■遗传性低镁血症伴继发性低钙血症(HSH)是一种罕见的常染色体隐性遗传性疾病,原因是双等位基因TRPM6突变。尽管TRPM6突变引起的HSH的报道并不十分罕见,先前报告的HSH病例的发病年龄<1岁.
■我们收集并分析了发病年龄超过1岁的双胞胎兄弟的临床数据,并对患者及其父母进行了全外显子组测序。经Sanger测序确认,错义突变进行了分析。我们还搜索了Pubmed,并从病例报告和病例系列中提取临床数据,报告TRPM6突变患者的原始数据。
■双胞胎患者具有典型的HSH表型,具有新的TRPM6复合突变,p.T87K和c.705dupT,从他们的父亲和母亲那里继承下来,分别。T87是一个高度保守的位点,预计T87K会导致氢键破坏。我们确定了2002年5月28日至2021年12月31日发表的26篇文章,共报道了88例TRPM6突变患者。我们发现最常见的临床表型是低镁血症,低钙血症,和抽搐。然而,HSH患者的发病年龄几乎总是发生在12个月以下,我们研究的双胎患者发病年龄分别为18个月和26个月.
■我们在中国HSH家族中发现了两个新的TRPM6突变,并显示TRPM6中c.704c-c.705(exon7)insT和c.260(exon4)C>A突变的发病年龄比其他突变晚得多,并且严重程度要小得多。
UNASSIGNED: Hereditary hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disease due to biallelic TRPM6 mutations. Although the
reports of HSH caused by TRPM6 mutations are not very rare, the age of onset in previously reported HSH cases were <1 year.
UNASSIGNED: We collected and analyzed the clinical data of twin brothers with onset age over 1 year old and performed whole exome sequencing in the patients and their parents. Confirmed by Sanger sequencing, missense mutation was analyzed in silico. We also searched Pubmed, and extracted clinical data from
case reports and
case series with full text in English, reporting original data of patients with TRPM6 mutations.
UNASSIGNED: The twin patients had canonical HSH phenotype with compound novel TRPM6 mutations, p.T87K and c.705dupT, inherited from their father and mother, respectively. T87 is a highly conserved site and T87K is predicted to cause hydrogen bond disruption. We identified 26 articles published between May 28, 2002 to December 31, 2021 which reported a total of 88 patients with TRPM6 mutation. We found that the most common clinical phenotypes were hypomagnesemia, hypocalcemia, and convulsions. However, the age of onset in HSH patients almost always occurred under 12 months old, the twin patients of our study were 18 and 26 months old at onset.
UNASSIGNED: We identified two novel TRPM6 mutations in a Chinses family with HSH, and showed that the age of onset with c.704c-c.705(exon7)insT and c.260(exon4)C>A mutation in TRPM6 was much later than other mutations and would be much less serious.