z=2.96 was obtained with D20S27 at no recombina tion. Combining D20S27 and D20S61 to a single highly informative locus resulted in a maximum lod score of Z -+ 3.56 at 0=0.0. Haplotype analysis positioned AGS between D20S59 and D20S65, markers that define an in terval of about 40 cM. Allelic loss was not observed for the tested markers and no abnormalities in the PAX1 can didate gene were detected. These findings demonstrate that the locus on chromosome 20p could be responsible for AGS in cytogenetically normal patients and argues for a general role of this locus in the aetiology of AGS.

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Alagille syndrome with de Novo del(20) (p 11.2)

Abstract: We report on an Arab boy with Alagille syndrome and a de novo deletion of the short arm of chromosome 20 with a 46,XY, del(20)(p11.2) chromosome constitution. Other reported cases are briefly reviewed.

Cited by 23 publications

References 9 publications

Cryptic Genomic Rearrangements in Three Patients with 46,XY Disorders of Sex Development

Cryptic Genomic Rearrangements in Three Patients with 46,XY Disorders of Sex Development

Alagille syndrome with interstitial 20p deletion derived from maternal ins(7;20)

Localization of Alagille syndrome to 20p11.2-p12 by linkage analysis of a three-generation family

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