ABSTRACT
Cornelia de Lange syndrome (CdLs), which is also called Brachmann de Lange syndrome, is a congenital disorder characterized by distinctive facial features, prenatal and postnatal growth deficiency, feeding difficulties, psychomotor delay, behavioral problems, and associated malformations that mainly involve the upper extremities. The prevalence ranges from 1:100,000 to as high as 1:10,000. Most cases (50-60%) were carried mutation in NIPBL gene. To our knowledge this is the first CdLs Indonesian case that reported with molecular analysis study. We present an 11 months old female Indonesian patient with classic CdLs with congenital hypothyroid. Genetics studies were performed in intron 1, exon 2, exon 10 and exon 22 of NIPBL gene. Thyroid studies (T3, T4, TSH and thyroid scan) were performed. Low level of T3 and T4, and high level of TSH were observed. Thyroid agenesis was found in thyroid scan examination. We detected thyroid agenesis which has been never reported in CdLs patients. We could not find any mutation in intron 1, exon 2, exon 10 and exon 22 of NIPBL gene. Further genetics examinations were necessary whether there is mutation in other locus.
Subject(s)
Congenital Hypothyroidism/diagnosis , De Lange Syndrome/diagnosis , Thyroid Dysgenesis/diagnosis , Cell Cycle Proteins , Congenital Hypothyroidism/genetics , Congenital Hypothyroidism/pathology , De Lange Syndrome/genetics , De Lange Syndrome/pathology , Female , Gene Expression , Humans , Indonesia , Infant , Proteins/genetics , Proteins/metabolism , Thyroid Dysgenesis/genetics , Thyroid Dysgenesis/pathology , Thyrotropin/genetics , Thyrotropin/metabolism , Thyroxine/deficiency , Thyroxine/genetics , Triiodothyronine/deficiency , Triiodothyronine/genetics , Up-RegulationABSTRACT
Non-syndromic cleft palate only (NS CPO) is one of the most common congenital malformations that affect between 1 in 1000 - 2500 live births worldwide. The etiopathogenesis of clefts including NS CPO has been widely studied but is still poorly understood. NS CPO is considered to be a genetically complex, multifactorial disease. Based on several studies, mutations of TGFß3 gene emerged as the strong candidate gene associated with NS CPO. The purpose of this study was to analyze the relationship between the TGFß3 / SfaN1 gene variant and the risk of NS CPO in Indonesian patients. This study was case control design using samples from 31 NS CPO subjects and 35 control subjects. DNA was extracted from venous blood and the segment of TGFß3 gene/ SfaN1 were amplified by using polymerase chain reaction (PCR) technique, then digestion products by SfaN1 restriction enzyme which can detect locus of gene variant / polymorphism from restriction fragment length polymorphisms (RFLP) method were evaluated. The results indicated that the gene variant as substitution of base G into A was identified in TGFß3 gene and the frequency of heterozygous mutant GA genotype was 63,6% in NS CPO subjects and 36,4% in control subjects. The frequency of heterozygous mutant GA genotype was associated with increased risk of NS CPO (odds ratio (OR) = 2,260, 95% CI = 0,592 - 8,625). In conclusion, TGFß3 gene / SfaN1 polymorphism can be considered as the risk factor associated with NS CPO in Indonesian patients.
